Download CLINICAL CANCER ADVANCES

2017
CLINICAL CANCER ADVANCES
A S CO ’ s 1 2 t h A n n u a l R e p o r t o n P r o g r e s s Ag a i n s t C a n ce r
I N S I D E  A S C O N A M E S A DVA N C E O F T H E Y E A R
EDITORS
EXECUTIVE EDITORS
Harold Burstein, MD, PhD, FASCO, Dana-Farber Cancer Institute, Boston, MA
Don S. Dizon, MD, FACP, Massachusetts General Hospital, Boston, MA
SPECIALTY EDITORS
Jeanny B. Aragon-Ching, MD, FACP, INOVA Schar Cancer Institute, Fairfax, VA
Nancy N. Baxter, MD, St. Michael’s Hospital, University of Toronto, Toronto, Canada
E. Gabriela Chiorean, MD, University of Washington, Seattle, WA
Warren Allen Chow, MD, FACP, City of Hope, Duarte, CA
John Frederick De Groot, MD, University of Texas MD Anderson Cancer Center, Houston, TX
Steven Michael Devine, MD, Ohio State University, Columbus, OH
Steven G. DuBois, MD, Dana-Farber Cancer Institute, Boston, MA
Wafik S. El-Deiry, MD, PhD, FACP, Fox Chase Cancer Center, Philadelphia, PA
Andrew S. Epstein, MD, Memorial Sloan Kettering Cancer Center, New York, NY
John Heymach, MD, PhD, University of Texas MD Anderson Cancer Center, Houston, TX
Joshua Adam Jones, MD, MA, University of Pennsylvania Health Systems, Philadelphia, PA
Deborah Mayer, PhD, AOCN, ANP-BC, University of North Carolina/
Lineberger Comprehensive Cancer Center, Chapel Hill, NC
Rebecca A. Miksad, MD, Beth Israel Deaconess Medical Center, Boston, MA
Nathan A. Pennell, MD, PhD, Cleveland Clinic, Cleveland, OH
Michael S. Sabel, MD, FACS, University of Michigan, Ann Arbor, MI
Lynn Mara Schuchter, MD, FASCO, University of Pennsylvania, Philadelphia, PA
Nadine Tung, MD, Beth Israel Deaconess Medical Center, Boston, MA
Karen Marie Winkfield, MD, PhD, Wake Forest Baptist Medical Center, Winston-Salem, NC
Lori J. Wirth, MD, Massachusetts General Hospital, Boston, MA
ASCO PRESIDENT
Daniel F. Hayes, MD, FASCO, FACP, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI
ASCO PRESIDENT-ELECT
Bruce E. Johnson, MD, FASCO, Dana-Farber Cancer Institute, Boston, MA
CHIEF EXECUTIVE OFFICER
Clifford A. Hudis, MD, FASCO, FACP
CHIEF MEDICAL OFFICER
Richard L. Schilsky, MD, FASCO, FACP
ACKNOWLEDGEMENT
The editors would like to thank Lada Krilov, PhD, Senior Specialist, Science Writing,
for her work drafting this report.
Copyright © 2017 American Society of Clinical Oncology. All rights reserved.
TOC
TABLE OF CONTENTS
A MESSAGE FROM ASCO’S PRESIDENT2
EXECUTIVE SUMMARY3
ADVANCE OF THE YEAR: IMMUNOTHERAPY 2.09
u Progress With Immune Checkpoint Inhibitors
10
u Emerging Clues on Patient Selection
15
u Checkpoint Inhibitors Work Well Against Hypermutated Cancers 16
CANCER RISK, PREVENTION AND SCREENING 19
u Additional Genes Linked to Ovarian Cancer Risk
20
u Pancreatic
Cancer Susceptibility Genes identified,
and New Opportunities for Screening and Prevention
21
u Broader
Testing Uncovers Unexpected Cancer Predisposition
Gene Mutations
22
u Many Children With Cancer May Carry Hereditary Gene Mutations
22
u Daily Vitamin B Reduces Skin Cancer Risk 23
u New Understanding of Barriers to Cancer Screening Among Latinas
24
ADVANCES IN CANCER TREATMENT BEYOND IMMUNOTHERAPY 25
u Targeted Therapy
27
u Combined Modality Therapy
31
u Chemotherapy32
u New Concerns About Laparoscopic Rectal Cancer Surgery
33
u Longer Hormone Therapy Further Reduces Breast Cancer Recurrence
33
ADVANCES IN PATIENT CARE
u ASCO Advances Patient Care Through Precision Medicine and Big Data
u Better Way to Prevent Chemotherapy-Triggered Nausea
u Patient Self-Reporting of Symptoms Improves Care
u Patient Navigation Program Improves Compliance With Cancer Therapy
u Addressing Health Literacy in the Era of Precision Medicine
u Excellent
10-year Survival for Patients With Early Prostate Cancer,
Regardless of Treatment
35
36
37
37
38
39
40
ADVANCES IN TUMOR BIOLOGY41
u Melanoma Develops Through Successive Genetic Changes
42
u Therapeutic Options Expand With Precision Medicine Approaches
42
LOOKING TO THE FUTURE43
u Liquid Biopsies Help Personalize Cancer Therapy
43
u Expanding Targeted Therapy Options for Ovarian Cancer
45
u Cancer
Moonshot: Galvanizing a Renewed Commitment to
Conquering Cancer
46
REFERENCES47
APPENDIX
u Additional Notable Advances u ASCO
Clinical Practice Guidelines
INDEX OF ADVANCES BY CANCER TYPE
50
54
55
To view this report online and learn more about progress against cancer, visit ASCO.org/CCA.
This report was also published in the Journal of Clinical Oncology at ascopubs.org/journal/jco on February 1, 2017.
A MESSAGE FROM ASCO’S PRESIDENT
I am pleased to present Clinical Cancer Advances 2017, which highlights
the most promising advances in patient-oriented cancer research over
the past year. The report gives us an opportunity to reflect on what an
exciting time it is for cancer research and how swiftly our understanding
of cancer has improved.
One year ago, the White House announced the national Cancer
Moonshot program to accelerate progress against cancer. This shared
vision of progress has reinvigorated the research community, identified
new areas of scientific collaboration, and raised our ambitions regarding
what may be possible beyond the progress we have already made.
When I entered the field 35 years ago, I could not have imagined where we would be today. We can now detect
cancer earlier, target treatments more effectively, and manage adverse effects more effectively to enable patients
to live better, more fulfilling lives. Today, two of three people with cancer live at least 5 years after diagnosis, up
from roughly one of two in the 1970s.
This progress has resulted from decades of incremental advances that have collectively expanded our
understanding of the molecular underpinnings of cancer. There is no better current example of this than
ASCO’s 2017 Advance of the Year: Immunotherapy 2.0.
Over the last year, there has been a wave of new successes with immunotherapy. Research has proven this
approach can be effective against a wide range of hard-to-treat advanced cancers previously considered
intractable. Researchers are now working to identify biologic markers that can help increase the effectiveness
of treatment and determine who is most likely to benefit from immunotherapy. This knowledge will enable
oncologists to make evidence-based decisions so as many patients as possible might benefit from this new type
of treatment.
Each successive advance builds on the previous hard work of generations of basic, translational, and clinical
cancer researchers. Importantly, the advances described in this report would not have been possible without the
individuals who volunteered to participate in clinical trials as part of their treatment.
To turn the promising vision of a cancer moonshot into meaningful advances, we need sustained, robust
federal funding for continued research and innovation. Approximately 30% of the research highlighted in this
report was funded, at least in part, through federal dollars appropriated to the National Institutes of Health or the
National Cancer Institute. Without this federal investment—unique internationally in scale, duration, and impact for
decades—I fear we may lose the forward momentum needed to further the progress we see highlighted in
this report.
Federal lawmakers can further fuel progress by advancing initiatives that facilitate the use of big data to achieve
the common good of high-quality care for all patients. Such programs, like ASCO’s CancerLinQ, will rapidly
increase the pace of progress and dramatically expand the reach of treatment advances to the millions of patients
who are living with cancer today or who will do so in the future. This investment will yield medical, scientific,
economic, and societal benefits for years to come.
Much work still lies ahead. Many questions remain about how cancer develops and spreads and how best to treat
it. As you read through Clinical Cancer Advances 2017, I hope you are as inspired as I am by the gains the clinical
cancer research community has made over the past year and by the promise of a new era of advances just over
the horizon.
Daniel F. Hayes, MD, FASCO, FACP
ASCO President, 2016 to 2017
2
CLINICAL CANCER ADVANCES 2017
u EXECUTIVE SUMMARY
Cancer is one of the world’s most pressing health care challenges.
On the whole, research progress from one year to the next is incremental,
and true breakthroughs are exceptional. Nevertheless, every year brings new
knowledge and insights that help direct further research and ultimately improve
the outlook for patients with cancer. This report highlights the most important
clinical advances of 2016 and previews where cancer science is headed.
Accelerated by the National Cancer Act of 1971 and then by a responsive
research infrastructure and increasingly innovative regulatory environment,
cancer research today delivers new treatments to patients faster than
ever. In just 1 year’s time (from November 2015 through October 2016),
the US Food and Drug Administration (FDA) has approved 20 therapies
for more than a dozen different types of cancer (Table 1). An example of
this accelerating progress is cancer immunotherapy.
CLINICAL CANCER ADVANCES 2017
3
A hundred years in the making, cancer
immunotherapy is now a standard treatment
option for people with a growing number of
different cancers. In 2016 alone, the FDA approved
immunotherapies for advanced forms of lung,
kidney, bladder, and head and neck cancers, as
well as Hodgkin lymphoma.
For some people with these advanced-stage
cancers, the advent of cancer immunotherapy
is truly life changing. It often offers the only
chance to live longer and better. And many
believe that this first wave of success with cancer
immunotherapy is just the beginning.
Building on our initial success, a key next step
is to understand why fewer than half of patients
currently selected for treatment actually benefit
from immunotherapy and why the benefit, if it
occurs, may be short lived. In 2016, several reports
revealed early insights into patient and cancer
characteristics (ie, biomarkers) that might predict
whether immunotherapy could work well in an
individual patient. For example, it seems that for
some cancers, the subset of tumors with many
genetic mutations can be more responsive to
current immunotherapy options.
While we are trying to identify who will
benefit, we are also exploring whether combining
immunotherapy treatments with one another or
with other cancer treatments, such as radiation
therapy and chemotherapy, might extend
Cancer by the Numbers
the impact of this new group of therapies.
Together, these efforts mark the next phase of
immunotherapy: Immunotherapy 2.0: Expanding
Use and Refining Patient Selection, the American
Society of Clinical Oncology’s (ASCO) Advance of
the Year.
PRECISION MEDICINE
The advances highlighted in this report attest to
a key trend that is driving progress against cancer
today: cancer therapies are becoming increasingly
precise, thereby enabling a more personalized
approach to treatment selection. The research into
cancer biology is propelling rapid development of
novel treatments targeting the key molecules that
allow cancers to grow and spread. In 2016 alone,
this strategy resulted in new targeted therapies
for people living with advanced cancers of the
lung, breast, and kidney, as well as several hardto-treat forms of blood cancer.
Today, new molecular technologies can quickly
pinpoint molecular changes in the tumor or
free-floating cancer DNA in the blood. For a
growing number of patients, such changes can be
matched to either existing targeted treatments
or experimental treatments that are being tested
in clinical trials. Although this approach is not
yet routine, early research suggests it could open
viable new treatment options for patients with a
wide range of hard-to-treat cancers (as described
in Looking to the Future).
22M
70%
u
WHAT’S NEXT FOR CANCER
IMMUNOTHERAPY?
The World Health Organization projects that the number of new cancer diagnoses will reach 22
million per year in the next two decades, up from 14 million in 2012. In the same timeframe, cancerrelated deaths may increase by as much as 70%. Seven of 10 deaths resulting from cancer occur
in Africa, Asia, and Central and South America, regions of the world with limited access to cancer
screening and treatment.1
In the United States, an estimated 1.7 million people were diagnosed with cancer in 2016.2 Because of
the growing population of older adults and changing demographics, US annual cancer incidence is
expected to reach 2.2 million per year by 2030.3
The good news is that, for most people, a diagnosis of cancer is not as grim as it used to be. Today,
68% of adults and 81% of children with cancer will be alive at least 5 years after a diagnosis. This is
a big improvement from the 1970s, when only 50% of adults and 62% of children were surviving 5
years.4 Although annual US cancer death rates have been declining in the last 20 years, the number
of deaths resulting from cancer remains high because of overall population growth.
Stewart BW, Wild CP (eds): World Cancer Report 2014. Lyon, France, IARC Press, 2014
1
American Cancer Society: Cancer Facts and Figures 2016. http://www.cancer.org/acs/groups/content/@research/documents/
document/acspc-047079.pdf
2
Rahib L, Smith BD, Aizenberg R, et al: Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and
pancreas cancers in the United States. Cancer Res 74:2913-21, 2014
3
National Institutes of Health: Fact Sheet: Cancer. https://report.nih.gov/nihfactsheets/viewfactsheet.aspx?csid575
4
4
CLINICAL CANCER ADVANCES 2017
CARING FOR THE WHOLE PATIENT
FEDERAL FUNDING SUPPORTS
PIONEERING RESEARCH
In the 21st century, people with cancer are not
only living longer than ever, but also enjoying
Clinical cancer research in the United States is
a better quality of life than before. Indeed, an
made possible through funding from both public
entire field of cancer survivorship has emerged—
and private sectors. When it comes to high-risk,
studying ways to improve life as well as extend
pioneering research, federal funding is often
it. Although treating the physical illness remains
indispensable and has been a unique asset over
a priority, more and more attention is being paid
the decades since World War II. Often only federal
to caring for the whole patient, which includes
funding can support research that the private
his or her emotional and
sector typically does
psychosocial needs.
not pursue, such as
With increased access
cancer prevention and
to health information,
screening and treatment
patients today can be
comparisons.
more active partners
Funding from the US
in their health care. A
National Institutes of
patient’s values and
Health (NIH) supported
preferences are critical
approximately one-third
when it comes to
of the top advances
U.S. Representative Tom Cole (R-OK)
decisions about cancer
highlighted in this
Chairman of the
screening and prevention
report. Among the most
House Subcommittee on Labor,
measures, as well as
notable are:
Health and Human Services, Education
cancer therapy selection.
XX
Early evidence that
and Related Agencies
Indeed, lifestyle and
immunotherapy is
environmental factors
effective against
along with genomics
an aggressive,
Cancer touches all Americans. At its core,
represent the keys to
nonmelanoma
funding for cancer research reflects the
precision medicine.
skin cancer
This report features
XXA new, life-extending
American values that support innovation
efforts to ensure that
targeted treatment
and research breakthroughs that improve
every patient with
of an aggressive
and save lives. A regular, manageable and
cancer receives the best
blood cancer
predictable investment in the NIH and the
possible care. Among
XXImproved therapies
National Cancer Institute will allow the
these efforts are Webfor children
scientific
community to plan for the future
based tools for selfwith high-risk
monitoring symptoms,
neuroblastoma and
and make progress against cancer and other
education and
adults with glioma
life-shortening diseases.
navigation programs for
XXFirst insight into how
underserved populations,
genetic changes
and a better way to
evolve during the
prevent nausea triggered by chemotherapy. Lastly,
development of
this report reviews clinical research addressing a
melanoma
long-standing unresolved question in a common
XXDiscovery of two genes linked to increased risk
malignancy: prostate cancer.
of ovarian cancer
XXIdentification of heritable genetic mutations
in children with cancer and people with
suspected Lynch syndrome
XXApplications of liquid biopsy testing in
cancer care
“
”
ASCO is calling on lawmakers to continue to build on investments
in NIH and NCI with predictable and sustainable future funding
increases to meet the promise of today’s research.
CLINICAL CANCER ADVANCES 2017
5
Fig 1. Robust federal funding needed to accelerate cancer research.
FEDERAL FUNDING IS CRITICAL TO
ADVANCING OUR NATION'S CANCER PROGRESS
People with cancer are living better and longer,
thanks to our nation's investment in cancer research
DECLINE IN CANCER
DEATH RATE
Since a peak in 19911
CANCER DRUGS
APPROVED BY
THE FDA SINCE
2006²
14.5M
CANCER
SURVIVORS
INCREASED
5-YEAR SURVIVAL
Up from 11.4 million in 20061
2 out of 3 people with
cancer live at least 5
years after diagnosis1
Yet, while the NIH received its
first significant budget increase
in over a decade in 2016...
NCI’s budget, when adjusted
for inflation, remains below
prerecession levels3
FUNDING FOR NCI RESEARCH3
6.0
DOLLARS IN BILLIONS
23%
5.0
4.0
3.0
2.0
1.0
NOMINAL
INFLATION ADJUSTED
0.0
1998
2000
2002
2006
2004
2008
2010
2012
2014
2016
FISCAL YEARS
NIH = National Institutes of Health NCI = National Cancer Institute
Source: National Cancer Institute
Increased federal funding is urgently needed to accelerate
life-saving research and new cancer breakthroughs
Current research priorities include:4,5
IMMUNOTHERAPY
RESEARCH
ENHANCED
DATA SHARING
Support mechanisms to
identify, test and validate
new predictive biomarkers
Create a national
ecosystem for sharing
and analyzing data
EXPANDED PREVENTION
AND DETECTION
STRATEGIES
Boost prevention research
and increase testing to
identify high-risk patients
Millions of Americans living with cancer and their loved ones
are waiting for new breakthroughs
ASCO calls on Congress to build on critical investments
by increasing funding to the NIH and NCI.
For more information visit asco.org/nihfunding.
Sources: 1. American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 2016. 2. U.S. Food and Drug Administration. Approved Drugs – Oncology Drugs. Available at: http://www.fda.gov/Drugs/InformationOnDrugs/
ApprovedDrugs/ucm279174.htm. Accessed on October 7, 2016. 3. National Cancer Institute. NCI Budget and Appropriations. Available at: https://www.cancer.gov/about-nci/budget. Accessed on October 7, 2016. 4. The White House. Fact Sheet:
Investing in the National Cancer Moonshot. Available at: https://www.whitehouse.gov/the-press-office/2016/02/01/fact-sheet-investing-national-cancer-moonshot. Accessed on October 7, 2016. 5. Hayes, Daniel F., MD. "Request for
Recommendation of Immediate Actions for the National Cancer Moonshot." Letter to The Vice President. 6 Sept. 2016. MS. Alexandria, VA
6
CLINICAL CANCER ADVANCES 2017
Sustained and steady funding of the NIH
and National Cancer Institute (NCI) is critical to
maintaining the pace of scientific discovery and
continued progress against cancer. However,
although the NIH received its first budget increase
in more than a decade in 2016, the budget of the
NCI, when adjusted for inflation, remains below
prerecession levels (Fig 1). Failure to sustain the
historic US investment in research places health
outcomes, scientific leadership, and economic
growth at risk.
ABOUT CLINICAL CANCER ADVANCES
ASCO developed this annual report, now in its
12th year, to document the important progress being
made in clinical cancer research and highlight
emerging trends in the field. Clinical Cancer
Advances serves to outline to the public progress
achieved in clinical cancer research and care each
year. As a whole, this document attests to the
exciting current state of the science and envisions
future directions of cancer research.
The content of Clinical Cancer Advances was
developed under the direction of a 20-person
editorial board composed of experts in a wide range
of oncology subspecialties. The editors reviewed
research reports published in peer-reviewed
scientific and medical journals or presented at major
scientific meetings over a 1-year period (October
2015 to October 2016). The advances highlighted in
this report cover the full range of clinical research
disciplines: prevention, treatment, patient care, and
tumor biology.
