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cancernsight™
June 2016
VOLUME 12, ISSUE 3
Kantar Health discusses
the pivotal clinical trials
presented at the 2016
American ASSOCIATION For
Cancer Research (AACR)
Annual Meeting
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catalysts driving
successful decisions
in life sciences
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contents
This issue of
CancerNSight™
highlights
significant
information
presented at
2016 AACR.
2016 AACR Annual Meeting
© 2016 Kantar Health
Opdivo calls CheckMate on Investigator’s Choice in Platinum-Refractory
Head and Neck Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Kantar Health’s Oncology Conference Coverage . . . . . . . . . . . . . . . . . 6
Kantar Health Oncology Thought Leadership. . . . . . . . . . . . . . . . . . . . . 7
www.kantarhealth.com
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ABOUT
THE experts
Opdivo calls CheckMate on Investigator’s Choice in PlatinumRefractory Head and Neck Cancer
by ARNOLD DUBELL AND Jay Grisolano
Senior Consultant,
Clinical & Scientific
Assessment
Patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and
neck (SCCHN) currently have few treatment options and a poor prognosis. In the first-line
setting, patients are primarily treated with Erbitux® (cetuximab, Merck KGaA/BristolMyers Squibb/Eli Lilly) plus chemotherapy and, in later lines of therapy, may be treated
with Erbitux monotherapy or a variety of other single-agent systemic therapies. Since
approval of Erbitux in combination with 5-fluorouracil and a platinum agent for first-line
use in 2011, no new targeted therapies have been approved for head and neck cancer.
The unmet need for this tumor type is further illustrated by the fact that only one-half of
first-line patients will receive second-line treatment, while even fewer patients will receive
third-line therapy or beyond.1
Jay Grisolano,
Ph.D.
Patients with head and neck cancer may soon have new, exciting options in the form of
immunotherapies, namely PD-1 inhibitors. These agents have dramatically improved
outcomes in indications such as melanoma, non-small cell lung cancer (NSCLC) and
renal cell carcinoma (RCC) and are now showing efficacy in head and neck cancer. The
first late-stage data for one agent in this class, Opdivo® (nivolumab, Bristol-Myers Squibb/
Ono Pharmaceuticals), were presented at the 2016 American Association of Cancer
Research (AACR) annual meeting, as Dr. Maura Gillison presented results from the
CheckMate-141 trial.2
Arnold DuBell,
Ph.d., m.b.a.
Director, Clincial &
Scientific Assessment
CheckMate-141 randomized (2:1) 361 patients with R/M SCCHN to treatment with Opdivo
(3) or the investigator’s choice of chemotherapy (methotrexate, docetaxel, or Erbitux).
Although most patients (45%) received only one prior line of therapy, almost 20% of
patients were treated with three or more prior lines of systemic therapy. CheckMate-141
was stopped at its interim analysis in January 2016 after crossing the defined threshold
for meeting its overall survival (OS) primary endpoint, a 30% reduction in the risk of death.
As reported at AACR, patients treated with Opdivo enjoyed a 2.4-month OS improvement
compared with patients treated in the control arm (7.5 months versus 5.1 months, HR
0.70, p=0.0101). Notably, at one year patients treated with Opdivo had twice the probability
of remaining alive than patients on the control arm (one-year OS rate: 36.0% versus
16.6%). Moreover, the OS benefit may increase as 17.4% of patients are continuing Opdivo
therapy compared with only 2.7% of patients on the control arm. The strength of this data
is further understood by comparing outcomes with another benchmark: the one-year
OS rate (36.0%) for Opdivo reported in CheckMate-141 in pretreated patients compares
favorably with data in the first-line EXTREME study,3 which reported a 40% one-year OS
rate for Erbitux in combination with a platinum agent and 5-fluorouracil.