ABOUT THE AMERICAN SOCIETY
OF CLINICAL ONCOLOGY
ASCO Advocacy Summit
Spotlights Need for Action
on Cancer Policy
Volunteer advocates from across the United
States participated in the first annual ASCO
Advocacy Summit to urge Congress to take
action on critical policies that would advance
cancer research and treatment and ensure
that the 14.5 million patients with cancer and
survivors of cancer have access to high-quality,
high-value health care.
Through in-person meetings and letters to
members of Congress, ASCO volunteers asked
lawmakers to support policies to advance data
sharing, increase funding for medical research,
and ensure patient access to necessary cancer
treatment, among other issues.
XXFor more information on ASCO’s policy
statements and advocacy initiatives,
visit ascoaction.asco.org.
Founded in 1964, ASCO is committed to making
a world of difference in cancer care. As the world’s
leading organization of its kind, ASCO represents
more than 40,000 oncology professionals who care
for people living with cancer. Through research,
education, and promotion of the highest-quality
patient care, ASCO works to conquer cancer and
create a world where cancer is prevented or cured,
and every survivor is healthy. ASCO is supported
by its affiliate organization, the Conquer Cancer
Foundation. Learn more at ASCO.org, explore patient
education resources at Cancer.Net, and follow us on
Facebook, Twitter, LinkedIn, and YouTube.
ASCO has created a badge to highlight
research that has received federal funding.
Studies in this report that have received federal
funding are denoted with this badge.
XXFor more information, please visit
asco.org/nihfunding.
CLINICAL CANCER ADVANCES 2017
7
THE CONQUER CANCER
FOUNDATION
The Conquer Cancer Foundation was created by
the world’s foremost cancer physicians of ASCO
to seek dramatic advances in the prevention,
treatment, and cure of all types of cancer. Toward
the vision of a world free from the fear of cancer, the
foundation works to conquer this disease by funding
breakthrough cancer research, sharing cutting-edge
knowledge with patients and physicians worldwide,
and by improving quality of care and access to care,
enhancing the lives of all who are touched by cancer.
Over 33 years, more than $105 million in funding
has been provided through the Conquer Cancer
Foundation Grants and Awards Program to support
clinical and translational scientists at all levels of
their careers, working around the globe to address
the full spectrum of oncology—from prevention
through survivorship and end-of-life care. The
foundation has given more than 1,700 grants and
awards in 68 countries. Foundation grants have
helped researchers launch successful careers and
make discoveries that benefit patients with cancer.
Several of the studies featured in this year’s
Clinical Cancer Advances report were led by past
Conquer Cancer Foundation grant recipients who
have continued their careers in oncology research.
8
CLINICAL CANCER ADVANCES 2017
u A
DVANCE OF THE YEAR:
IMMUNOTHERAPY 2.0
E X PA N D IN G U S E A N D RE FINING PATIENT S E LE CTIO N
This year, ASCO has named Immunotherapy 2.0 as the advance
of the year. This selection recognizes the growing wave of progress using
cancer immunotherapy, which has extended and improved the lives of
patients, many of whom had few other effective treatment options.
It has taken scientists more than a century to learn how to harness the
immune system to fight cancer. A number of strategies to achieve this
have been tried, but one approach—blocking immune checkpoints—has
been particularly effective against a range of different cancers. Immune
checkpoints are specialized proteins that act as brakes on the immune
system, ensuring that immune defenses are engaged only when they are
needed and for as long as they are needed. They prevent the immune
system from becoming overactive, which can lead to excessive inflammation
or autoimmune disease.
CLINICAL CANCER ADVANCES 2017
9
Fig 2. Immune checkpoint inhibitors: releasing the brakes on the immune system.
When a cancer cell encounters a T cell (a type of
immune cell), the interaction between the major
histocompatibility complex (MHC) and the T-cell
receptor (TCR) molecules activates the T cell.
But when the PD-L1 checkpoint protein on the
cancer cell attaches to the PD-1 checkpoint
receptor on the T cell, the T cell is deactivated.
New immune checkpoint inhibitor therapies
prevent the PD-L1 checkpoint protein from
attaching to the PD-1 checkpoint receptor.
This allows the MHC and TCR interaction
to activate the T cell and unleash the
immune system to attack cancer.
TCR
MHC
T cell
Deactivated
T cell
Activated
Cancer Cell
Cancer Cell
PD-1
PD-L1
PD-1 Checkpoint
Inhibitor
PD-L1 Checkpoint
Inhibitor
Cancer treatments known as immune checkpoint
inhibitors unleash the immune system to attack
cancer (Fig 2). Since the first remarkable reports
of immune checkpoint inhibitors shrinking
advanced melanoma in 2011, research in this area
has taken off at an incredible pace. Over the past
year, the FDA approved five new uses for immune
checkpoint inhibitors: lung cancer, head and neck
cancer, bladder cancer, kidney cancer, and Hodgkin
lymphoma. However, many other patients with the
same types of cancer either do not benefit from
immunotherapy at all or experience a benefit that
is short lived. New research reported in 2016 is
advancing the ability to identify patients who
are most likely to benefit from immunotherapy,
while sparing others from its high cost and
adverse effects.
PROGRESS WITH IMMUNE
CHECKPOINT INHIBITORS
Immunotherapy extends
long-term survival in
advanced melanoma.
The number of people
diagnosed with melanoma
has risen sharply over the
last three decades and
is continuing to increase
worldwide. In 2016, an
10
CLINICAL CANCER ADVANCES 2017
estimated 76,380 adults in the United States were
diagnosed with melanoma of the skin.1 Melanoma is
the fifth most common cancer among men and the
seventh most common cancer among women.
Although it accounts for only 1% of all skin
cancers, melanoma causes the vast majority of
deaths resulting from skin cancer. It is estimated
that 10,130 deaths resulting from melanoma
occurred last year.1
Most people with melanoma are cured with
surgery alone. However, among patients with
metastatic melanoma, only 17% will live 5 years after
their diagnosis.
In just a few short years, immunotherapy has
transformed the outlook for this disease. Given
the lasting responses seen in a large proportion of
patients who have received immunotherapy, experts
are beginning to speculate that a cure may be within
reach, at least for a fortunate few patients.
Approval of the checkpoint inhibitor ipilimumab
marked the first treatment that could prolong life
for patients with advanced melanoma (ipilimumab
blocks the immune checkpoint cytotoxic T-cell
lymphocyte-4 [CTLA-4]). By the end of 2014, the
FDA had approved two additional checkpoint
inhibitors for use in patients with advanced
melanoma: pembrolizumab and nivolumab. In
research studies, both proved to be even more
effective than ipilimumab, while causing fewer
adverse effects.
In 2016, researchers reported findings from the
long-term follow-up of 655 patients enrolled in an
early clinical trial of pembrolizumab.2 The median
survival was 23 months, and the 24-month survival
rate was 49%. Tumors shrunk in one-third of the
patients, and treatment responses lasted more than
1 year in 44%. Pembrolizumab was generally well
tolerated, with severe adverse effects occurring in
only 14% of patients. The most common adverse
effects included fatigue, itchiness, and rash.
The findings are similar to those previously
reported for nivolumab, which yielded a 24-month
survival rate of 43% among patients with advanced
melanoma.3 By comparison, an earlier analysis of
pooled data from several trials of ipilimumab found
a median survival of only 11.4 months.4 Ongoing
studies are exploring combinations of different
checkpoint inhibitors, which seem to work better
than one checkpoint inhibitor alone, although they
produce more adverse effects.5
Meanwhile, a large clinical trial found that
adjuvant immunotherapy can also help extend life
for patients who have stage III melanomas that
can be surgically removed.6 Despite successful
surgery, a majority (approximately 60%) of such
patients will experience a recurrence of melanoma
within 4 years of removal. In the study, patients
who had undergone surgery that completely
removed the cancer were randomly assigned to
receive ipilimumab or placebo. The 5-year survival
rate was 65% in the ipilimumab group and 54% in
the placebo group. Immunotherapy helped reduce
the recurrence of melanoma and metastasis (ie,
spreading to distant parts of the body). At 5 years,
more patients in the ipilimumab group had not yet
experienced a recurrence (41% v 30%) or metastasis
(48% v 39%).
Of note, the dose of ipilimumab was
approximately three times higher than the
FDA-approved dose for this patient population (10
mg/kg v 3 mg/kg). This higher dose was chosen
on the basis of earlier research showing that the
higher dose may be more effective, although it does
result in more adverse effects. In this study, 54%
of patients experienced a severe adverse effect,
and five (1%) died as a result of treatment-related
adverse effects.
These findings suggest that high-dose ipilimumab
may help patients with stage III melanoma live
longer after surgery. However, the adverse effects
of this treatment are common and can be life
threatening. Benefits and risks for each individual
patient will have to be weighed carefully in
treatment-decision discussions.
Programmed death-1
inhibitors help people with
advanced lung cancer live
longer. Lung cancer is the
most common cancer
worldwide, with 1.8 million
new diagnoses in 2012. It
is also the leading cause
of cancer-related death,
taking a staggering 1.6
million lives each year. This is equivalent to three
people dying every minute.7
Non–small-cell lung cancer (NSCLC) accounts for
the great majority (85%) of all lung cancers. People
with advanced NSCLC have a grim prognosis. Until
the approval of the programmed death-1 (PD-1)
checkpoint inhibitors pembrolizumab and nivolumab in 2015, the median life expectancy with
standard chemotherapy was only 10 months.
In 2016, researchers reported findings from a
large trial comparing pembrolizumab with standard
docetaxel chemotherapy in patients with previously
treated, advanced, programmed death ligand-1
VOICES OF CANCER RESEARCH
REBECCA HILL
In 2014, Rebecca found out that the lung cancer that she had been
previously diagnosed with had returned and spread to other areas. Her
doctors quickly ran out of treatment options and suggested hospice.
“I’m in remission—
I can’t believe
it myself.”
It was then that Rebecca learned about a clinical trial investigating
a type of immunotherapy called nivolumab for advanced lung
cancer. After one month on the trial, her tumor began to shrink, and
the severe pain Rebecca had felt for the last year finally began to
subside. Today, the cancer is in remission.
Rebecca is an active participant in the #LCSM Twitter community and is
pictured left with her oncologist Katherine Wang, MD, PhD.
CLINICAL CANCER ADVANCES 2017
11
LUNG CANCER IS THE MOST COMMON CANCER WORLDWIDE
THE LEADING CAUSE OF CANCER-RELATED DEATH
1.8M
NEW DIAGNOSES
IN 2012
3 PEOPLE DYING EVERY
60 SECS
(PD-L1) –positive NSCLC.8 Among all patients
treated in the study, the median survival was 10.4
months with pembrolizumab versus 8.5 months
with docetaxel. In the group of patients with higher
levels of PD-L1 (at least 50% of cells positive for
PD-L1), the median survival with pembrolizumab
was even longer (14.9 v 8.2 months). In addition, the
rate of severe adverse effects was much lower with
pembrolizumab than with docetaxel (16% v 35%).
Not only does immunotherapy offer patients with
NSCLC the chance to live longer, it is also far easier
to tolerate than chemotherapy for many patients.
These findings established pembrolizumab as a
new standard option for patients with previously
treated, advanced NSCLC. The study also sparked a
national conversation about the importance of PDL1 biomarker testing to select patients who are most
likely to benefit from immune checkpoint inhibitors.
Meanwhile, findings from a large clinical trial
suggest that pembrolizumab may be more
effective than chemotherapy as an initial treatment
for patients who have metastatic NSCLC with
high levels of PD-L1 (> 50% of cancer cells are
PD-1 positive),9 whereas a similar study failed
to demonstrate superiority of nivolumab to
chemotherapy in this setting.10
These findings will change initial treatment of
metastatic NSCLC in that every newly diagnosed
patient will need to be tested for PD-L1. Patients
with high PD-L1 levels will likely receive immunotherapy rather than chemotherapy.
Another immune checkpoint inhibitor,
atezolizumab, was approved by the FDA in 2016
for patients with previously treated, metastatic
NSCLC.11 The approval was based on two large
clinical trials, which showed that patients who
received atezolizumab lived longer (13.8 and 12.6
months, respectively) than those who received
standard docetaxel chemotherapy (9.6 and 9.7
months, respectively). The most common adverse
effects related to treatment with atezolizumab
included fatigue, decreased appetite, shortness of
breath, cough, and nausea. Atezolizumab is a PDL1 inhibitor previously approved for treatment of
bladder cancer.
12
CLINICAL CANCER ADVANCES 2017
1.6M
LIVES LOST
EACH YEAR
In October 2016, the FDA approved pembrolizumab for use as first-line treatment for patients with
advanced, PD-L1–positive NSCLC.12 A breakthrough
therapy designation had previously been granted
for the same use. These studies collectively mean
that the historical standard treatment of advanced
lung cancer (ie, chemotherapy) has finally been
displaced by immunotherapy as either first- or
second-line treatment.
First new treatment for
bladder cancer in three
decades. An estimated
76,960 people were
diagnosed with bladder
cancer in the United States
in 2016, and 430,000 were
diagnosed worldwide in
2012.7,13 Bladder cancer is
more common among men
than women. In fact, bladder cancer is the fourth
most common cancer among men.
It is estimated that 16,390 deaths resulting
from bladder cancer occurred in the United States
in 2016. The most commonly diagnosed type of
bladder cancer is superficial bladder cancer (ie,
cancer that has not yet spread outside of the
bladder), which can typically be treated successfully.
However, people who have advanced bladder
cancer are in desperate need of better therapies.
Only 15% of patients with bladder cancer that has
spread to distant parts of the body live 5 years
after diagnosis.14 Cancer.Net provides details about
bladder cancer for patients, caregivers, and others
seeking reliable information.
There had been little progress in the treatment
of advanced bladder cancer for several decades
until the FDA approval of the immunotherapy
atezolizumab in May 2016.15 Atezolizumab was also
the first PD-L1 checkpoint inhibitor to gain FDA
approval for any use.
The approval of atezolizumab was based on an
early clinical trial of patients with previously treated
metastatic urothelial cancer, the most common
type of bladder cancer.16 Among patients with
bladder cancer that worsens after initial cisplatin- or
platinum-based chemotherapy, historical response
rates to chemotherapy have been poor, with tumors
shrinking in only approximately 10% of patients. In
contrast, the response rate to atezolizumab was
15% among all patients in the study and 27% in the
group of patients with more PD-L1–positive immune
cells.
Immunotherapy has played an important role
in the treatment of early bladder cancer since
1990, with the FDA approval of Bacillus CalmetteGuérin (BCG), a live bacterium related to cow
tuberculosis. BCG has been used as a vaccine to
prevent tuberculosis for more than a century. It
is not fully understood how BCG works against
bladder cancer, but many researchers think that
it triggers the immune system to destroy cancer
cells. The approval of atezolizumab has paved
the way for further investigation of checkpoint
inhibitors in bladder cancer, including a latestage trial comparing atezolizumab with standard
chemotherapy in patients with bladder cancer that
worsened after platinum-based chemotherapy
(ClinicalTrials.gov identifier: NCT02302807).
In 2016, researchers also reported promising early
findings from two clinical trials of pembrolizumab in
patients with advanced bladder cancer. In a latestage clinical trial, patients with previously treated
cancer who received pembrolizumab lived longer
than those who received chemotherapy.17 Another
clinical trial suggested that pembrolizumab may
also be effective as an initial (first-line) treatment for
patients with advanced bladder cancer who are not
eligible for cisplatin chemotherapy. Tumors shrunk in
24% of all patients treated in the study. In the group
of patients with high levels of PD-L1 in tumor and
immune cells, 37% experienced tumor shrinkage,
and 13% experienced a complete response.18
Pembrolizumab is also being tested in patients
with earlier-stage, superficial bladder cancers that
are resistant to BCG (ClinicalTrials.gov identifiers:
NCT02808143 and NCT02625961). Meanwhile,
another early study is exploring a different PD-L1
checkpoint inhibitor, avelumab, as a maintenance
therapy for patients with bladder cancer that did
not worsen after initial chemotherapy (ClinicalTrials.
gov identifier: NCT02603432).
Immunotherapy extends life
after head and neck cancer
recurrence. More than
600,000 people around
the world are diagnosed
with head and neck cancer
every year, with nearly
50,000 in the United States
alone.19,20 This type of
cancer is difficult to treat,
particularly if it recurs or spreads (ie, metastasizes).
Patients with squamous cell head and neck
cancer that worsens within 6 months of treatment
with chemotherapy have no life-extending
therapy options.
However, a recent clinical trial suggests that
nivolumab may offer such patients a chance to
live longer.21 The estimated 1-year survival rate was
more than two-fold higher among patients treated
with nivolumab than that among those treated with
standard chemotherapy (36% v 17%). The median
survival was 7.5 months in the nivolumab group and
5.1 months in the chemotherapy group.
Fewer patients in the nivolumab group (13% v
35%) had severe treatment-related adverse effects.
In addition, quality of life remained stable among
patients who received nivolumab but deteriorated
among those who received chemotherapy. Based on
the results of this trial, the FDA approved nivolumab
for the treatment of patients with recurrent or
metastatic squamous cell carcinoma of the head
and neck in November 2016.22
VOICES OF CANCER RESEARCH
SUSAN CORCORAN
When Susan’s bladder cancer returned in 2013, doctors told her
the cancer had spread, and treatment would only slow its growth
temporarily. Now, nearly four years later, Susan is cancer-free, thanks to
a clinical trial of an immunotherapy called atezolizumab.
“This clinical trial
saved my life.”
Susan has been on the trial for more than two years now, receiving an
infusion of atezolizumab once every three weeks. She has spent this
time traveling with her husband, dragon boating with fellow cancer
survivors, and visiting her grandchildren.
Susan is a member of the Bladder Cancer Advocacy Network (BCAN).
CLINICAL CANCER ADVANCES 2017
13
Ongoing clinical trials are exploring whether
combining nivolumab with ipilimumab may
further improve patient outcomes (ClinicalTrials.
gov identifiers: NCT02741570 and NCT02823574).
Meanwhile, pembrolizumab is already approved as
treatment for patients with recurrent or metastatic
head and neck cancer.
Chance to slow ovarian
cancer progression.
Compared with other
cancers, ovarian cancer is
relatively uncommon, with
an estimated 22,280 new
diagnoses in the United
States in 2016.23 Worldwide,
239,000 women were
diagnosed with ovarian
cancer in 2012.7
Nonetheless, ovarian cancer is the fifth most
common cause of cancer-related death among
US women, causing an estimated 14,240 deaths in
2016.23 Because of the lack of specific symptoms,
ovarian cancer has often reached an advanced
stage by the time of diagnosis. Despite surgery
and chemotherapy, more than 70% of women with
ovarian cancer that goes into remission eventually
experience a relapse. Fewer than half of such
women live 5 years after diagnosis.
Early research published in 2015 suggests
that nivolumab may help some women with
ovarian cancer that has relapsed after platinumbased chemotherapy. In an early clinical trial
of 20 women, three (15%) experienced tumor
shrinkage after treatment with nivolumab, and an
additional six (30%) had stable disease (ie, tumors
neither shrinking nor growing).24 Two women
experienced complete remission, one of whom had
a type of ovarian cancer particularly resistant to
chemotherapy (clear cell carcinoma).
These early findings have spurred further research
on how best to incorporate immunotherapy into the
treatment of ovarian cancer. Several ongoing clinical
trials are exploring nivolumab in combination with
other immunotherapies for women with recurrent
ovarian cancer (ClinicalTrials.gov identifiers:
NCT02737787, NCT02335918, and NCT01928394).
Hodgkin lymphoma seems
particularly susceptible to
PD-1 inhibitors. Hodgkin
lymphoma is a cancer of
the lymphatic system. It is
a fairly uncommon cancer,
with an estimated 8,500
people diagnosed in the
United States in 2016.25
Hodgkin lymphoma is
14
CLINICAL CANCER ADVANCES 2017
more common among young adults and men than it
is among women.
Classic Hodgkin lymphoma is the most common
type of Hodgkin lymphoma, accounting for 95%
of all cases. The survival rate for classic Hodgkin
lymphoma has been increasing for the past 40
years as a result of treatment improvements. Most
patients with classic Hodgkin lymphoma achieve
good outcomes with initial chemotherapy, and 86%
will live 5 years after diagnosis.
However, in approximately 20% to 30% of
patients, classic Hodgkin lymphoma will relapse
after initial treatment or will not respond to therapy
at all. Such patients require further, more intensive
treatment, such as high-dose chemotherapy
followed by autologous stem-cell transplantation
(ASCT). If the cancer relapses after ASCT, a
newer regimen combining a targeted drug with
chemotherapy, brentuximab vedotin, can extend
survival, but in many patients, the lymphoma
eventually worsens despite treatment.
Research reported in 2016 led to a new treatment
option for such patients: nivolumab.26 This advance
stems from an earlier discovery of genetic changes
in malignant classic Hodgkin lymphoma cells called
Reed-Sternberg cells. The genetic changes result
in an abundance of immune checkpoint molecules
PD-L1 and PD-L2, which help the cancer cells
dampen immune responses through the PD-1/PDL1 checkpoint. This insight suggests that classic
Hodgkin lymphoma may be particularly susceptible
to PD-1 and PD-L1 immune checkpoint inhibitors.
A recent analysis of biopsy samples from newly
diagnosed patients with classic Hodgkin lymphoma
showed that the genetic changes that lead to an
abundance of PD-L1 and PD-L2 markers (polysomy,
copy gain, and amplification) are extremely
common.27 Such genetic changes were found in
97% of the 108 specimens tested. This genetic
underpinning maybe the reason the response rates
to PD-1 inhibitors are higher in classic Hodgkin
lymphoma than in any other type of cancer studied
to date.
The FDA approval of nivolumab for classic
Hodgkin lymphoma was based on an early clinical
trial in which lymphoma went into remission in 53
(66%) of 80 patients and disappeared entirely in
seven.28 Nearly all patients with classic Hodgkin
lymphoma who responded to the treatment had
at least a 50% reduction in the amount of cancer
in the body, and responses lasted 8 months, on
average. Nivolumab was generally well tolerated.
The most common adverse effects of any grade
were fatigue, infusion-related reaction, and skin rash.
Severe adverse effects, such as low blood counts
(neutropenia) and liver enzyme abnormalities
(increased lipase), occurred in only 5% of patients.
In another early trial, pembrolizumab was also
effective among young patients with relapsed or
treatment-resistant classic Hodgkin lymphoma.29
In 20 (64%) of 31 patients, the cancer went into
remission, and of those patients, five experienced
complete remission. Nearly all patients had some
reduction in tumor size, and most responses lasted
more than 24 weeks. In April 2016, the FDA granted
pembrolizumab breakthrough therapy designation
for treatment of relapsed classic Hodgkin
lymphoma.
Further research into PD-1 checkpoint
inhibitors as therapy for relapsed as well as
newly diagnosed classic Hodgkin lymphoma is
underway. Ongoing clinical trials are exploring
combinations of nivolumab with brentuximab
vedotin and ipilimumab (ClinicalTrials.gov identifiers:
NCT02758717, NCT01896999, and NCT02304458).
Pembrolizumab is also being tested in a range
of other hematologic malignancies, as well as
in multiple myeloma (ClinicalTrial.gov identifier:
NCT01953692).
EMERGING CLUES ON
PATIENT SELECTION
Despite the broadening landscape of
immunotherapy use, a difficult biology puzzle
remains to be solved. Why do immune checkpoint
inhibitors work so well in some cancers and not at
all in others? Among patients with the same type
of cancer, why do some respond to immunotherapy
while others do not?
The next chapter of immunotherapy research
will focus on answering these questions. Given
the high cost and considerable adverse effects
of immunotherapy approaches, it is all the more
important to be able to determine who is likely
to benefit the most. Although there can never be
complete certainty about whether a cancer will
respond to treatment, in most cases physicians can
at least estimate the likelihood of benefit, based on
the biologic characteristics or biomarkers of the
patient and the tumor.
Scientists are only beginning to unravel the
biomarkers that may predict a favorable response
to immunotherapy. For example, researchers
expected that cancers with high levels of PD-L1
would respond well to PD-1 checkpoint inhibitors
and that those without PD-L1 would not benefit at
all. However, in a number of different cancers, such
as ovarian cancer and melanoma, the relationship
between PD-L1 and response to PD-1 checkpoint
inhibitors has been less clear. In several clinical trials,
cancers with even low levels of PD-L1, including
some lung cancers, responded to PD-1 inhibitors.
A major issue is the lack of standardization of
PD-1 and PD-L1 analyses. It is unclear which assay
or reagent is optimal or whether expression in only
the cancer cells or in cancer cells plus surrounding
stromal and/or immune cells should be counted.
Furthermore, even using one assay and one method
of analysis, cutoffs have varied. These issues need
to be resolved before this marker can be considered
sufficiently robust for clinical decisions.
CLINICAL CANCER ADVANCES 2017
15
FDA BREAKTHROUGH
THERAPY DESIGNATION
AND PRIORITY REVIEW
The FDA breakthrough therapy designation
serves to expedite the development and review
of drugs for treating serious or life-threatening
illnesses where preliminary clinical data suggest
a drug may provide a substantial improvement in
patient outcomes. The designation helps ensure
patients gain faster access to promising new
treatments through FDA approval. A priority
review designation means the FDA aims to take
action on an application within 6 months.
Meanwhile, researchers are also exploring what
causes cancers that shrink in response to PD-1
checkpoint inhibitors to eventually start growing
again. A pilot study of patients with melanoma
suggested that mutations in certain immunerelated genes may be responsible for development
of resistance to PD-1 blockade (this study was
supported in part by a grant from the NIH).30
CHECKPOINT INHIBITORS WORK WELL
AGAINST HYPERMUTATED CANCERS
Although research on biomarkers for immune
checkpoint inhibitors and other types of
immunotherapy is still evolving, a few key clues
have emerged. For one, it seems that tumors with
a large number of mutations are more susceptible
to checkpoint inhibitors. The likely explanation for
this is that tumors with more mutations make more
abnormal proteins (antigens) that the immune
system recognizes as foreign.
Several tests have been proposed to evaluate
mutational burden. One involves sequencing the
entire genome of the cancer and simply counting
the number of mutations. Yet another approach is
to sequence only a selected panel of representative
genes and again determine the rate of mutations
within the panel. A third is to evaluate surrogate
markers of mutational frequency. Another assay
determines the presence of a hypermutatable
phenotype, such as apolipoprotein B mRNA
editing enzyme, catalytic polypeptide-like
(APOBEC) enzymes.
Cancers with a large number of mutations, socalled hypermutated cancers, are primarily those
16
CLINICAL CANCER ADVANCES 2017
caused by tobacco (eg, lung, head and neck,
and bladder cancers) or UV light exposure (eg,
melanoma and head and neck cancer). In fact,
tobacco and UV light exposure have been linked
to unique patterns of genetic changes or genetic
signatures.31 It is therefore not surprising that in
clinical trials to date, those are the cancers in
which immune checkpoint inhibition has been the
most effective.
Scientists have also reported that cancers
of patients who have a genetic abnormality
called mismatch repair (MMR) deficiency, which
undermines the ability of a cell to repair DNA
damage, also have many mutations. Early research
suggests that patients with MMR-deficient
colorectal or brain cancer benefit from checkpoint
inhibitors. These treatments, however, have low
efficacy in patients with the same cancers that are
not MMR deficient.
Taken in total, these exciting data are promising
but preliminary. It is hoped that ongoing studies will
help to determine if one or more tests can be used
to focus immune checkpoint inhibitor therapy on
those patients most likely to benefit.
Colorectal cancer. MMR
deficiency occurs in 15%
of colorectal cancers, but
it may also occur in other
gastrointestinal cancers,
as well as in endometrial,
prostate, and ovarian
cancers. A clinical trial
reported in 2015 points to a
relationship between MMR
image needed
deficiency and response to immune checkpoint
inhibitors (this study was funded in part by a grant
from the NIH).32
Among patients with MMRdeficient colorectal cancers, four of 10 responded
to the PD-1 checkpoint inhibitor pembrolizumab.
In contrast, none of the 18 patients without MMR
deficiency responded to pembrolizumab. Patients
with MMR deficiency had a mean of 1,782 mutations
per tumor, whereas those with normal MMR function
had only 73 mutations per tumor.
Although more research is needed, these early
findings suggest that testing for MMR deficiency
or the number of mutations in the tumor, so-called
mutational load, may help identify patients who
are likely to benefit from PD-1/PD-L1–directed
immunotherapy. Such tests are already available
in the clinic.
Childhood brain cancer. In
2016, researchers reported
that another MMR-deficient
cancer may be susceptible
to checkpoint inhibitors:
pediatric glioblastoma
multiforme (GBM).33 This
is a hard-to-treat cancer.
Most children with GBM will
experience a recurrence
of cancer despite surgery, radiation therapy, and
chemotherapy. With a median survival of 6 months,
children with recurrent GBM are in urgent need of
effective therapies.
The study focused on children with a rare
childhood cancer predisposition syndrome known
as biallelic MMR deficiency. All children with this
syndrome develop cancer in the first two decades of
life, most commonly brain, blood, or GI cancer.
The researchers analyzed the rates of genetic
mutations in 37 biallelic MMR-deficient tumors from
different tissues. Although all high-grade tumors
had large numbers of mutations (1,589 on average),
biallelic MMR-deficient GBMs had the highest by far
(17,740 mutations on average), and biallelic MMRdeficient GBMs had significantly more mutations
than all other pediatric or adult brain cancers.
Given previous research suggesting that tumors
with a large number of mutations respond well to
immune checkpoint inhibitors, researchers expected
to see good results in pediatric biallelic MMRdeficient GBM. In this pilot study, two siblings with
recurrent biallelic MMR-deficiency were treated
with nivolumab. After 12 weeks of therapy with
nivolumab, tumors shrank in both children, and their
health condition improved. After 9 and 5 months
of therapy, respectively, the sister and brother had
resumed schooling and daily activities.
According to the authors, this is the first report
of durable responses to immune checkpoint
inhibitors for recurrent GBM. These findings are
encouraging, because most children with recurrent
GBM experience disease worsening within only 1 or
2 months from time of recurrence and die within 3
to 6 months.
The findings may also have implications for
adult patients with GBM, as well as in other cancers
with MMR deficiency. More broadly, this research
underscores the possible utility of genetic testing
to select patients for immune checkpoint inhibitor
therapy.
CLINICAL CANCER ADVANCES 2017
17
Merkel cell carcinoma.
Another rare cancer that
seems to be susceptible to
PD-1 checkpoint inhibitors
is an aggressive skin
cancer called Merkel cell
carcinoma. Advanced
Merkel cell carcinoma
typically worsens within
3 months of initial treatment with chemotherapy.
As with other skin cancers, Merkel cell carcinoma
is caused by exposure to UV light. In addition,
approximately four of five occurrences of Merkel cell
carcinoma are linked to infection with the Merkel cell
polyomavirus (MCPyV).
PD-L1 is found in half of Merkel cell carcinomas,
and PD-1 is present on both the cancer-specific and
the MCPyV-specific immune cells. Furthermore, the
median number of mutations in MCPyV-negative
Merkel cell carcinoma (ie, 1,121) is greater than
that reported for other cancers that respond to
PD-1/PD-L1 checkpoint inhibitor therapy. This high
number of mutations, coupled with PD-1 and PD-L1
markers, suggests that Merkel cell carcinoma may
be well suited for treatment with a PD-1 checkpoint
inhibitor.
In a pilot study, tumors shrank in 14 (56%) of
26 patients with advanced Merkel cell carcinoma
on treatment with pembrolizumab (this study was
funded in part by a grant from the NCI).34
The treatment responses lasted from 2.2 to 9.7
18
CLINICAL CANCER ADVANCES 2017
months. In another clinical trial, 28 (32%) of 88
patients with chemotherapy-resistant Merkel cell
carcinoma experienced tumor shrinkage after
treatment with the PD-L1 inhibitor avelumab.35
Although longer follow-up and larger studies
are needed, these early findings suggest that
checkpoint inhibitors may slow the growth of Merkel
cell carcinoma.
Merkel cell carcinomas associated with MCPyV
have 100 times fewer mutations (median, 12
mutations) than MCPyV-negative cancers. In fact,
MCPyV-positive tumors have fewer mutations than
reported for cancers that respond poorly to PD-1
inhibitors, such as prostate and pancreatic cancers.
Despite this small number of mutations, MCPyVpositive tumors have higher response rates to
pembrolizumab (62%) than MCPyV-negative
tumors (44%).
Researchers postulate that MCPyV-positive
tumors may respond well to immunotherapy
because viral proteins (antigens) trigger an immune
response. This means that when PD-1 checkpoint
inhibitors unleash the immune system, it is already
primed to react against the cancer. This finding may
have implications for treatment of other cancers
linked to viruses.
XXFor additional notable advances in cancer
immunotherapy, please see Appendix Table A1.
u C
AN C ER RISK , PRE VENTIO N AN D SC REEN IN G
In 2016, a growing understanding of cancer biology has spurred
new insights into genetic mutations that predispose people to
different cancers. Knowing that a person carries a mutation in a cancer
susceptibility gene is important, because outcomes can be improved through
frequent cancer screening and preventive surgery. In addition, identifying
cancer susceptibility factors can help direct cancer treatment decisions and
inform family planning.
Every opportunity to prevent cancer is welcome news. Last year, researchers
reported on a new way to reduce the risk of nonmelanoma skin cancer: a
simple vitamin B pill. In addition, ASCO issued a policy statement outlining
recommendations to increase the uptake of human papilloma virus (HPV)
vaccination. These vaccines prevent cervical and other HPV-related cancers and
have the potential to save millions of lives. Meanwhile, researchers identified a
range of barriers that contribute to lower cervical and breast cancer screening
rates among Latina women.
CLINICAL CANCER ADVANCES 2017
19
ADDITIONAL GENES LINKED TO
OVARIAN CANCER RISK
A woman with a single first-degree relative (eg,
mother, daughter, or sister) with ovarian cancer has
a three-fold increased risk of developing ovarian
cancer; the risk goes up when two or more firstdegree relatives have been diagnosed with ovarian
cancer. More information on ovarian cancer and
familial risk can be found at Cancer.Net.
An estimated 10% to 15% of ovarian cancers
are linked to genetic mutations that are passed
down within a family. For example, the chance of
developing ovarian cancer is 36% for women with
mutations in the BRCA1 gene and 12% for those with
mutations in BRCA2. By comparison, in the general
population of women, the risk of developing ovarian
cancer over a lifetime is only 1% or 2%.36
A recent large study showed that mutations in
two other genes may make women susceptible to
ovarian cancer. Women with mutations in RAD51C
and RAD51D genes have a five- and twelve-fold
higher risk for ovarian cancer, respectively, than
women in the general population (this study was
funded in part by a grant from the NIH).37
In fact, researchers estimate that mutations in
RAD51 genes may be responsible for one in every
120 ovarian cancers.
Although these mutations are rare, knowing
that a woman has these risk factors is important,
A POLICY FOCUS:
GENETIC TESTING
Genetic counseling and testing has become a growing part of cancer risk
assessment, diagnosis, and treatment planning. Through policy statements, expert
guidelines, and quality programs, ASCO is helping oncology professionals integrate
genetic counseling and testing into clinical practice.
In the context of cancer, genetic testing can be used to confirm or rule out a
hereditary predisposition to cancer (approximately 5% to 10% of cancers are
hereditary) and to identify genetic changes in cancer cells that may respond to specific molecularly
targeted cancer treatments, helping a physician and patient identify the best treatment option.
During the past year, some insurance companies have adopted policies that hinder oncologists’ ability to
order genetic tests for their patients. ASCO opposes any policy that introduces an unnecessary barrier to
the appropriate use of genetic testing services or has the potential to negatively affect patient care.
20
CLINICAL CANCER ADVANCES 2017
VOICES OF CANCER RESEARCH
DAVID DESSERT
“I knew that I had a
BRCA2 mutation in
the family, but I had
not yet been tested.”
In 2010, a pancreatic cancer diagnosis confirmed it: David carried
a BRCA2 gene mutation that increased his risk of certain cancers.
The treatment David received at the time was successful, but the
risk of his cancer returning was high. A clinical trial, however, gave
him new hope. For the past three and a half years, David has been
receiving the GVAX vaccine, an immunotherapy designed to reduce
the risk of pancreatic cancer recurrence.
“Every treatment we have right now, we have because someone
else tried it in a clinical trial,” David said. “Hopefully this will help
somebody else down the line.”
David is a pancreatic cancer forum moderator at cancerforums.net, a member
of the peer navigator program at Facing Our Risk of Cancer Empowered (FORCE),
and a blogger for pancreatica.org.
because steps can be taken to lower ovarian cancer
risk. The findings from this study have led to a
change in the national guidelines on genetic testing.
The updated guidelines recommend consideration
of surgery (salpingo-oophorectmy) to reduce the
risk of ovarian cancer in women who have mutations
in RAD51C or RAD51D genes. For women with highrisk gene mutations, such as BRCA1 and BRCA2,
the genes related to Lynch syndrome, and others,
having the ovaries and fallopian tubes surgically
removed can reduce ovarian cancer risk by 70%
to 96%.
For women who are already diagnosed with
ovarian cancer, testing for RAD51 gene mutations
can also inform treatment decisions. Past research
has suggested that women who have such
mutations may respond well to a novel class of
drugs known as poly (ADP-ribose) polymerase
(PARP) inhibitors.
PANCREATIC CANCER SUSCEPTIBILITY
GENES IDENTIFIED, AND NEW
OPPORTUNITIES FOR SCREENING
AND PREVENTION
Approximately one in 10 pancreatic cancers is
associated with a gene mutation that is passed on
in a family from one generation to the next. When
pancreatic cancer occurs in two or more first-degree
relatives, it is referred to as familial pancreatic
cancer. Predisposition to pancreatic cancer has been
linked to mutations in a number of different genes,
including BRCA1 and BRCA2. In 2015, a prospective
study found BRCA mutations in 5% of patients
with the most common type of pancreatic cancer:
pancreatic ductal adenocarcinoma.38
However, the frequency of BRCA mutations
was higher (12%) among 33 patients of Ashkenazi
Jewish descent. (According to prior studies, BRCA
mutations are also more common among Ashkenazi
women with breast or ovarian cancer, compared
with the general population). Although the numbers
were small, this finding led to a change in national
genetic testing guidelines so that every Jewish
individual with pancreatic cancer is recommended
to undergo BRCA1/2 testing. Relatives of BRCA1/2
mutation carriers who are found to have the familial
mutation can be offered appropriate preventive
strategies, including screening to detect pancreatic
cancer at an early stage.
Given that the average person has only a 1%
chance of developing pancreatic cancer over a
lifetime, general screening for pancreatic cancer is
not recommended. However, selective screening of
people who are at high risk for pancreatic cancer
may detect premalignant tumors or early-stage
cancers, both of which are potentially curable
with surgery.
The benefit of such screening was evaluated
in a recent prospective screening study of 411
asymptomatic people with familial pancreatic
cancer or mutations in known pancreatic cancer
susceptibility genes (eg, CDKN2A, BRCA1/2,
and PALB2).39 Screening tools included annual
magnetic resonance imaging, magnetic resonance
cholangiopancreatography, and endoscopic
ultrasound. The median follow-up time was
32 months.