Biomarker analysis was performed to determine the predictive value for PD-L1 positivity
(defined as staining ≥ 1% and seen in 57.3% of the total sample) and p16 status (a marker
for HPV-positivity). Although PD-L1-positive patients saw a greater benefit with Opdivo
than PD-L1-negative patients did (Table 1), PD-L1-negative patients did see a trend to
benefit with Opdivo (11% reduction in risk of death); however, the Kaplan-Meier curve
separated dramatically at the tail end and provides some hope for this subgroup. HPV
positivity, as measured through p16 positivity, was not predictive of benefit.
© 2016 Kantar Health
www.kantarhealth.com
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increased
competition means
increased options
for Head and Neck
Cancer patients.
As might be expected from this class of inhibitors, Opdivo was better tolerated than the
controls. Only 13.1% of patients reported Grade 3-4 adverse events on Opdivo compared
with 35.1% of patients on the control arm. Noteworthy primary toxicities of all grades
for Opdivo included endocrine abnormalities (7.6% versus 0.9%) and pneumonitis (2.1%
versus 0.9%).
Bristol-Myers Squibb publically stated at the time of the early trial closure that it was
in discussions with regulatory officials regarding filing. Since then, Opdivo received
Breakthrough Therapy Designation from the U.S. Food & Drug Administration (FDA) in
this indication, but an FDA filing has not yet been announced. Although Opdivo is the
first PD-1 inhibitor to demonstrate superiority in a randomized Phase III trial in head
and neck cancer, it will most likely need to immediately compete with Merck’s Keytruda®
(pembrolizumab). Merck announced in early April that the FDA granted priority review of
its application for accelerated approval of Keytruda, with a target action date of August
9, 2016. This application was based on updated results of the Phase Ib KEYNOTE-012
trial, which reported an overall response rate of 24.8%, median progression-free survival
(PFS) of 2.2 months, and median OS of 9.6 months in platinum-pretreated R/M SCCHN
patients.4,5 The Phase II KEYNOTE-055 trial (NCT02255097) will provide additional data
on the activity of Keytruda in the platinum-pretreated setting . Although the data for
KEYNOTE-055 has not been publically reported (it will be presented at ASCO 2016), it
may be included in Merck’s application for accelerated approval. It is unclear at this
point which PD-1 inhibitor might be approved first – although Keytruda has a PDUFA date
already set, Opdivo’s Breakthrough Status could accelerate its review process once filing
is complete. Once both are approved, physicians will undoubtedly try to tease out efficacy
and tolerability differences between the two agents, although generally the agents seem
to be equally effective in other solid tumors.
Immunotherapy development in head and neck cancer is not limited to later lines of
therapy. Merck has an ongoing Phase III trial for Keytruda in first-line (KEYNOTE-048,
NCT02358031), and MedImmune/AstraZeneca has an ongoing Phase III trial (KESTREL
(NCT02551159)) for its PD-L1 inhibitor, durvalumab, in combination with its CTLA-4
inhibitor, tremelimumab in the frontline setting (as well as the EAGLE trial (NCT02369874)
in relapsed/refractory patients). Opdivo might have difficulties once the frontline trials
report. If Keytruda or durvalumab gain broad utilization in frontline once approved in that
setting, it may reduce the opportunity for Opdivo utilization in later lines of therapy.
TABLE 1: Efficacy Data from CheckMate-141
Opdivo
Investigator’s Choice
N
mOS, months
N
mOS, months
HR
All patients
240
7.5
121
5.1
0.70
PD-L1 ≥ 1%
88
8.7
61
4.6
0.55
PD-L1 < 1%
73
5.7
38
5.8
0.89
p16-positive
63
9.1
29
4.4
0.56
p16-negative
50
7.5
36
5.8
0.73
Source: Gillison, Abstract CT-099, AACR 2016
© 2016 Kantar Health
www.kantarhealth.com
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As with other indications that immunotherapies have entered, increased competition
means increased options for patients. Opdivo should enjoy its well-earned spotlight
with the release of CheckMate-141 data, but Keytruda may pose a formidable threat if it
earns FDA approval ahead of Opdivo. It will be interesting to see which new options – new
immunotherapies or combinations with existing therapies – patients can look forward to
tomorrow.
References:
© 2016 Kantar Health
1.