CLINICAL CANCER ADVANCES 2017
21
Pancreatic ductal adenocarcinoma was detected
in 13 (7%) of 178 CDKN2A mutation carriers, nine of
whom underwent surgery. The 5-year survival rate
was 24%, which is five-fold higher than the 5-year
survival rate for all patients diagnosed with this
cancer. In addition, screening detected pancreatic
cancer in only two (0.9%) of 214 individuals with
familial pancreatic cancer and one (5%) of 19
patients with BRCA mutations.
This study is the first to our knowledge to
demonstrate success in detecting early cancers and
favorable outcomes with surgery using pancreatic
cancer screening in a high-risk population. Although
screening was clearly useful in detecting pancreatic
cancer among patients with CDKN2A mutations,
more research is needed to assess the benefit of
screening in other high-risk groups, such as people
with familial pancreatic cancer or BRCA mutations.
BROADER TESTING UNCOVERS
UNEXPECTED CANCER
PREDISPOSITION GENE MUTATIONS
People with Lynch syndrome have a markedly
increased risk of developing colorectal, endometrial,
ovarian, gastric, pancreatic, urinary tract, and other
cancers, often at a young age. The syndrome is
caused by mutations in the following genes: MLH1,
MSH2, MSH6, PMS2, or EPCAM. Conventional Lynch
syndrome testing only screens for mutations in
these five genes. However, up to half of families
with suspected Lynch syndrome test negative for
such mutations, which suggests that other genetic
changes may be causing increased risk of cancer.
To address this question, researchers used a new
technology known as multigene panel testing, which
can rapidly analyze numerous cancer susceptibility
genes (this study was funded by a grant from the
NCI).40
They evaluated 25 cancer predisposition
genes among 1,260 people who were referred for
Lynch syndrome testing.
Although 114 (9%) participants had a mutation
22
CLINICAL CANCER ADVANCES 2017
in one of the Lynch syndrome genes, 71 (6%) had
mutations in other cancer predisposition genes.
For example, 15 people had mutations in BRCA1
or BRCA2 genes (linked to increased chance of
developing breast, ovarian, and other cancers), and
nine other individuals had a mutation in a colorectal
cancer susceptibility gene.
This study shows that multigene panel testing
may yield clinically useful information that could
be missed by the more limited, traditional Lynch
syndrome testing. It could reveal genetic changes
that would not be suspected based on family history
alone, allowing for preventive measures such as
screening and surgery.
One downside of broad-based genetic
testing, however, is the possibility of discovering
genetic mutations that have an uncertain clinical
significance. Such findings can cause considerable
anxiety in patients. In this study, 38% of the people
tested had one or more such uninformative findings.
MANY CHILDREN WITH CANCER MAY
CARRY HEREDITARY GENE MUTATIONS
The reasons a child develops cancer are
often poorly understood. It is largely unknown
how common hereditary mutations in cancer
predisposition genes arise in children with cancer.
A better understanding of the genetic basis for
childhood cancer susceptibility would inform
treatment choices as well as genetic counseling for
patients’ families.
To address this gap in knowledge, researchers
conducted a large-scale genomic study of children
diagnosed with cancer before the age of 20 years
(this study was funded in part by a grant from
the NCI).41
The analysis focused on 565 genes,
including 60 that have previously been associated
with cancer predisposition syndromes.
They detected mutations in genes thought to
be linked to increased cancer risk in 8.5% of 1,120
children with cancer, a rate that was much higher
than that observed in a control group of 1,000
people without cancer (1.1%). Interestingly, the
majority (60%) of children with a hereditary cancer
predisposition mutation did not have a family
history of cancer.
These findings argue for greater screening for
hereditary genetic predisposition in children with
cancer, even in the absence of a family history of
cancer. For the patient, identification of hereditary
mutations may influence treatment selection and
guide family planning. For the patient’s relatives,
having this information can prompt them to request
their own genetic testing and/or consider cancer
prevention measures.
DAILY VITAMIN B REDUCES SKIN
CANCER RISK
Excessive sun exposure is a widely recognized
risk factor for skin cancer. Despite sun protection
campaigns, the rates of skin cancer continue to rise
worldwide. Nonmelanoma skin cancer is the most
common type of cancer in fair-skinned populations
worldwide. More than one in two Australians
will develop a nonmelanoma skin cancer in their
lifetime.42 In the United States, 5 million people
are treated for skin cancer every year.43 Although
nonmelanoma skin cancer is rarely fatal, its
treatment poses a significant burden on health
care systems.
A POLICY FOCUS:
ASCO CALLS FOR INCREASED USE OF
HPV VACCINATION TO PREVENT CERVICAL CANCER
In April 2016, ASCO released a policy statement calling on its member
oncologists to help lead the push for all adolescents and young adults to be
vaccinated against cervical and other cancers. Published in the Journal of
Clinical Oncology, the statement outlines current barriers to the use of human
papillomavirus (HPV) vaccination, and recommendations to promote the
uptake of these vaccines, which have the potential to save millions of lives.
ASCO supports the recommendation to markedly increase the proportion
of young boys and girls receiving the HPV vaccine in the United States and
worldwide because research has shown that it is effective in preventing cancer.
Ongoing research confirms the public health benefit of HPV vaccines for
preventing cervical cancer.1
To this end, ASCO believes oncologists can play a vital role in increasing the
uptake of HPV vaccines. Although most oncologists are not the direct health
care providers for these preventive measures, they play an important role
through research and advocacy. ASCO encourages oncologists to advocate for
and actively promote policy changes to increase the use of HPV vaccination.
Bernard VB, Castle PE, Jenison SA, et al: Population-based incidence rates of cervical intraepithelial
neoplasia in the human papillomavirus vaccine era. JAMA Oncol [epub ahead of print on September 29,
2016]
1
CLINICAL CANCER ADVANCES 2017
23
Over the past decades, researchers have explored
a broad range of vitamins and supplements for
cancer prevention. However, only a few substances
with properties protective against cancer have been
identified to date. Recent research identified a form
of vitamin B3 called nicotinamide that can lower the
chance of developing skin cancer in people who are
at high risk for the disease.
In a clinical trial of people with a history of
nonmelanoma skin cancers, the rate of new skin
cancer diagnoses was 23% lower among people
who took the vitamin twice a day for a year.44 This
is the first clear evidence that skin cancers can be
prevented using a simple, inexpensive vitamin, along
with sun protection. Nonetheless, people at high
risk for skin cancer should continue to have regular
check-ups with their physicians.
This clinical trial builds on a decade of preclinical
and early clinical studies suggesting that
nicotinamide not only helps skin cells repair DNA
damaged by UV radiation but also protects the
skin’s immune system against UV light. The skin’s
immune system helps eradicate abnormal cells
before they become cancerous.
NEW UNDERSTANDING OF
BARRIERS TO CANCER SCREENING
AMONG LATINAS
In the United States, Latina women have the
lowest rates of compliance with cervical and breast
cancer screening recommendations. Women who
have long gaps between screenings or do not
receive any screening face a lower chance
of successful treatment and consequently
shorter survival.
24
CLINICAL CANCER ADVANCES 2017
Although prior research has explored extrinsic
sources of disparity in screening adherence, such as
limited access to care and lack of health insurance,
relatively little is known about intrinsic factors, such
as perceptions and attitudes. A survey of 87 Latina
women from New York and Arkansas who were
enrolled in a culturally tailored education program
to increase breast and cervical cancer screening
adherence has provided a wealth of information on
a variety of factors.45
Despite completing the education program, the
women were noncompliant with at least one of
the recommended screening examinations (clinical
breast examination or mammogram for breast
cancer; Pap test for cervical cancer). The most
commonly reported reasons for noncompliance
were logistic and organizational barriers (eg,
being out of the country for long periods of time,
forgetting to schedule an appointment), lack of time
(eg, inability to take time off from work), and lack
of interest in having a screening test. In addition,
several women were confused about when they
were due for an examination, and others believed
they did not need an examination as often as
guidelines recommend.
These new insights into factors that contribute
to perceptions of cancer screening may enable
development of tailored programs to improve
screening rates. Similar methodology can be used
to direct interventional programs related to other
aspects of cancer care.
XXFor additional notable advances in cancer
prevention and screening, please see
Appendix Table A1.
u A
DVAN C ES IN C AN C ER
TRE ATM ENT B E YO N D
IM M U N OTH ER APY
The past year has brought advances in the treatment of a broad
range of cancers. From November 2015 through October 2016, the FDA
approved eight new cancer treatments and 12 new uses of previously approved
cancer therapies (Table 1). The new approvals include immunotherapies for
bladder cancer and multiple myeloma and targeted treatments for hard-to-treat
forms of lung and kidney cancers, chronic lymphocytic leukemia (CLL), and
multiple myeloma. New-use approvals have broadened treatment options for
patients with melanoma, sarcoma, CLL, lymphoma, neuroendocrine tumors, and
breast, lung, kidney, and head and neck cancers. In addition, the FDA approved
the first liquid biopsy test in 2016.
Each year, 14 million people around the world learn that they have cancer.
Because cancer is mostly a disease of aging, cancer occurrences are expected
to increase as human lifespans are extended. Although prevention is the
ultimate goal, many factors that contribute to cancer cannot be controlled.
Advances in cancer treatment will therefore remain a key part of reducing the
global burden of cancer.
CLINICAL CANCER ADVANCES 2017
25
Table 1. FDA Approvals of Anticancer Therapies November 1, 2015 – October 31, 2016
Name of Drug
Indications
Date
NEW APPROVALS
Osimertinib
(Tagrisso)
Metastatic EGFR T790M mutation–positive NSCLC, as detected by FDAapproved test, progressing during or after EGFR TKI therapy
November 2015
Daratumumab
(Darzalex)
Multiple myeloma after three or more prior lines of therapy, including PI
and immunomodulatory agent, or disease double refractory to PI and
immunomodulatory agent
November 2015
Ixazomib
(Ninlaro)
In combination with lenalidomide and dexamethasone for multiple myeloma
after one or more prior therapy
November 2015
Necitumumab
(Portrazza)
In combination with gemcitabine and cisplatin for first-line treatment of metastatic
squamous NSCLC
November 2015
Alectinib
(Alecensa capsules)
ALK-positive metastatic NSCLC progressing with or intolerant to crizotinib
December 2015
Venetoclax
(Venclexta tablets)
CLL with 17p deletion, as detected by FDA-approved test, after one or more
prior therapy
April 2016
Cabozantinib
(Cabometyx)
Advanced RCC after prior antiangiogenic therapy
April 2016
Atezolizumab
(Tecentriq)
Locally advanced or metastatic urothelial carcinoma progressing during or
after platinum-containing chemotherapy or within 12 months of neoadjuvant or
adjuvant treatment with platinum-containing chemotherapy
May 2016
NEW USES
Trametinib (Mekinist)
and dabrafenib
(Tafinlar)
In combination for unresectable or metastatic melanoma with BRAF V600E or
V600K mutation as detected by FDA-approved test
November 2015
Nivolumab
(Opdivo)
Advanced RCC after prior antiangiogenic therapy
November 2015
Ofatumumab
(Arzerra injection)
Extended treatment for patients in complete or partial response after two or
more lines of therapy for recurrent or progressive CLL
January 2016
Eribulin
(Halaven injection)
Unresectable or metastatic liposarcoma after prior anthracycline-containing
regimen
January 2016
Palbociclib
(Ibrance capsules)
In combination with fulvestrant for hormone receptor–positive, HER2-negative
advanced or metastatic breast cancer progressing after endocrine therapy
February 2016
Obinutuzumab
(Gazyva injection)
In combination with bendamustine followed by obinutuzumab monotherapy for
treatment of FL relapsing after or refractory to rituximab-containing regimen
February 2016
Everolimus
(Afinitor)
Progressive, well-differentiated, nonfunctional NET of gastrointestinal or lung
origin (unresectable, locally advanced, or metastatic disease)
February 2016
Crizotinib
(Xalkori)
Metastatic NSCLC with ROS1-positive tumors
March 2016
Lenvatinib
(Lenvima)
In combination with everolimus for advanced RCC after one prior antiangiogenic
therapy
May 2016
Nivolumab
(Opdivo)
Classic HL relapsing or progressing after autologous HSCT and posttransplantation brentuximab vedotin (Adcetris)
May 2016
Liquid biopsy test
(cobas)
Detection of exon 19 deletions or exon 21 (L858R) substitution mutations in
EGFR gene to identify patients with metastatic NSCLC eligible for treatment
with erlotinib (Tarceva)
June 2016
Pembrolizumab
(Keytruda)
Recurrent or metastatic HNSCC progressing during or after platinum-containing
chemotherapy
August 2016
Atezolizumab
(Tecentriq)
Metastatic NSCLC progressing during or after platinum-containing
chemotherapy
October 2016
Abbreviations: ALK, anaplastic lymphoma kinase; CLL, chronic lymphocytic lymphoma; EGFR, epidermal growth factor receptor; FDA, US Food and
Drug Administration; FL, follicular lymphoma; HER2, human epidermal growth factor receptor 2; HL, Hodgkin lymphoma; HNSCC, head and neck
squamous cell carcinoma; HSCT, hematopoietic stem-cell transplantation; NET, neuroendocrine tumor; NSCLC, non–small-cell lung cancer;
PI, proteasome inhibitor; RCC, renal cell carcinoma; TKI, tyrosine kinase inhibitor.
26
CLINICAL CANCER ADVANCES 2017
TARGETED THERAPY
this is the largest clinical trial of patients with FLT3positive AML to date to our knowledge.
In addition to the growing success seen with
immunotherapy, 2016 was marked by a wave of
advances in precision medicine–based approaches.
They include treatments directed at novel molecular
targets, new types of treatment, and new ways to
combine traditional cancer treatments.
After 20 years, a promising new treatment of acute
myeloid leukemia. Acute myeloid leukemia (AML)
is the second most common type of leukemia
diagnosed in both adults and children. In 2016, an
estimated 19,950 people of all ages in the United
States were diagnosed with AML. This type of cancer
is difficult to treat, and only 27% of patients survive 5
years after diagnosis.46 More information on AML can
be found on Cancer.Net.
There have been no effective new treatments for
AML since the 1990s. In 2015, researchers reported
preliminary findings, which may lead to a new
standard of care for approximately one-third of
patients with AML, those with mutations in a gene
called FLT3 (this study was funded in part by a
grant from the NCI).47
Patients with FMS-related
tyrosine kinase 3 (FLT3)–positive AML have a poor
prognosis and a high chance of relapse.
In a large clinical trial, previously untreated
patients who received a therapy targeting FLT3
called midostaurin, combined with standard
chemotherapy, lived years longer than those who
received chemotherapy alone. The median survival
was 75 months among patients who received
midostaurin with chemotherapy and only 26
months among those who received placebo with
chemotherapy. Midostaurin also more than doubled
the median event-free survival (defined as death,
relapse, or no complete remission within 61 days)
achieved with chemotherapy alone (8 v 3.6 months).
The overall rates of severe adverse effects and
treatment-related deaths were similar between the
midostaurin and placebo groups. With 717 patients,
PATIENTS WHO RECEIVED A
THERAPY TARGETING FLT3,
called midostaurin, with standard
chemotherapy, lived years longer than
those who received chemotherapy alone.
75
MONTHS
26
MONTHS
New treatment targeting common marker improves
outcomes after acute lymphoblastic leukemia relapse.
In 2016, an estimated 2,636 adults in the United
States were diagnosed with acute lymphoblastic
leukemia (ALL).48 Although a majority of adults with
ALL achieve complete remission after initial therapy,
many eventually relapse. The prognosis for such
patients is poor, and more effective treatments are
urgently needed.
One new treatment, inotuzumab ozogamicin,
may improve outcomes for older people with
recurrent ALL, according to an ongoing clinical
trial.49 Inotuzumab ozogamicin belongs to a new
class of cancer treatments known as antibody–drug
conjugates (ADCs). These comprise an antibody
chemically linked to a powerful cancer drug called
calicheamicin. The antibody targets the CD22
molecule, found on tumor cells in 90% of patients
with B-cell ALL, and helps deliver calicheamicin to
leukemia cells.
In this late-stage trial, patients were randomly
assigned to receive inotuzumab ozogamicin or
standard intensive chemotherapy. The rate of
complete remission was more than two-fold higher
in the inotuzumab ozogamicin group compared
with the standard therapy group (81% v 29%). The
median time until cancer worsened was longer in the
inotuzumab ozogamicin group than in the standard
therapy group (5 v 1.8 months), and the median
survival was longer as well (7.7 v 6.7 months).
A major adverse effect of inotuzumab ozogamicin
was veno-occlusive liver disease, which occurred
in 11% of patients. Inotuzumab ozogamicin is likely
to become a new standard of care for older adult
patients with relapsed or refractory B-cell ALL.
Progress in treating advanced, ALK-positive NSCLC.
Approximately 3% to 7% of NSCLCs are anaplastic
lymphoma kinase (ALK) positive, meaning that the
cancers carry a genetic change known as ALK gene
rearrangement. The first treatment to specifically
target ALK-positive tumors, crizotinib, was approved
by the FDA in 2011. Although crizotinib shrinks tumors
in a large proportion of patients, most experience a
relapse within the first year of treatment.
To address the challenge of crizotinib resistance,
researchers have been developing more potent,
next-generation ALK inhibitors. One such treatment,
alectinib, has shown encouraging results in patients
with crizotinib-resistant, advanced NSCLC, including
those with brain metastases.50 In an early-stage
clinical trial, 48% of patients responded to alectinib,
with a median duration of response of 13.5 months.
Notably, in 75% of patients with NSCLC and brain
metastases, brain lesions shrank with alectinib.
This is a promising finding, because chemotherapy
CLINICAL CANCER ADVANCES 2017
27
has had limited efficacy in the central nervous
system (CNS), with response rates of only 45%. In
late 2015, the FDA approved alectinib for people
with ALK-positive NSCLC who cannot tolerate
crizotinib or whose cancer worsens after crizotinib.51
Overall, alectinib was well tolerated, with the most
frequently reported adverse effects being nausea
and diarrhea. Severe liver enzyme abnormalities
occurred in 6% of patients.
Preliminary findings from an ongoing late-stage
clinical trial suggest that alectinib may also help
previously untreated patients with advanced, ALKpositive NSCLC.52 In this study, tumors shrank in 92%
of patients treated with alectinib compared with
79% of those treated with crizotinib. Patients who
received alectinib had a 66% lower risk of disease
worsening than those treated with crizotinib.
Moreover, alectinib was better tolerated than
crizotinib, causing fewer adverse effects. Only one
adverse effect, constipation, occurred in more than
30% of patients in the alectinib group. In contrast,
several adverse effects, including nausea, diarrhea,
vomiting, and visual disturbance, occurred in
more than half of patients treated with crizotinib.
Another worldwide phase III trial of this same
treatment comparison (ClinicalTrials.gov identifier:
NCT02075840) is underway.
New regimen halts multiple myeloma progression.
Multiple myeloma is a cancer of plasma cells, which
are found in the bone marrow and make antibodies
to fight infections. Abnormal plasma cells can crowd
out or suppress the growth of other cells in the bone
marrow, resulting in anemia, excessive bleeding, and
decreased ability to fight infections.
In 2016, an estimated 30,300 people in the United
States were diagnosed with multiple myeloma.53
Multiple myeloma often recurs despite treatment.
Fewer than half of people with multiple myeloma
will live 5 or more years after diagnosis.
Early findings from a late-stage trial suggest
that a three-drug combination may improve
outcomes for patients with recurrent or treatmentresistant multiple myeloma.54 The new regimen
adds the novel therapy daratumumab to a standard
combination of bortezomib and dexamethasone.
Treatment that incorporated daratumumab
resulted in a 70% lower risk of cancer progression
than the standard two-drug regimen. In addition,
partial response rates were increased from 29% to
59% with daratumumab, and complete response
rates from 9% to 19%. Treatment-related adverse
effects were generally similar between the two
groups. However, low platelet counts, peripheral
neuropathy, diarrhea, and anemia occurred more
frequently with the daratumumab regimen.
Daratumumab targets a molecule on plasma cells
called CD38. It is one of the first cancer treatments
with a two-pronged mode of action: it has the
28
CLINICAL CANCER ADVANCES 2017
ability to destroy cancer cells directly and coax
the immune system to attack the cancer. On the
basis of results of an earlier clinical trial, the FDA
granted daratumumab accelerated approval for the
treatment of multiple myeloma in 2015.
Longer patient follow-up is required to
determine if the addition of daratumumab helps
patients live longer. Meanwhile, a clinical trial of
daratumumab combined with a different standard
regimen for patients with recurrent multiple
myeloma is underway (ClinicalTrials.gov identifier:
NCT01615029). Additional clinical trials testing
various daratumumab-based regimens in patients
with previously untreated multiple myeloma are
also in progress (ClinicalTrials.gov identifiers:
NCT02252172 and NCT02195479).
New class of targeted treatments for advanced breast
cancer. Hormone receptor–positive breast cancer is
the most common type of breast cancer. Although
hormone (antiestrogen) therapy is the standard of
care for patients with hormone receptor–positive,
human epidermal growth factor receptor 2 (HER2)–
negative metastatic breast cancer, its clinical benefit
is modest, and treatment resistance remains a
significant challenge.
In 2016, researchers reported updated results
from a large clinical trial of a new targeted
treatment of metastatic breast cancer: palbociclib.55
Palbociclib is a pill that works by blocking two
molecules involved in breast cancer resistance
to hormone therapy: cyclin-dependent kinase 4
(CDK4) and cyclin-dependent kinase 6 (CDK6).
CDK4/6 inhibitors are a new class of targeted
treatments that may have a role in many different
types of cancer in the future.
The study enrolled women with hormone
receptor–positive, HER2-negative metastatic breast
cancer that had worsened with prior hormone
therapy. Women were randomly assigned to
treatment with palbociclib plus a standard hormone
therapy (ie, fulvestrant) or placebo plus fulvestrant.
In the trial, the addition of palbociclib to hormone
therapy nearly doubled the median time until
the cancer worsened to 9.5 months, compared
with 4.6 months with fulvestrant plus placebo.
Approximately two-thirds of women experienced
clinical benefit from the palbociclib regimen, and
one-quarter experienced tumor shrinkage. The
benefit of palbociclib was seen regardless of degree
of hormone therapy resistance, hormone receptor
level, and PIK3CA mutational status. However, the
rates of severe adverse effects were substantially
higher in the palbociclib group (73% v 22%). The
most common adverse effects were low blood
counts (neutropenia, anemia, and leucopenia).
Palbociclib has also been studied as initial
treatment for advanced breast cancer in
combination with hormone therapy. In a large
VOICES OF CANCER RESEARCH
RONA GREENBERG
“More time with
my daughters that’s my priority.”
Rona, a breast cancer survivor, had known that having a mutation in
the BRCA2 gene increased her risk of other cancers. Still, it came as a
shock when she was diagnosed with pancreatic cancer in 2015.
Since then, research advances have helped Rona survive. A targeted
therapy called veliparib in combination with chemotherapy shrank the
tumors for 10 months. While the treatment eventually stopped working,
the potential of precision medicine leaves Rona and her doctor
hopeful. She is now on another treatment that holds great promise.
Rona, pictured with her daughters, is a volunteer advocate with Facing
Our Risk of Cancer Empowered (FORCE) and Letswinpc.org.
clinical trial, postmenopausal women with estrogen
receptor (ER)–positive, HER2-negative breast cancer
were treated with either letrozole plus placebo or
letrozole plus palbociclib. Palbociclib extended the
median time until the cancer worsened from 14 to 25
months in this study.56 The adverse effects among
patients treated with palbociclib plus letrozole were
similar to those seen previously with palbociclib in
combination with fulvestrant (ie, low blood counts,
fatigue, and nausea).
In another clinical trial of first-line therapy for
ER-positive, advanced breast cancer, patients
were randomly assigned to receive letrozole plus
placebo or letrozole plus ribociclib, a CDK4/6
inhibitor.57 In this trial, ribociclib markedly slowed
cancer progression. After 18 months, cancer had not
worsened in 63% of patients in the ribociclib group,
compared with 42% of patients in the placebo
group. The clinical outcomes and adverse effects for
ribociclib and palbociclib seemed nearly identical.
It is not yet clear if palbociclib or ribociclib will
extend overall survival because follow-up has not
been sufficiently long nor have any biomarker tests
been shown to predict who will or will not benefit
from addition of these drugs. However, these findings
have already changed the standard of care for
patients with hormone receptor–positive metastatic
breast cancer. The FDA approved palbociclib plus
fulvestrant for women with disease progression after
hormone therapy in February 2016.58 Palbociclib
was previously approved for use with letrozole as
initial hormone therapy for patients with ER-positive,
HER2-negative advanced breast cancer.
More effective treatments for advanced kidney cancer.
An estimated 62,700 adults were diagnosed with
kidney cancer in the United States in 2016.59 Renal
cell carcinoma (RCC) is the most common type of
kidney cancer in adults. At the time of diagnosis,
nearly one-third of patients with RCC have metastatic
cancer. The 5-year survival for people with metastatic
RCC is only 12%. More information on kidney cancer
can be found on Cancer.Net.
Advances in understanding kidney cancer biology
led to the development of treatments targeting two
molecular pathways: vascular endothelial growth
factor receptor (VEGFR) and mammalian target
of rapamycin (mTOR). Introduced approximately a
decade ago, the treatments extend median survival
for patients with advanced kidney cancer from 1 to
3 years. The current standard-of-care treatment for
patients with recurrent, advanced kidney cancer
includes VEGFR inhibitors axitinib and sorafenib and
mTOR inhibitor everolimus.
In 2016, researchers reported findings from a
large clinical trial suggesting an even more effective
targeted treatment for relapsed RCC.60 Cabozantinib
is an oral treatment that blocks several different
targets in cancer cells, including tyrosine kinases
MET, VEGFR2, and AXL. The median overall survival
was 16.5 months in the group of patients treated
with standard-of-care everolimus and 21.4 months
in the group treated with cabozantinib. Patients
who received cabozantinib had a 49% lower risk of
cancer progression and substantially higher tumor
shrinkage rates (17% v 3%).
Severe-grade adverse effects that occurred more
frequently with cabozantinib than with everolimus
included high blood pressure, diarrhea, and fatigue.
Anemia was more common in the everolimus group.
On the basis of the findings from this study, the FDA
approved cabozantinib in 2016 for the treatment of
advanced RCC in patients who had received prior
VEGFR inhibitor therapy.61
Two other large clinical trials explored VEGFR
inhibitors in patients with advanced, nonmetastatic
RCC who are at high risk of recurrence after surgery.
Up to 40% of patients with stage III RCC experience
a relapse with metastasis after kidney cancer
surgery.62 There is currently no standard treatment
for such patients, and the standard of care after
surgery is surveillance.
CLINICAL CANCER ADVANCES 2017
29
A POLICY FOCUS:
EFFORTS CONTINUE TO EXPAND ACCESS TO CLINICAL TRIALS
ASCO continues to be concerned that only 3% of adult patients with cancer
participate in clinical trials.1 This low participation rate not only limits patient
access to new interventions that could treat, or even cure, their cancer, but also
limits the knowledge gained from scientific inquiry to a small subset of patients.
ASCO submitted comments to the US Department of Health and Human
Services and the National Institutes of Health on proposed rules aimed
at increasing clinical trial participation and making clinical trial data more
accessible and useful. The final rule, released in September 2016, requires
researchers to register trials so that patients and their health care providers
can more easily access trial information and determine if a patient is eligible
to participate. In addition, researchers must also provide more detailed
trial summary results, including information on adverse health events, on
ClinicalTrials.gov.
Although this is a major step forward, more work is needed to expand access to
clinical trials. Patients with low socioeconomic status, older adults, and ethnic
and racial minority groups are under-represented in clinical trials. This impedes
our ability to make progress against cancer in the populations who experience
disparities in access to cancer care and treatment outcomes. ASCO continues
to work with policymakers to expand access to clinical trials by relaxing
overly restrictive eligibility requirements and by requiring Medicaid to cover
routine costs of care for clinical trial participants. ASCO also worked with the
American Association of Cancer Institutes through the Best Practices in Cancer
Clinical Trials Initiative to develop and promote practical solutions to meet
administrative and regulatory requirements in clinical cancer research.
Institute of Medicine Forum on Drug Discovery, Development, and Translation: Transforming Clinical
Research in the United States: Challenges and Opportunities: Workshop Summary. Washington, DC,
National Academies Press, 2010
1
In the S-TRAC (Sunitinib Treatment of Renal
Adjuvant Cancer) trial, patients with stage III clear
cell RCC were randomly assigned to treatment
with sunitinib or placebo after surgery to remove
the tumor.63 Sunitinib blocks VEGFR and several
other molecular targets. The period until the cancer
worsened was significantly longer in the sunitinib
group (median, 6.8 years) than in the placebo group
(median, 5.6 years). The rate of severe adverse
effects, such as skin rash, high blood pressure, and
fatigue, was higher in the sunitinib group than in the
placebo group (63% v 22%). Although these findings
are encouraging, longer follow-up is needed to
determine whether treatment with sunitinib in this
setting prolongs survival.
In contrast, a much larger clinical trial, ASSURE
(Adjuvant Sorafenib or Sunitinib for Unfavorable
Renal Carcinoma; ECOG-ACRIN E2805), found no
significant difference in the duration of disease-free
survival between patients who received placebo
(median, 6.6 years), sunitinib (median, 5.8 years), or
sorafenib (median, 6.1 years) after surgery
(this study was funded in part by a grant from
the NCI).64
The most common severe adverse
effects in the sunitinib and sorafenib groups were
30
CLINICAL CANCER ADVANCES 2017
high blood pressure, hand-foot reaction, rash, and
fatigue. Five deaths related to treatment occurred:
one in the sorafenib group and four in the sunitinib
group. The study authors concluded that neither
sunitinib nor sorafenib should be used as adjuvant
treatment for high-risk, advanced RCC.
Adjuvant VEGFR inhibitors should not be
administered in the clinic until additional data are
available to reconcile the differing results from the
S-TRAC and ASSURE trials. A more compelling
signal would be a trend toward survival benefit in
either study, which currently does not exist. With
multiple other adjuvant VEGFR studies underway,
more data should be available to adjudicate the
role of this treatment strategy. Physicians should
continue to encourage enrollment of patients in
ongoing trials that further explore the question.
Promising treatment for ovarian cancer. With survival
in the range of 12 to 18 months, women with
recurrent ovarian cancer are in desperate need of
better therapies. Research findings reported in 2016
may lead to a new approach to treat this difficult
cancer.65 In an early-stage clinical trial, four of 10
women with folate receptor alpha–positive ovarian
cancer resistant to standard platinum chemotherapy
experienced tumor shrinkage after receiving
IMGN853 (mirvetuximab soravtansine). The most
common adverse effects were diarrhea, eye
problems, cough, fatigue, and decreased appetite.
IMGN853 belongs to the new class of cancer
therapies known as ADCs. It comprises an antibody
targeting folate receptor alpha (a marker found in
most ovarian cancers) and a potent anticancer drug
called DM4, which blocks cell division and growth.
Additional clinical trials of IMGN853 in women with
folate receptor alpha–positive ovarian cancer are
already underway (ClinicalTrials.gov identifiers:
NCT02631876 and NCT02606305).
COMBINED MODALITY THERAPY
It is common that patients with cancer receive
two or more treatments at a time, at least at
some point during the course of their illness. Such
common modality therapies can work better than
standalone treatments, but this improved efficacy
often comes with more adverse effects. As with
all new approaches, before any new combination
of treatments becomes part of routine care, its
benefits and safety need to be evaluated in a clinical
trial against a standard treatment regimen. Last
year, clinical trials delivered important advances
in combined modality therapies for brain cancer,
neuroblastoma, and colorectal cancer.
Adding chemotherapy to radiation therapy extends
glioma survival. In 2016, scientists reported long-
awaited results from a federally funded clinical
trial of patients with grade 2 glioma (this study
was funded by a grant from the NCI).66
Grade 2
gliomas are rare, accounting for only 5% to 10% of
all brain tumors, and often occur in younger people.
Although low-grade gliomas grow slower than
other types of brain cancer, they lead to worsening
neurologic symptoms and often premature death.
In the study, patients were randomly assigned
to receive radiation therapy alone or radiation
therapy followed by PCV (procarbazine, CCNU,
and vincristine) chemotherapy. The median survival
was substantially longer among patients treated
with chemotherapy and radiation therapy (13.3
years) than among those who received radiation
MEDIAN SURVIVAL
13.3
YEARS
u treated with radiation therapy
and chemotherapy
7.8
YEARS
u treated with only
radiation therapy
therapy alone (7.8 years). Addition of chemotherapy
also slowed the course of the disease; at 10 years,
the cancer worsened in only 21% of patients in
this group. In contrast, cancer worsened in 51% of
patients treated with radiation therapy alone. This
study led to a change in the standard of care for
high-risk, low-grade gliomas; PCV chemotherapy is
now added to radiation therapy.
More effective regimen for children with high-risk
neuroblastoma. Neuroblastoma is the second most
common solid tumor in children and the most
common cancer in infancy. It begins in nerve cells
outside of the brain. Approximately 700 children
are diagnosed with neuroblastoma each year in the
United States, most younger than age 6 years. Highrisk neuroblastoma requires intensive treatment,
which may include surgery, chemotherapy, radiation
therapy, and/or autologous stem cell transplant
(ASCT). Despite all these treatments, fewer than half
of children will survive 5 years after diagnosis of a
high-risk neuroblastoma.
A federally funded trial performed by the
Children’s Oncology Group found that adding a
second autologous stem cell transplant or ASCT to
standard therapy can improve patient outcomes
(this study was funded in part by a grant from the
NCI).67
At 3 years, cancer had not recurred in 61%
of patients who had undergone two transplantations,
compared with 48% of patients who had undergone
one.
The 3-year survival rate was slightly higher
in the double transplantation group than in the
single transplantation group (74% v 69%), but this
difference was not statistically significant. This
study was not designed to observe a difference
in overall survival between the two treatment
groups. However, given that most neuroblastoma
recurrences occur within 2 to 3 years of diagnosis,
patients who had not experienced a recurrence at 3
years had a better chance of long-term survival.
The rates of severe adverse effects, such as
infections and liver problems, were similar between
the two treatment groups, although fewer treatmentrelated deaths occurred with double transplantation.
Nonetheless, it is important to keep in mind that the
combination therapy for high-risk neuroblastoma
is one of the most aggressive cancer regimens
administered to children. Longer patient follow-up
is needed to determine if there are any long-term or
late-onset adverse effects of this therapy.
Colon tumor location: a factor to consider in treatment
decisions. An unexpected factor may help explain
why some patients with colorectal cancer do better
than others. According to an analysis of data from a
large clinical trial, patients with advanced colorectal
cancer live longer if the cancer begins on the left
side of the colon rather than on the right side
CLINICAL CANCER ADVANCES 2017
31
COLORECTAL TUMORS:
RIGHT OR LEFT?
The answer might influence a patient's survival and
treatment choices, according to a new study of
patients with advanced colorectal cancers.
Ascending
colon
Descending
colon
Sigmoid colon
Rectum
LEFT
(this study was funded in part by a grant from
THE LOCATION OF THE PRIMARY TUMOR MAY...
the NCI).68
In the trial, patients received a
• Impactof
survival
• Help doctors
select the
combination
FOLFOX (fluorouracil,
leucovorin,
most beneficial targeted
and oxaliplatin) or FOLFIRI (fluorouracil, leucovorin,
treatment regimen*
and irinotecan) chemotherapy with either of the two
3 YRS
STUDY
standard targetedAFTER
therapies
for advanced colorectal
ENROLLMENT
cancer: cetuximab or bevacizumab. In prior research,
the two treatments yielded similar survival. In this
1.5 YRS
analysis, the
median survival for patients with
AFTER STUDY
ENROLLMENT
left-sided tumors was 33 months, but it was only
19 months for those with right-sided tumors.
RIGHT analysis
LEFT of data from two other
A separate
clinical trials also found that patients with advanced
colorectal cancer that began on the left side of the
colon lived longer than those with cancers that
began on the right side.69 Among patients with leftsided tumors,
the combination of cetuximab and
*In patients with advanced colorectal tumors that have a normal form of the KRAS gene
AP et al.effective
“Impact of primary (1º)than
tumor location
on overall survival (OS)
FOLFIRISOURCE:
wasVenook,
more
bevacizumab
and
and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC):
Analysis of CALGB/SWOG 80405 (Alliance).” J Clin Oncol 34, 2016 (suppl; abstr 3504).
FOLFIRI, whereas patients with right-sided tumors
experienced limited benefit from either regimen.
For now, the compelling findings from these
studies suggest that clinicians should take into
account the location of the primary tumor when
making treatment decisions for patients with
advanced colorectal cancer. For patients with a
right-sided colorectal cancer, cetuximab may not
provide a benefit. However, for those patients
whose tumors originate in the left colon, either
a bevacizumab- or cetuximab-based regimen is
effective, with cetuximab seeming to produce the
best outcomes when combined with chemotherapy.
Finally, an analysis of pooled data from 66
clinical trials and more than 1.4 million patients
revealed that left-sided primary colon tumors were
associated with a better prognosis than right-sided
tumors, irrespective of cancer stage.70 Overall,
patients with left-sided tumors had a 20% lower risk
of death. This analysis suggests that the location
of primary tumor should be considered when
establishing prognosis and designing future clinical
trials in both early and advanced colorectal cancers.
32
Even in the era of precision medicine,
chemotherapy remains a key treatment modality for
many patients with cancer. Along with development
of new chemotherapies, researchers are exploring
new ways to use conventional chemotherapies.
The past year brought important advances in
chemotherapy for treatment of patients with
pancreatic cancer and leukemia.
Pancreatic cancer: two-drug regimen increases chance
of living longer. Pancreatic cancer is often difficult to
Cecum
RIGHT
CHEMOTHERAPY
CLINICAL CANCER ADVANCES 2017
diagnose. As a result, it is often not found until it has
spread from the pancreas to other parts of the body
and can no longer be removed with surgery. Overall,
only 29% of patients with pancreatic cancer will be
alive 1 year after diagnosis. As the fourth leading
cause of death resulting from cancer in the United
States, pancreatic cancer took an estimated 42,000
lives in 2016.71
Patients who are diagnosed early enough for
surgical removal of the tumor have a chance of
longer survival. For the past two decades, the
standard of care after pancreatic cancer surgery
has been gemcitabine chemotherapy, which is
administered to eliminate remaining cancer cells and
reduce the chance of relapse. However, the benefit
of gemcitabine is relatively modest, with only 20%
of patients surviving 5 years.
A recent clinical trial found that adding a second
chemotherapy drug, capecitabine, to gemcitabine
can help such patients live even longer.72 The
median survival was 28 months in the group of
patients treated with the two-drug regimen and
25.5 months in the group that received gemcitabine
alone. Despite a small difference in median survival,
addition of capecitabine increased the chance of
surviving 5 years from 16% to 29%.
These results have set a new standard of care for
use of gemcitabine plus capecitabine as adjuvant
(postsurgery) therapy after pancreatic cancer
surgery. Gemcitabine and capecitabine are both
FDA approved for use in several different cancers
and are available as generic medicines.
The combination regimen was well tolerated
overall, with no significant increase in adverse
effects compared with gemcitabine alone. The
safety of the gemcitabine–capecitabine combination
allows for the possibility of adding other treatments
to this regimen with the goal of further improving
patient benefit.
High-risk AML: new packaging of conventional drugs
extends survival. With current therapy, people
with AML live only approximately 6 months after
diagnosis. There has been little improvement in
AML survival in the last few decades, but last year
brought not only a promising new targeted therapy
(described under Targeted Therapy), but also an
improved chemotherapy regimen.73
The new medicine, called CPX-351, packs
cytarabine and daunorubicin into a liposome, which
helps the chemotherapy slip into leukemia cells.
CPX-351 was investigated in a late-stage clinical trial
of older patients newly diagnosed with secondary
AML. Secondary AML can develop as a result of
treatment of another cancer or environmental
exposure to radiation or certain chemicals.
In the study, patients who received CPX-351 lived
approximately 4 months longer (median survival,
10 months) than those who received standard
combination chemotherapy (median survival, 6
months) with the same drugs. At 2 years, 31% of
patients were alive in the CPX-351 group versus
12% of patients in the standard chemotherapy
group. There were no differences in adverse effects
between the two groups of patients.
These findings represent a long-awaited advance
in treatment of older adults with high-risk or
secondary AML. The FDA has granted CPX-351 a
breakthrough therapy designation for treatment of
patients with AML.
NEW CONCERNS ABOUT LAPAROSCOPIC
RECTAL CANCER SURGERY
In recent years, laparoscopic surgery has
emerged as an attractive alternative to the
traditional open surgery because of its shorter
recovery time and lower rate of complications. The
procedure is performed with the aid of a video
camera and instruments inserted through small
incisions in the abdomen.
Patients with early and locally advanced rectal
cancer can be cured with surgery, provided the
tumor tissue is completely removed. However, the
choice between open and laparoscopic surgery is
not easy to make for such patients. Experts have
raised concerns that laparoscopic surgery may
not remove tumor tissue as completely as open
surgery does. As a result, patients who undergo
laparoscopic surgery may have a greater chance
of cancer recurrence and consequently shorter
survival.
In one recent clinical trial, rates of surgical
success (ie, complete tumor removal) were found
to be substantially lower among patients with rectal
cancer who underwent laparoscopic surgery than
among those who underwent open surgery (82%
v 87%).74 Similar trends were seen in another large
trial, where successful surgery was achieved in 82%
of patients undergoing a laparoscopic procedure
and 89% of patients undergoing open surgery.75
These findings confirm concerns that laparoscopic
surgery may lead to more cancer recurrences and
shorter survival. Patients enrolled in these two trials
will continue to be observed to answer this question.
Meanwhile, routine use of laparoscopic surgery is not
recommended for patients with stage II or III rectal
cancer. In contrast, laparoscopic surgery is a wellaccepted procedure for patients with colon cancer.
LONGER HORMONE THERAPY
FURTHER REDUCES BREAST CANCER
RECURRENCE
Breast cancer can recur many years after a woman
completes treatment for early-stage, hormone
receptor–positive breast cancer. To lower the chance
of recurrence, many women receive hormone
therapy after surgery. In 2016, researchers reported
that extending a form of hormone therapy called
aromatase inhibitors from the standard 5 years to 10
years may further reduce the risk of recurrence.76
The study enrolled postmenopausal women with
early breast cancer who had completed 5 years of
aromatase inhibitor hormone therapy either as firstline treatment or after tamoxifen. The women were
randomly assigned to receive the aromatase inhibitor
letrozole for 5 additional years or placebo.
The chance of breast cancer recurrence or
development of a second cancer in the opposite
breast was 34% lower in the letrozole group than in
the placebo group. At 5 years of follow-up, 95% of
women in the letrozole group and 91% of women in
A POLICY FOCUS:
ROBUST FEDERAL FUNDING
NEEDED FOR CANCER
RESEARCH PROGRESS
ASCO continues to urge legislators to make a
robust national investment in medical research
through the National Institutes of Health (NIH)
and the National Cancer Institute.
For much of the past decade, federal funding
for biomedical research has been flat, and
in inflation-adjusted dollars, the NIH budget
was 20% lower in 2016 than it was a decade
before.1 This dramatic drop in funding limits
the ability of scientists to conduct important
research that advances the prevention,
diagnosis, and treatment of cancer for millions
of people.
Even under tight budgetary constraints,
Congress must provide consistent and
predictable funding increases to continue our
momentum to prevent cancer and improve
cancer treatment for patients.
National Institutes of Health: Appropriations.
https://www.nih.gov/about-nih/what-we-do/nih-almanac/
appropriations-section-2
1
CLINICAL CANCER ADVANCES 2017
33
the placebo group remained breast cancer free. The
rates of second breast cancers were lower in the
letrozole group (0.2% v 0.5%). Nonetheless, 5-year
survival rates were not significantly different between
the two groups (letrozole, 94% v placebo, 93%).
Adverse effects of hormone therapy can be
difficult to bear, particularly over a long period of
time. Although bone pain, fractures, and osteoporosis
occurred more frequently with letrozole than with
placebo, researchers found no significant differences
in either overall quality of life or menopause-specific
symptoms.
Furthermore, a separate analysis of more than
45,000 patients who were observed for 15 years
after receiving 5 years of hormone therapy provides
a more accurate estimate of the risk of breast cancer
recurrence according to initial tumor stage, grade,
and lymph node status.77 The findings will help inform
decisions about continuing hormone therapy beyond
5 years.
These findings are important to millions of
women around the world who receive a diagnosis of
hormone receptor–positive breast cancer each year.
They provide much-needed direction to physicians
and patients discussing whether to extend hormone
therapy beyond the previous standard of 5 years,
particularly in women who found the first 5 years of
treatment acceptable.
XXFor additional notable advances in cancer
treatment, please see Appendix Table A1.
34
CLINICAL CANCER ADVANCES 2017
RECENT CLINICAL
PRACTICE GUIDELINES
Clinical practice guidelines help distill
knowledge about a particular clinical issue and
provide recommendations to help clinicians
deliver the best treatment and care to every
patient. ASCO develops its clinical practice
guidelines through a rigorous, systematic
review of relevant medical literature and
clinical interpretation from a multidisciplinary
panel of experts and patient representatives.
In 2016, ASCO issued more than 17 new clinical
practice guidelines, updates, adaptations, and
endorsements (Appendix, Table A2).
uT
o view the ASCO guidelines by clinical
area, visit asco.org/practice-guidelines/
quality-guidelines/guidelines.
uADVAN C ES IN PATIENT C ARE
Along with other areas of medicine, the cancer community has
embraced the concept of patient-centered care. Patients today are
encouraged to take an active role in their care from the moment of diagnosis,
and the latest research highlights both challenges and solutions for ensuring
every patient receives quality cancer care.
First, 2016 marked important milestones in two key initiatives that hold great
promise for people with cancer: CancerLinQ, ASCO’s big-data initiative to
rapidly improve the quality of cancer care, and the TAPUR (Targeted Agent
and Profiling Utilization Registry) study, which is the first clinical trial conducted
by ASCO.
In addition, an advance has been made in preventing nausea and vomiting in
patients receiving chemotherapy. Researchers have identified a more powerful
medication combination that will help ease these challenging adverse effects
of treatment. Not only does this advance improve patients’ quality of life, it also
helps more people complete the full dose and course of chemotherapy.
CLINICAL CANCER ADVANCES 2017
35
A POLICY FOCUS:
IMPORTANCE OF DATA SHARING IN CANCER CARE
AND RESEARCH
ASCO continues to advance policies that improve the widespread interoperability of electronic health
records, which refers to the ability to identify, extract, and use health care data within and among systems.
Interoperability is essential for the complex treatment of cancer because multiple health care providers
using different information systems need a way to exchange detailed clinical information to coordinate care
effectively. Furthermore, interoperability will provide a critical foundation for big-data efforts, including
ASCO’s CancerLinQ initiative, which holds great promise in unlocking advances by distilling massive volumes
of clinical data from large groups of patients with cancer.
ASCO was a major supporter of the 21st Century Cures Act, and congratulated President Obama,
Vice President Biden, and Congress when the legislation was signed into law and funded in December
2016. The law includes provisions to advance interoperability, such as requiring the secure access, transfer,
exchange, and use of all electronically accessible health information for authorized purposes, and banning
information blocking, which is the practice of knowingly and unreasonably interfering with the exchange or
use of electronic health information.
Now that 21st Century Cures Act has been signed into law, ASCO will continue to serve as a resource to
policymakers to support implementation.
New tools and programs, such as a Web-based
tool for self-monitoring symptoms and patient
navigation and education programs for underserved
populations with lower health literacy, are being
developed to improve care and quality of life. Such
programs will become increasingly important in the
era of precision medicine.
Finally, a major study reported in 2016 provides
long-awaited answers about outcomes with three
standard approaches for early prostate cancer:
active surveillance, surgery, and radiation therapy.
The findings will inform physician and patient
discussions about treatment.
ASCO ADVANCES PATIENT CARE
THROUGH PRECISION MEDICINE
AND BIG DATA
In early 2016, CancerLinQ—ASCO’s big-data
initiative to rapidly improve the quality of care
for people with cancer—went live. The number
of participating oncology practices grew steadily
throughout the year, ranging from small private
practices to some of the leading cancer centers in
the nation. More than 70 vanguard practices in
40 states and the District of Columbia have signed
on to feed patient data into CancerLinQ and use
the system in their practices. The rapid-learning
system run by CancerLinQ, a wholly owned
nonprofit subsidiary of ASCO, is now drawing on
more than 1 million patient records from across
the United States.
In addition, CancerLinQ has agreements in
place with Cancer Informatics for Cancer Centers
36
CLINICAL CANCER ADVANCES 2017
(CI4CC) and SAP. The collaborative agreement
with CI4CC, which represents senior informatics
leaders and chief data scientists at NCI-designated
cancer centers and other major medical and
research institutions across the nation, will bring the
nation’s leading clinical, genomic, and biomedical
informaticists, academicians, and data scientists
together with the oncology community to help
improve cancer care through CancerLinQ. The
CancerLinQ platform was codeveloped with SAP
using the SAP Connected Health platform that
runs on SAP HANA, a flexible, in-memory data
management and application platform created
by SAP.
CancerLinQ is continuing to add new practices
and will soon enable the cancer community to
begin to gain critical insights from the growing data
resources of the system that will improve cancer
care and spark new research.
The ASCO TAPUR study (ClinicalTrials.gov
identifier: NCT02693535) was also launched in
2016, officially opening patient enrollment on March
14. TAPUR is designed to evaluate molecularly
targeted cancer drugs and collect data on clinical
outcomes to learn about additional uses of these
drugs outside of indications already approved by
the FDA. It will offer flexibility, allowing physicians
to choose the tumor specimen or blood sample and
genomic profiling test; use broad general eligibility
criteria; and streamline data collection and reduce
the overall amount of data collected.
The precision medicine trial has enjoyed robust
expansion in just its first year, continuously
adding both patients and participating sites. As of
January 2017, seven pharmaceutical companies are
participating in TAPUR, providing 17 drugs that yield
15 different targeted therapy options (some of the
drugs are used in combination with one another) for
participants with advanced solid tumors, multiple
myeloma, or B-cell non-Hodgkin lymphoma;
additional drugs and companies may be added as
the trial continues.
This year, TAPUR is expected to expand
enrollment to include pediatric patients by
lowering the eligibility age from 18 to 12 years. This
will extend the opportunity for participation to
adolescent patients with advanced cancer.
BETTER WAY TO PREVENT
CHEMOTHERAPY-TRIGGERED NAUSEA
Nausea and vomiting are among the most
common adverse effects of chemotherapy.
These symptoms are not only uncomfortable and
debilitating, but may also be so severe that they
prevent patients from completing the full course
of chemotherapy. As a result, such patients may
have a higher chance of cancer recurrence and
shorter survival.
According to a large clinical trial, a new treatment
regimen prevents chemotherapy-related nausea
better than standard antinausea treatments
(this study was funded in part by a grant from
the NCI).78
Patients received olanzapine or
placebo, in combination with standard antinausea
treatments (aprepitant or fosaprepitant and a
5-hydroxytryptamine type 3-receptor [5HT3]
antagonist) on the day of chemotherapy and for
several days after chemotherapy. The patients were
being treated with cisplatin or cyclophosphamide–
doxorubicin, types of chemotherapy that often
trigger nausea.
In the first 24 hours after chemotherapy, the
proportion of patients who were nausea free was
much higher in the olanzapine group than in the
placebo group (74% v 45%), and over a 5-day
period after chemotherapy (37% v 22%).
These findings add to evidence from other
clinical trials suggesting the benefit of olanzapine
in preventing chemotherapy-related nausea and
vomiting. Olanzapine is approved by the FDA for
treatment of psychosis. The adverse effects typically
include mild short-term sedation, weight gain, and
increased risk of type 2 diabetes. In this study,
patients who received olanzapine had drowsiness on
the second day, which subsided in the subsequent
days. There were no serious adverse effects related
to olanzapine.
PATIENT SELF-REPORTING OF
SYMPTOMS IMPROVES CARE
Most patients with advanced cancer will
experience symptoms while receiving treatment.
Physicians or nurses typically ask patients about
their symptoms only during clinic visits, and
toxicity data in clinical trials are biased according
to selection of patients who enroll in the trials
(compared with the average patient in practice
who receives the drug) and by the limited nature
of gathering the data. As a result, symptoms that
are more common in patients who may not be
represented in the trials and that appear or change
between visits can be missed or simply forgotten
and can thus go untreated.
In the past several years, more efficient ways of
monitoring symptoms have been proposed. One
of these involves collecting symptom information
directly from patients through standardized
questionnaires, without physician interpretation.
VOICES OF CANCER RESEARCH
LORI WALLACE-PUSHINAITIS
“There are no
answers for some
patients with cancer.
And we’re not going
to find answers unless
research continues
to be funded.”
When Lori received her second breast cancer diagnosis in 2014, the
cancer had already spread throughout her body. However, despite
having advanced disease, Lori spent more than a year on a clinical trial
for lurbinectedin, seeing slow and steady improvement for 14 months
until the cancer began to grow again.
Still committed to exploring her options, Lori has moved on to other
treatments. She is grateful, however, as she feels clinical trials have
given her more time with her son.
Lori is a volunteer with the Bay Area Young Survivors (BAYS), Mets in
The City (MITC), Facing Our Risk of Cancer Empowered (FORCE),
Young Survival Coalition (YSC), and METAvivor.
CLINICAL CANCER ADVANCES 2017
37
This approach is part of a growing recognition
of the importance of patient-reported outcomes
in medicine and patient-centered health care
in general.
A large clinical trial recently showed how one
patient-reported outcome tool can have positive
effects on the well-being of patients with cancer.79
In the study, patients receiving chemotherapy for
advanced breast, genitourinary, gynecologic, or lung
cancer were randomly assigned to the self-reporting
group or the usual care group.
Self-reporting was conducted via a Web-based
questionnaire that covered 12 common symptoms,
such as appetite loss, constipation, cough, diarrhea,
and fatigue. The tool triggered e-mail alerts to
nurses whenever patients reported symptoms
worsening. Usual care consisted of discussing and
documenting symptoms during patients’ visits with
their oncologists.
Over a 6-month period, more patients in the
self-reporting group (34%) had an improvement
in health-related quality of life (HRQL) than in the
usual care group (18%). Conversely, fewer patients
in the self-reporting group (38%) had worsening
of HRQL than in the usual care group (53%). HRQL
measures mobility, self-care, usual activities, pain or
discomfort, anxiety, and depression. More studies
are needed to determine if symptom self-reporting
would have such a large benefit in other care
settings, but this and other studies have proven that
this technology holds promise in the supportive care
of patients receiving cancer treatment.
PATIENT NAVIGATION PROGRAM
IMPROVES COMPLIANCE WITH
CANCER THERAPY
The first patient navigation programs were
developed nearly three decades ago to improve
access to cancer screening. Since then, a variety
of such programs have been launched to help
people, particularly those in medically underserved
38
CLINICAL CANCER ADVANCES 2017
communities, overcome barriers to receiving
quality care—from diagnosis through treatment
and survivorship.
Patient navigators guide patients through all the
complexities of multidisciplinary cancer care. This
may include ensuring that patients schedule and
attend physician visits, start cancer therapy as soon
as possible, and take prescription medicines as
directed.
A recent report describes a navigation program
designed to reduce the challenges faced by
underserved minority patients with cancer.80
Although minority women in the United States are
less likely to develop breast cancer, they are more
likely to die as a result of breast cancer than white
women. The higher breast cancer death rate among
minority women results in part from treatment
delays and patients not sticking to treatment.
In the study, patients diagnosed with breast
cancer were paired with a patient navigator, while
a second group of patients received usual care (ie,
without the help of patient navigators). Most of
the patients were either African American (45%) or
Hispanic (38%), and 72% were enrolled in a program.
The navigators met with patients at all radiology
and oncology medical appointments, as well as
on the day of surgery. They also provided financial
consultations and helped negotiate payments,
as needed.
Patients who received help from patient
navigators began cancer treatment sooner than
those who received usual care and had better
compliance with treatment after surgery. On
average, women in the patient navigation group
started chemotherapy approximately 30 days
earlier and hormone therapy approximately 95
days earlier than those in the usual care group.
Patient compliance with either chemotherapy or
hormone therapy was 100% among women in the
navigation program. In contrast, among women
who received usual care, only 57% were compliant
with chemotherapy and 69% with hormone therapy.
These findings affirm that use of navigators within
cancer centers is vital to improving cancer care,
especially in medically underserved and vulnerable
populations.
ADDRESSING HEALTH LITERACY
IN THE ERA OF PRECISION MEDICINE
Genomics-based targeted cancer therapies
have had a major, positive effect on modern
cancer therapy. However, the ability to offer truly
personalized cancer care to most patients will
require lower costs for genomic testing and faster
sample processing times. Not all communities
and individuals have equal access to genomic
testing, and such testing may not even be clinically
informative for many patients. Another challenge
is that precision medicine and its associated
terminology are complex.
Recent research suggests that the public may
not fully understand the current possibilities and
limitations of genetic or genomic information,
including results of genetic testing. One reason
may involve the health literacy level of consumers,
meaning how much people do or don’t understand
health and medical information. For instance, one
study shows that understanding health information
is an important factor in how people perceive
the importance of genetic testing (this study
was funded in part by a grant from the NIH).81
Those with high health literacy scores tended to
understand the importance and implications of
genetic testing better than those who had low or
limited health literacy scores. These findings are
relevant whenever genetic testing is used to inform
patient care, regardless of disease.
In the study, researchers surveyed more than
600 patients at a primary health clinic of a large
hospital, which serves a diverse patient population
in the St Louis, Missouri, area. Participants were
asked to complete a written questionnaire followed
by a set of verbally administered questions to
measure their level of health literacy. The written
questionnaire covered knowledge of genetics,
participants’ confidence in their ability to use
genetic information, and perceived importance
of genetic information and family history. Most
participants were aware of the importance of family
health history and were sure they could talk about
it with family members; however, approximately half
of participants (47%) were found to have limited
health literacy.
People with limited health literacy had lower
genetics-related knowledge and lower awareness
of the value of knowing family health history. Those
with limited health literacy were more likely to think
that learning about their genetic information was
important, compared with those with adequate
health literacy; however, they were less likely to think
that family health history information was important.
Interestingly, people with limited health literacy
were more likely to discuss family health history
with their physicians than those with adequate
health literacy.
These findings underscore the need for education
programs to improve health literacy, particularly
with regard to genetics. An informed patient is able
to make better decisions regarding genetic testing
and screening and how these tools may be used to
inform his or her health care.
CLINICAL CANCER ADVANCES 2017
39
CANCER WORSENED IN MORE MEN IN THE ACTIVE SURVEILLANCE GROUP
than in men who received either surgery or radiation plus hormone therapy
Active
Surveillance
Surgery
cancer worsened
92%
EXCELLENT 10-YEAR SURVIVAL
FOR PATIENTS WITH EARLY PROSTATE
CANCER, REGARDLESS OF TREATMENT
One in eight men will be diagnosed with prostate
cancer at some point during his lifetime. In 2016
alone, an estimated 181,000 men received a prostate
cancer diagnosis.82 In recent decades, widespread
prostate-specific antigen (PSA) testing has
increased prostate cancer diagnoses and treatment.
However, because prostate cancer often grows
slowly, many men who are diagnosed with early
cancer die as a result of other causes before they
succumb to prostate cancer. This means that
treatment of early prostate cancer is not always
necessary. Prostate cancer treatment may also
cause complications, such as sexual, urinary, and
bowel problems.
In addition, the choice of treatment for men
with prostate cancer that is detected on the basis
of PSA testing is controversial. A recent clinical
trial provided answers to a long-standing question
in prostate cancer care: which approach is best
in treating localized, early-stage prostate cancer:
surgery, radiation therapy, or active surveillance?83
The trial randomly assigned 1,643 men diagnosed
with localized prostate cancer to either active
surveillance, surgery (radical prostatectomy),
or radiation therapy with short-course hormone
therapy. PSA levels were regularly measured in men
assigned to active surveillance, and those with rising
40
CLINICAL CANCER ADVANCES 2017
cancer worsened
8%
20%
80%
Chemotherapy
cancer worsened
8%
92%
PSA levels had the option of continuing surveillance
or receiving curative therapy, including surgery and
radiation therapy.
After a median follow-up period of 10 years,
there were no significant differences among the
three groups in rate of prostate cancer-related
deaths (approximately 1%). Similarly, there were
no differences in the number of deaths resulting
from any cause. However, cancer had worsened in
more men in the active surveillance group (20%)
than in men who received either surgery (8%)
or radiation therapy plus hormone therapy (8%).
Likewise, the rate of metastasis was higher in the
active surveillance group (6%) than in either the
surgery (2%) or radiation therapy plus hormone
therapy group (3%).
This trial addresses the important question
of clinical effectiveness regarding these three
approaches to treating early, localized prostate
cancer. Although the findings suggest that
immediate active treatment is more effective than
active surveillance to avoid disease worsening,
longer follow-up may be needed to see if there
are differences in death rates across the three
approaches. Meanwhile, the insights from this
study will inform treatment discussions between
physicians and patients.
XXFor additional notable advances in patient
care, please see Appendix Table A1.
u
ADVAN C ES I N TU M O R B IO LOGY
The biology of a cancer is constantly changing. New genetic mutations
appear as the tumor grows and spreads, providing new challenges for
treatment and also new avenues of research for the development of additional
therapies. In 2016, a landmark study provided an in-depth view of the pattern
of genetic changes during development of melanoma from precursor lesions
(precancer).
Cancers can also develop new genetic mutations that make them resistant to
cancer therapy. Two early studies suggested that matching genetic changes in
the tumor with specific treatments that target those genetic changes improves
outcomes for patients with advanced cancer.
CLINICAL CANCER ADVANCES 2017
41
MELANOMA DEVELOPS THROUGH
SUCCESSIVE GENETIC CHANGES
THERAPEUTIC OPTIONS EXPAND WITH
PRECISION MEDICINE APPROACHES
Prior large-scale studies of genetic mutations in
melanoma focused mostly on advanced cancers.
As a result, the order in which distinct genetic
mutations arise as melanoma progresses from
benign skin lesions (eg, melanocytic nevi or moles)
is not well understood. Detailed knowledge about
the genetic changes that occur as melanoma
develops from precancerous lesions would improve
both diagnosis and prognosis for this cancer.
A new analysis of 293 cancer-related genes from
37 primary melanomas and precancerous lesions
revealed that distinct genetic changes emerge in
a stepwise fashion as melanoma develops, grows,
and spreads (this study was funded in part by a
grant from the NIH).84
For example, benign skin
tumors harbored only BRAF V600E mutations,
whereas intermediate precancerous lesions also had
mutations in NRAS and other genes. Changes in
the CDKN2A gene appeared exclusively in invasive
melanomas, and mutations in PTEN and TP53
occurred only in advanced melanomas.
The study also confirmed that UV light is a major
factor in both the initial development of melanoma
and its progression from early to advanced stage.
Researchers found so-called mutational signatures
unique to UV radiation exposure across all stages,
from benign tumors to invasive melanoma. The
frequency of UV light–related mutations increased
as the cancer became more advanced. The findings
from this landmark study establish a foundation for
refining the criteria involved in melanoma diagnosis
and prognosis.
Sadly, almost every patient with advanced
cancer eventually reaches a point when there are
no effective treatments left. In the current era of
precision medicine, however, molecular testing of
the tumor is opening additional treatment options
for some of these patients.
One recent study supports the use of
comprehensive genomic testing in patients who
have hard-to-treat cancers. Researchers analyzed
changes in 236 genes from the tumors of more
than 300 patients with different cancers.85 Socalled actionable mutations, or mutations that could
be targeted with an existing therapy, were found
in nearly all patients (93%), and 38% received a
therapy matched to the mutation. Patients with
more actionable mutations and matched therapies
had more frequent and longer remissions, as well as
longer survival.
An ongoing trial is assigning patients with
advanced cancer whose prior genetic tests revealed
abnormalities in specific molecular pathways
to corresponding targeted treatments.86 The
treatment assignments are outside of FDA-approved
indications. Tumors shrank in 29 (22%) of the first
129 patients enrolled in the study; these patients had
12 different types of cancer.
42
CLINICAL CANCER ADVANCES 2017
XXFor additional notable advances in tumor
biology, please see Appendix Table A1.
u
LOO KIN G TO TH E FUTU RE
LIQUID BIOPSIES HELP PERSONALIZE CANCER THERAPY
Nearly every patient with suspected cancer will undergo a tumor
biopsy. In fact, tumor biopsy is the main way physicians diagnose most types
of cancer and determine their grade or stage. In addition, biopsies can also
be used to make treatment decisions. By analyzing the genetic material in the
tumor specimen, physicians may uncover genetic changes that can be matched
to specific targeted therapies. However, although tumor biopsy has been a
critical part of cancer care for decades, depending on the location of the tumor
and the patient’s general health, performing a tumor biopsy may not always be
feasible or safe.
CLINICAL CANCER ADVANCES 2017
43
Physicians have followed circulating tumor
biomarkers to monitor patient status for decades,
including carcinoembryonic antigen (CEA), cancer
antigen 125 (CA-125), CA 15-3/CA 27.29, CA 19-9,
and PSA for colorectal, ovarian, breast, pancreatic,
and prostate cancers, respectively. Over the last
15 years, strategies to capture and enumerate
circulating tumor cells have also been reported.
More recently, several investigators have reported
the ability to purify and characterize circulating,
cell-free tumor DNA. These approaches have been
dubbed liquid biopsies. They offer the opportunity
to easily and conveniently determine changes in
both the amount of tumor burden and the genotype
and phenotype of the cancer over time.
In a liquid biopsy, circulating tumor DNA is
collected from bodily fluids and analyzed, providing
what seems to be representative information about
genetic changes in the tumor. Because genetic
changes evolve as cancers grow and spread, this
information can be used to stop a treatment to
which resistance is emerging, as has been done
with circulating proteins and tumor cells for years,
or, perhaps more exciting, to switch to a different
treatment that is tailored to a different mutation as
it appears.
Even for patients who are able to undergo a
traditional tissue biopsy, a liquid biopsy may be
safer, quicker, and more convenient—and perhaps
even more informative. For example, a biopsy only
represents a single site of disease, and studies of
tumor heterogeneity tell us that different tumor
sites in the same patient may have different
genotypes and phenotypes. Thus, a liquid biopsy
may provide a snapshot of the tumor makeup of the
entire body, not just that of the biopsied site.
Another advantage of a liquid biopsy is its
potential to provide a snapshot of the full landscape
of genetic changes present in a tumor. Different
parts of the tumor often have genetically distinct
groups of cells. Because a tissue biopsy takes only
a small piece of the tumor, some key mutations
may be missed. Nonetheless, research also shows
that liquid biopsies sometimes fail to detect key
mutations that are revealed by tissue biopsy tests.
44
CLINICAL CANCER ADVANCES 2017
Liquid biopsy informs lung cancer treatment
decisions. One liquid biopsy test has already
become part of routine care for patients with
advanced lung cancer, and others are being
developed using a variety of technologies. The test
screens circulating tumor DNA from the blood for
a specific mutation in the EGFR gene: T790M. This
mutation occurs in approximately 60% of patients
who develop resistance to epidermal growth factor
receptor (EGFR)-targeted drugs, afatinib, gefitinib,
and erlotinib.
It is important to know whether a patient has
the T790M mutation because new treatments that
specifically target this genetic change are available
(eg, osimertinib and rociletinib). However, patients
who do not have the T790M mutation should not
receive such treatments, because they are less
effective against T790M-negative tumors.
Tumor testing for T790M is now recommended
for all patients with EGFR-positive NSCLC that
worsens despite EGFR-targeted therapy. However,
many patients are not able to have the test done;
the tumor may be in an inaccessible location, there
may be insufficient tissue available, or a biopsy
may not be safe because the patient is in poor
health. For such patients, a liquid biopsy test is
now available. The blood test, known as cobas
EGFR Mutation Test v2, was FDA approved in
2015 to identify patients who may benefit from
osimertinib.87 In 2016, the test was also approved
for use as a companion diagnostic to help identify
patients with a different type of EGFR mutation who
may benefit from initial treatment with erlotinib.88
In an early study, the liquid biopsy test identified
six in 10 patients who had T790M-positive tumors.89
This is good news for patients who are unable to
undergo a traditional tissue biopsy.
Meanwhile, several other promising liquid biopsy
tests for patients with lung cancer are being
explored. A blood test using a technique known as
BEAMing identified seven of 10 patients with T790M
mutations in their tumors (this study was funded in
part by a grant from the NIH).90
A different test
that uses so-called droplet digital polymerase chain
reaction identified eight of 10 patients with T790M-
positive tumors (this study was funded by a grant
from the NCI).91
The latter test can also screen
for other EGFR as well as KRAS mutations.
Finally, another early clinical trial found that
response to the EGFR-targeted therapy rociletinib
was similar irrespective of whether T790M status
was determined through traditional tissue biopsy or
liquid biopsy of urine or blood. The researchers used
BEAMing technology for blood mutation analysis and
a technique known as short footprinting for urine.
Blood and urine testing identified several T790Mpositive cases that were missed by tissue biopsy.92,93
These studies confirm that the accuracy of
molecular testing using either blood or urine
samples is high and that such testing predicts
outcomes from EGFR therapy similar to those
predicted by traditional tumor biopsy.90,94 Moreover,
early findings show that regardless of how the
T790M mutation is detected (liquid or traditional
tumor biopsy), patients respond to osimertinib and
rociletinib equally well.
However, a negative liquid biopsy test is not as
reliable as a negative tumor biopsy test. Therefore,
whenever possible, patients with a negative blood
or urine test should have tumor tissue tested for
confirmation.
Liquid biopsy may open new targeted treatment
options. Another liquid biopsy test was reported
last year that could rapidly and accurately screen
blood samples for a broad panel of genetic changes,
including EGFR T790M.95 An analysis of blood
samples from 15,000 patients with 50 different
types of cancer showed that the patterns of genetic
changes in circulating tumor DNA were similar to
those in the tumor.
The blood test detected 94% to 100% of changes
in EGFR, BRAF, KRAS, ALK, RET, and ROS1 genes
that had been found previously in tumor biopsy
analyses from the same patients. It also provided
leads for targeted therapy that could be matched to
the genetic changes found in the circulating tumor
DNA. The researchers identified such additional
treatment opportunities for approximately twothirds of patients who had insufficient tissue
available for a biopsy.
Liquid biopsy predicts colon cancer recurrence. In
2016, researchers proposed an entirely different
use for liquid biopsies. According to a large study,
measuring circulating tumor DNA from the blood
can accurately predict which patients with stage II
colon cancer are at risk for recurrence (this study
was funded in part by a grant from the NIH).96
Detection of circulating tumor DNA after colon
cancer surgery is a sign that some cancer cells have
been left behind, and this puts the patient at higher
risk of recurrence.
Overall, patients with stage II colon cancer have
a low risk of recurrence, and four of five are cured
with surgery alone. Patients who are at high risk
of recurrence may need additional treatment after
surgery to lower the chances of recurrence. This
new blood test may help identify more patients
who might benefit from receiving chemotherapy
after surgery.
In the study, nearly 80% of patients who had
circulating tumor DNA detected in the blood after
surgery experienced a recurrence of colon cancer. In
contrast, only 10% of patients who tested negative
for circulating tumor DNA experienced a recurrence.
These findings are relevant to more than 300,000
people around the world who are diagnosed with
stage II colon cancer each year.
EXPANDING TARGETED THERAPY
OPTIONS FOR OVARIAN CANCER
Worldwide, more women die from ovarian
cancer than from any other gynecologic cancer.
Although initial treatment of ovarian cancer with
chemotherapy is usually effective, most patients will
eventually experience a recurrence. Patients with
recurrent ovarian cancer have limited treatment
options, and median survival is generally reported as
between 1 and 2 years from diagnosis.
Standard treatments for recurrent ovarian cancer
include bevacizumab, which halts cancer growth
for approximately 3 months, and the novel targeted
treatment olaparib. Olaparib was the first treatment
in a new class of targeted therapies that block PARP,
a protein that repairs damaged DNA. Although
olaparib is more effective than bevacizumab, it is
only approved for use in patients with BRCA gene
mutations, who account for just 10% to 15% of all
women with ovarian cancers.
In 2016, researchers reported that a different
PARP inhibitor, niraparib, is effective in a broader
range of patients with advanced, recurrent ovarian
cancer.97 The late-stage clinical trial included two
groups of patients: women with germline (heritable)
BRCA mutations and those without such mutations.
Within the group lacking a BRCA mutation, there
was a subset of patients with another defect in DNA
repair processes called homologous recombination
DNA repair deficiency (HRD). All patients had
ovarian cancer that responded to platinumcontaining chemotherapy.
The patients were randomly assigned to receive
niraparib or placebo. Niraparib slowed cancer
growth in all patient groups, but it was most
effective in patients with BRCA mutations. In this
group, the median time until the cancer worsened
was 21 months with niraparib and 5.5 months with
placebo. Among patients without BRCA mutations,
cancer worsened after a median period of 9.3
months with niraparib, compared with 3.9 months
with placebo. In the subset of patients with HRD, the
CLINICAL CANCER ADVANCES 2017
45
median time to cancer progression was 12.9 months
with niraparib and 3.8 months with placebo.
The most common severe adverse effects related
to niraparib included low blood counts and anemia.
Patients who received niraparib reported a quality
of life comparable to that reported by those who
received placebo.
These findings suggest that the benefit of
niraparib is not restricted to patients with a known
germline BRCA mutation, expanding access to PARP
inhibitors. However,
further work is needed
to determine the most
appropriate strategy for
use of PARP inhibitors in
this population.
with cancer to become our shared and primary
focus. President Obama and Biden challenged the
cancer community to unite and work together in
recognition that the whole will be far greater than
the sum of its parts. The Cancer Moonshot also
addressed the entire continuum of cancer care to
speed advances in cancer prevention, diagnosis,
treatment, supportive care, survivorship, and endof-life care. Biden made an important decision to
include all types of cancer.
The Cancer Moonshot
Initiative spurred public
and private sector
organizations into
action and jumpstarted
collaborations to
accelerate the nation’s
CANCER
progress in fighting
MOONSHOT:
life-threatening cancers
GALVANIZING
that affect so many. To
A RENEWED
continue the momentum
COMMITMENT TO
Joe Biden,
in our work to conquer
CONQUERING
Former US Vice President
cancer, ASCO has urged
CANCER
Congress and the new
During his final State
Administration to take the
Every year, thousands of oncologists and
of the Union address,
following steps:
millions of patients all over the world await
President Obama
XX Advance initiatives
the news coming from [the ASCO Annual
launched the Cancer
to improve
Meeting] ... new breakthroughs, new
Moonshot to renew the
interoperability
therapies, new promises of cure, hope….
nation’s commitment
of health care
I know of no cadre of people in the world
to conquering cancer.
information, which
Led by Vice President
will help improve
more desperately in need of hope than the
Joe Biden, the National
patient care and
16 million people with cancer.
Cancer Moonshot
support quality
Initiative aligned the
measurement and
resources of the federal
research.
government to accelerate progress in cancer
XXIdentify ways to streamline regulatory and
research and encouraged greater collaboration
reporting requirements so researchers can
within the entire cancer research community.
spend less time on administrative tasks and
Throughout 2016, Biden met with a wide range
more time on developing new ideas and
of stakeholders to better understand the current
conducting research.
cancer research and cancer clinical practice
XXProvide federal funding for the Cancer
environment—both opportunities in and barriers
Moonshot Initiative and other translational and
to providing cancer care and conducting cancer
clinical research efforts.
research in the United States. Working with the
Cancer Moonshot Task Force (which included
ASCO is particularly pleased that the Cancer
representatives from all federal agencies involved
Moonshot Task Force highlighted the continuing
in cancer clinical care and research), Biden made a
work of the FDA with ASCO and Friends of Cancer
series of announcements to take immediate action
Research to evaluate clinical trial entrance criteria
to improve cancer research.
that may unnecessarily restrict clinical trial access,
ASCO worked closely with Biden’s Moonshot
such as such as brain metastases, HIV status, organ
team, submitting recommendations to Biden, the
dysfunction, and age restrictions.
Task Force, and NCI Blue Ribbon Panel; speaking
at public forums; engaging in strategic discussions;
With the backing of the new Congress and
and welcoming Biden to address the world’s cancer
Administration, we can build on the progress
leaders who convened at the ASCO Annual Meeting
of the Cancer Moonshot and make gains in
in Chicago in June 2016.
our fight against cancer.
The Cancer Moonshot rightly called for patients
“
”
46
CLINICAL CANCER ADVANCES 2017
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68. Venook AP, Niedzwiecki D, Innocenti F, et al: Impact of
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CLINICAL CANCER ADVANCES 2017
49
APPENDIX
Table A1. Additional Notable Advances (October 2015 – October 2016)
Area of Research
Prevention
and
Screening
Treatment
50
Study Title
Reference
Lung cancer risk and demographic characteristics of current 20-29
pack-year smokers: Implications for screening
Pinsky PF, et al: J Natl Cancer
Inst 107:djv226, 2015
Lung cancer incidence and mortality in National Lung Cancer
Screening Trial participants who underwent low-dose prevalence
CT screening: A retrospective cohort analysis of a randomized,
multicenter, diagnostic screening trial
Patz EF Jr, et al: Lancet Oncol
17:590-599, 2016
Adjunct screening with tomosynthesis or ultrasound in women
with mammography-negative dense breasts: Interim report of a
prospective comparative trial
Tagliafico AS, et al: J Clin Oncol
34:1882-1888, 2016
BERIL-1: A phase II, placebo-controlled study of buparlisib (BKM120)
plus paclitaxel in patients with platinum-pretreated recurrent/
metastatic head and neck squamous cell carcinoma (HNSCC)
Soulieres D, et al: J Clin Oncol
34, 2016 (suppl; abstr 6008)
Dabrafenib plus trametinib in patients with previously treated
BRAFV600E-mutant metastatic nonsmall cell lung cancer: An openlabel, multicentre phase 2 trial
Planchard D, et al: Lancet Oncol
17:642-650, 2016
Safety and efficacy of single-agent rovalpituzumab tesirine
(SC16LD6.5), a delta-like protein 3 (DLL3)-targeted antibody-drug
conjugate (ADC) in recurrent or refractory small cell lung cancer
(SCLC)
Rudin CM, et al: J Clin Oncol 34,
2016 (suppl; abstr LBA8505)
Efficacy and safety of crizotinib in patients (pts) with advanced MET
exon 14-altered nonsmall cell lung cancer (NSCLC)
Drilon AE, et al: J Clin Oncol 34,
2016 (suppl; abstr 108)
Overall survival and durable responses in patients with BRAF v600–
mutant metastatic melanoma receiving dabrafenib combined with
trametinib
Long GV, et al: J Clin Oncol
34:871-878, 2016
Ibrutinib as initial therapy for patients with chronic lymphocytic
leukemia
Burger JA, et al: N Engl J Med
373:2425-2437, 2015
Lazarus-type response to crizotinib in a patient with poor
performance status and advanced met exon 14 skipping mutationpositive lung adenocarcinoma
Shea M, et al: J Thorac Oncol
11:e81-e82, 2016
Comparison of dabrafenib and trametinib combination therapy with
vemurafenib monotherapy on health-related quality of life in patients
with unresectable or metastatic cutaneous BRAF Val600-mutationpositive melanoma (COMBI-v): Results of a phase 3, open-label,
randomized trial
Grob JJ, et al: Lancet Oncol
16:1389-1398, 2015
Olaratumab and doxorubicin versus doxorubicin alone for treatment
of soft-tissue sarcoma: An open-label phase 1b and randomized
phase 2 trial
Tap WD, et al: Lancet Oncol
388:488-497, 2016
Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy
Ravaud A, et al: N Engl J Med
[epub ahead of print on October
9, 2016]
Pembrolizumab for patients with PD-L1-positive advanced gastric
cancer (KEYNOTE-012): A multicentre, open-label, phase 1b trial
Muro K, et al: Lancet Oncol
17:717-726, 2016
Safety and efficacy of PD-1 blockade using pembrolizumab in
patients with advanced soft tissue (STS) and bone sarcomas (BS):
Results of SARC028 – a multicenter phase II study
Tawbi HAH, et al: J Clin Oncol
34, 2016 (suppl; abstr 11006)
Nivolumab (nivo) vs. investigator’s choice (IC) for recurrent or
metastatic (R/M) head and neck squamous cell carcinoma (HNSCC):
CheckMate-141
Gillison ML, et al: Presented
at the American Association
for Cancer Research Annual
Meeting, New Orleans, LA, April
16-20, 2016
Preliminary results from KEYNOTE-055: Pembrolizumab after
platinum and cetuximab failure in head and neck squamous cell
carcinoma (HNSCC)
Bauml J, et al: J Clin Oncol 34,
2016 (suppl; abstr 6011)
Results of a phase III randomized, multicenter study of allogeneic
stem cell transplantation after high vs. reduced intensity conditioning
in patients with myelodysplastic syndrome (MDS) or acute myeloid
leukemia
Scott BL, et al: Blood 126, 2015
(abstr LBA-8)
CLINICAL CANCER ADVANCES 2017
APPENDIX
Table A1. Additional Notable Advances (October 2015 – October 2016) continued
Area of Research
Treatment
(continued)
Study Title
Reference
PET-CT surveillance versus neck dissection in advanced head and
neck cancer
Mehanna H, et al: N Engl J Med
374:1444-1454, 2016
Local consolidative therapy (LCT) to improve progression-free
survival (PFS) in patients with oligometastatic nonsmall cell lung
cancer (NSCLC) who receive induction systemic therapy (IST):
Results of a multi-institutional phase II randomized study
Gomez DR, et al. J Clin Oncol 34,
2016 (suppl; abstr 9004)
A randomized controlled trial evaluating resection of the primary
breast tumor in women presenting with de novo stage IV breast
cancer: Turkish study (protocol MF07-01)
Soran A, et al: J Clin Oncol 34,
2016 (suppl; abstr 1005)
Locoregional treatment versus no treatment of the primary tumor in
metastatic breast cancer: An open-label randomized controlled trial
Badwe R, et al: Lancet Oncol
16:1380-1388, 2015
Watch-and-wait approach versus vs. surgical resection after
chemoradiotherapy for patients with rectal cancer (the OnCoRe
project): A propensity-score matched cohort analysis
Renehan AG, et al: Lancet Oncol
17:174-183, 2016
National trends in nonoperative management of rectal
adenocarcinoma
Ellis CT, et al: J Clin Oncol
34:1644-1651, 2016
Neurotoxic effects of anthracycline- vs. nonanthracycline-based
chemotherapy on cognition in breast cancer survivors
Kesler SR, et al: JAMA Oncol
2:185-192
The MITO8 phase III international multicenter randomized study
Pignata S, et al: J Clin Oncol 34,
testing the effect on survival of prolonging platinum-free interval
2016 (suppl; abstr 5505)
(PFI) in patients with ovarian cancer (OC) recurring between 6 and 12
months after previous platinum-based chemotherapy: A collaboration
of MITO, MANGO, AGO, BGOG, ENGOT, and GCIG
Nanoliposomal irinotecan with fluorouracil and folinic acid in
metastatic pancreatic cancer after previous gemcitabine-based
therapy (NAPOLI-1): Aglobal, randomized, open-label, phase III trial
Wang-Gillam A, et al: Lancet
387:545-557, 2016
Cardioprotection and safety of dexrazoxane in patients treated for
newly diagnosed T-cell acute lymphoblastic leukemia or advancedstage lymphoblastic non-Hodgkin lymphoma: A report of the
Children’s Oncology Group randomized trial Pediatric Oncology
Group 9404
Asselin BL, et al: J Clin Oncol
34:854-862, 2016
Intravenous pegylated asparaginase versus intramuscular native
Escherichia coli l-asparaginase in newly diagnosed childhood acute
lymphoblastic leukemia (DFCI 05-001): A randomized, open-label
phase III trial
Place AE, et al: Lancet Oncol
16:1677-1690, 2015
Efficacy of busulfan-melphalan high dose chemotherapy
consolidation (BuMel) in localized high-risk Ewing sarcoma (ES):
Results of EURO-EWING 99-R2 randomized trial (EE99R2Loc)
Whelan J, et al: J Clin Oncol 34,
2016 (suppl; abstr 11000)
Predictors of recurrence during years 5-14 in 46,138 women with ER+
breast cancer allocated 5 years only of endocrine therapy (ET)
Pan H, et al: J Clin Oncol 34,
2016 (suppl; abstr 505)
Continuous combined estrogen plus progestin and endometrial
cancer: The Women's Health Initiative randomized trial
Chlebowski RT, et al: J Natl
Cancer Inst 108: pii: djv350, 2015
A phase III randomized controlled trial of short-course radiotherapy
with or without concomitant and adjuvant temozolomide in elderly
patients with glioblastoma (CCTG CE.6, EORTC 26062-22061, TROG
08.02, NCT00482677)
Perry JR, et al: J Clin Oncol 34,
2016 (suppl; abstr LBA2)
Effect of chemoradiotherapy vs. chemotherapy on survival in patients
with locally advanced pancreatic cancer controlled after 4 months of
gemcitabine with or without erlotinib the lap07 randomized clinical
trial
Hammel P, et al: JAMA 15:18441853, 2016
Dexamethasone and supportive care with or without whole brain
radiotherapy in treating patients with nonsmall cell lung cancer with
brain metastases unsuitable for resection or stereotactic radiotherapy
(QUARTZ): Results from a phase III, noninferiority, randomized trial
Mulvenna P, et al: Lancet [epub
ahead of print on September 4,
2016]
Radiotherapy with 4 gy × 5 vs. 3 gy × 10 for metastatic epidural spinal
cord compression: Final results of the Score-2 trial (aro 2009/01)
Rades D, et al: J Clin Oncol
34:597-602, 2016
CLINICAL CANCER ADVANCES 2017
51
APPENDIX
Table A1. Additional Notable Advances (October 2015 – October 2016) continued
Area of Research
Treatment
(continued)
Patient Care
52
Study Title
Reference
5-year results of accelerated partial breast irradiation using sole
interstitial multicatheter brachytherapy vs. whole-breast irradiation
with boost after breast-conserving surgery for low-risk invasive
and in-situ carcinoma of the female breast: A randomized, phase III,
noninferiority trial
Strnad V, et al: Lancet 387:229238, 2016
Clinical activity and safety of cobimetinib (cobi) and atezolizumab in
colorectal cancer (CRC)
Bendell JC, et al: J Clin Oncol 34,
2016 (suppl; abstr 3502)
Local consolidative therapy (LCT) to improve progression-free
survival (PFS) in patients with oligometastatic nonsmall cell lung
cancer (NSCLC) who receive induction systemic therapy (IST):
Results of a multi-institutional phase II randomized study
Gomez DR, et al: J Clin Oncol
34, 2016 (suppl; abstr 9004)
Efficacy, safety, and health-related quality of life (HRQoL) of
regorafenib in patients with hepatocellular carcinoma (HCC)
progressing on sorafenib: Results of the international, double-blind
phase III RESORCE trial
Bruix J, et al: Presented at
the European Society for
Medical Oncology Conference,
Copenhagen, Denmark, October
7-11, 2016
Randomized trial of an inpatient palliative care intervention in
patients hospitalized for hematopoietic stem cell transplantation
(HCT)
El-Jawahri A, et al: J Clin Oncol
34, 2016 (suppl; abstr 10004)
Discussions of life expectancy and changes in illness understanding
in patients with advanced cancer
Epstein AS, et al: J Clin Oncol
34:2398-2403, 2016
Overall survival in patients with lung cancer using a web-applicationguided follow up compared with standard modalities: Results of
phase III randomized trial
Denis F, et al: J Clin Oncol 34,
2016 (suppl; abstr LBA9006)
Patient income level and cancer clinical trial participation
Unger JM, et al: JAMA Oncol
2:137-139, 2016
Financial burden of cancer clinical trial participation and the impact
of a cancer care equity program
Nipp RD, et al: Oncologist
21:467-474, 2016
Impact of lower limb lymphedema on quality of life in gynecologic
cancer survivors after pelvic lymph node dissection
Kim SI, et al: Eur J Obstet
Gynecol Reprod Biol 192:31-36,
2015
Association of financial strain with symptom burden and quality of
life for patients with lung or colorectal cancer
Lathan CS, et al: J Clin Oncol
34:1732-1740, 2016
Prospective validation of a 21-gene expression assay in breast cancer
Sparano JA, et al: N Engl J Med
373:2005-2014, 2015
Routine molecular profiling of patients with advanced non-small-cell
lung cancer: Results of a 1-year nationwide program of the French
Cooperative Thoracic Intergroup (IFCT)
Barlesi F, et al: Lancet 387:14151426, 2016
Patient-reported outcomes with anastrozole vs. tamoxifen for
postmenopausal patients with ductal carcinoma in situ treated with
lumpectomy plus radiotherapy (NSABP B-35): A randomized, doubleblind, phase III clinical trial
Ganz PA, et al: Lancet 387:857865, 2016
CLINICAL CANCER ADVANCES 2017
APPENDIX
Table A1. Additional Notable Advances (October 2015 – October 2016) continued
Area of Research
Tumor
Biology
Study Title
Reference
Plasma ESR1 mutations and the treatment of estrogen receptor–
positive advanced breast cancer
Fribbens C, et al: J Clin Oncol
34:2961-2968, 2016
HER2 expression identifies dynamic functional states within
circulating breast cancer cells
Jordan NV, et al: Nature 537:102106
Single-cell analysis of mixed-lineage states leading to a binary cell
fate choice
Olsson A, et al: Nature 537:698702
Adverse clinical outcome associated with mutations that typify
African American colorectal cancers
Wang Z, et al: J Natl Cancer Inst
108:pii: djw164, 2016
Inherited DNA-repair gene mutations in men with metastatic prostate
cancer
Pritchard ML, et al: N Engl J Med
375:443-453, 2016
Integrative clinical sequencing in the management of refractory or
relapsed cancer in youth
Mody RJ, et al: JAMA 314:913925, 2015
Diagnostic yield of clinical tumor and germline whole-exome
sequencing for children with solid tumors
Parsons DW, et al: JAMA Oncol
2:616-624, 2016
Multicenter feasibility study of tumor molecular profiling to inform
therapeutic decisions in advanced pediatric solid tumors the
individualized cancer therapy (ICAT) study
Harris MH, et al: JAMA Oncol
2:608-615, 2016
The molecular taxonomy of primary prostate cancer
Abeshouse A, et al: Cell 163:10111025, 2015
DNA-repair defects and olaparib in metastatic prostate cancer
Mateo J, et al: N Engl J Med
373:1697-1708, 2015
CLINICAL CANCER ADVANCES 2017
53
Table A2. ASCO Clinical Practice Guidelines, Updates, Endorsements and Adaptations from
January to October 2016
Publication Date
GUIDELINES
April 1, 2016
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage
Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline
March 23, 2016
Endocrine Therapy for Hormone Receptor–Positive Metastatic Breast Cancer: American Society of
Clinical Oncology Guideline
May 25, 2016
Management and Care of Women With Invasive Cervical Cancer: American Society of Clinical Oncology
Resource-Stratified Clinical Practice Guideline
May 31, 2016
Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline
May 31, 2016
Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical
Practice Guideline
May 31, 2016
Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline
July 25, 2016
Management of Chronic Pain in Survivors of Adult Cancers: American Society of Clinical Oncology
Clinical Practice Guideline
August 8, 2016
Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic
Oncology and American Society of Clinical Oncology Clinical Practice Guideline
August 15, 2016
Society of Surgical Oncology–American Society for Radiation Oncology–American Society of Clinical
Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast
Irradiation in Ductal Carcinoma in Situ
October 12, 2016
Secondary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified
Clinical Practice Guideline
February 16, 2016
Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: American
Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression
September 20, 2016
Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for
Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update
October 31, 2016
Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology
Clinical Practice Guideline Update
UPDATES
ENDORSEMENTS
February 16, 2016
Active Surveillance for the Management of Localized Prostate Cancer (Cancer Care Ontario Guideline):
American Society of Clinical Oncology Clinical Practice Guideline Endorsement
March 21, 2016
Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage,
Operable Breast Cancer: American Society of Clinical Oncology Endorsement of Cancer Care Ontario
Guideline Recommendations
March 21, 2016
Guideline on Muscle-Invasive and Metastatic Bladder Cancer (European Association of Urology
Guideline): American Society of Clinical Oncology Clinical Practice Guideline Endorsement
ADAPTATION
April 18, 2016
54
Selection of Optimal Adjuvant Chemotherapy Regimens for Early-Stage Breast Cancer and Adjuvant
Targeted Therapy for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancers: An
American Society of Clinical Oncology Guideline Adaptation of the Cancer Care Ontario Clinical
Practice Guideline
CLINICAL CANCER ADVANCES 2017
INDEX OF ADVANCES BY CANCER TYPE
u Bladder Cancer
12
u Blood Cancers and Lymphoma
14, 27, 28, 32, 51
u Brain Cancer
u Breast Cancer
31, 51
24, 28, 33, 38, 51, 52, 53
u Cervical Cancer
24
u Childhood Cancers
u Colon and Rectal Cancers
u
17, 22, 31, 51, 53
16, 31, 33, 45, 51, 52, 53
Endometrial Cancer
51
u Head and Neck Cancer
13, 51
u Kidney Cancer
29
u Liver Cancer
52
u Lung Cancer
11, 27, 44, 51, 52
u Melanoma and Other Skin Cancers
10, 18, 23, 42, 50
u Ovarian Cancer
14, 20, 30, 45, 51
u Pancreatic Cancer
21, 32, 51, 52
u Prostate Cancer
40, 53, 54
u Sarcoma50
CLINICAL CANCER ADVANCES 2017
55
STAY INFORMED
With the Latest Resources From ASCO
Metastatic Breast Cancer
What is metastatic
breast cancer?
Metastatic breast cancer is breast cancer that has
spread to other parts of the body. The most frequent
sites are bones, lymph nodes, liver, lungs, and brain.
It is still called breast cancer, even after it had spread.
Metastatic breast cancer is not curable, but it is
treatable. Many patients continue to live well for a
number of years with metastatic breast cancer.
How can I cope with metastatic
breast cancer?
A diagnosis of metastatic breast cancer often comes as a
shock. People describe a range of emotions such as fear,
anger, or sadness that may change day-to-day or over
time. You may have concerns about how this diagnosis will
affect many different aspects of your life, such as your
relationships, work or career, family and social roles, and
finances. You may be worried about suffering or having your
life shortened by this disease. It is important to remember you are not alone.
Cancer
Survivorship
Becoming informed about your specific diagnosis and working with your health care team to find professionals who can provide support to you
and your family, offer guidance about your treatment options, and identify services to address the needs of your caregivers are key parts of the
coping process. Talk openly with your doctors and health care team to express your feelings, preferences, and concerns. They are there to help,
and many team members have special skills, experience, and knowledge to support patients and their families.
How is metastatic breast cancer treated?
The primary goal of treatment for metastatic breast cancer is to extend or prolong life and to relieve the symptoms caused by the cancer.
This approach, aimed at reducing symptoms and suffering, is often referred to as supportive or palliative care, and it is often given along with
treatment to slow or stop the growth of cancer.
Advanced Cancer
Care Planning
A Decision-Making Guide for Patients
and Families Facing Serious Illness
Trusted Information About Life
After Treatment From the American
Society of Clinical Oncology
Treatment options for women with metastatic breast cancer vary based on characteristics of the tumor—for example, whether the tumor
is hormonally sensitive (ER-positive, PR-positive) or HER2-positive, where in the body the cancer has spread, the presence of specific
symptoms, and previous cancer treatments. For women with ER- and PR-positive cancers, treatment with hormonal therapy is effective and
can be used to control breast cancer for many years. Other common treatments for metastatic breast cancer include chemotherapy and
targeted therapy. Because it is not unusual for metastatic breast cancer to become resistant (stop responding) to these drugs, you may
need to change therapies fairly often. When making treatment decisions, you may also consider a clinical trial; talk with your doctor often
about all treatment options and the goals of each treatment.
Other possible treatments include radiation therapy or non-chemotherapy medications called bisphosphonates to treat bone
metastases and surgery to remove a tumor that is causing discomfort. You may receive additional treatment to make sure you are
physically comfortable and free from pain.
ASCO ANSWERS is a collection of oncologist-approved patient education materials developed by the American
Society of Clinical Oncology (ASCO) for people with cancer and their caregivers.
FOR PATIENTS
FOR CANCER PRACTICES
• Information on 120+ Cancer Types
• Downloadable Educational Resources
• Age-Specific Resources
• Medical Illustrations
• Blog Posts on Timely Topics
• Free Cancer.Net and Mobile App
Referral Cards (call 888-651-3038 or
email [email protected])
• Videos and Podcasts
• Coping and Survivorship Resources
• Information in Spanish
• An Award-Winning Mobile App for
iPhone and Android Devices
• Fact Sheets, Guides, and Booklets
on a Wide Variety of Topics
(cancer.net/estore)
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The research featured in ASCO’s Clinical Cancer Advances report is a
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investigators are funded, and the knowledge of practicing oncologists is
pooled. Together, we’re making it harder for cancer to survive.
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