Kantar Health, CancerMPact® Future Trends and Insights; accessed April 19, 2016.
2.
Gillison ML, Blumenschein G, Fayette J, et al.; “Nivolumab versus Investigator’s choice
(IC) for recurrent or metastatic (R/M) Head and neck squamous cell carcinoma (SCCHN):
CheckMate-141;” Proceedings of the 97th Annual Meeting of the American Association for
Cancer Research; 2016 Apr 16–20; New Orleans, Louisiana (LA): AACR; 2016. Abstract nr CT099.
3.
Vermorken J, Mesia R, Rivera F, et al.; “Platinum-based chemotherapy plus cetuximab in head
and neck cancer;” N Engl J Med, 359 (11): 1116-1127, 2008.
4.
Seiwert TY, Haddad RI, Gupta S, et al.; “Antitumor activity and safety of pembrolizumab
in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN):
Preliminary results from KEYNOTE-012 expansion cohort;” J Clin Oncol 33, 2015 (suppl; abstr
LBA6008).
5.
ChowL, Mehra R, Haddad R, et al.; “Antitumor activity of the Anti-PD-1 antibody pembrolizumab
in subgroups of patients with recurrent/metastatic head and neck squamous cell carcinoma
(R/M HNSCC): Exploratory analyses from KEYNOTE-012;” Vienna, Austria: European Cancer
Congress; 2015. Abstract 2866.
6.
Bauml J, Seiwert TY, Pfister DG, et al.; “Preliminary results from KEYNOTE-055:
Pembrolizumab after platinum and cetuximab failure in head and neck squamous cell
carcinoma (HNSCC);” J Clin Oncol 34, 2016 (suppl; abstr 6011).
www.kantarhealth.com
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Conference Coverage
What’s of greatest
interest to you
at this year’s
major oncology
meetings?
Every year, Kantar Health sends multidisciplinary teams of oncology experts to significant
oncology meetings around the world to analyze the most important clinical presentations,
satellite symposia, poster sessions and floor exhibits.
Oncology Conference Insight will continue to bring you highlights and breaking news from
the following 2016 oncology meetings:
Date
Meeting
Location
Jan. 7-9
Genitourinary Cancers Symposium 2016
San Francisco
Jan. 21-23
Gastrointestinal Cancers Symposium 2016
San Francisco
April 16-20
American Association for Cancer Research (AACR)
Annual Meeting 2016
New Orleans
June 3-7
American Society of Clinical Oncology (ASCO)
Annual Meeting 2016
Chicago
Oct. 7-11
European Cancer Congress 2015
European Society for Medical Oncology (ESMO)
European CanCer Organization (ECCO)
Copenhagen
Nov. 29 – Dec. 2
AACR-NCI-EORTC International Symposium on Molecular
Targets and Cancer Therapeutics Annual Meeting 2016
Munich
Dec. 3-6
American Society of Hematology (ASH) Annual Meeting 2016
San Diego
Dec. 6-10
CTRC-AACR San Antonio Breast Cancer Symposium (SABCS)
Annual Meeting 2016
San Antonio
Kantar Health’s Oncology Conference Insight service lets you define the scope of
surveillance at any given oncology meeting or conference. Coverage may be based on
tumor type, specific competitive compounds in development, or a particular mechanism
of drug action. We follow your lead, attending activities and events at that meeting
relevant to your interests. We report back to you, advising you of key takeaways, changes
to standards of care, competitor activities and messaging, and new and emerging targets
and compounds. We deliver our professional analysis and opinions on the implications for
your company.
© 2016 Kantar Health
www.kantarhealth.com
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thought leadership
ARTICLE: What’s in Store for ASCO 2016? Kantar Health Offers a
Preview
Tari Awipi and Stephanie Hawthorne
Tari Awipi, Ph.D.
Consultant, Oncology
Commercial
Strategies
Stephanie
Hawthorne,
Ph.D.
Vice President,
Clinical & Scientific
Assessment
The 2016 American Society of Clinical Oncology (ASCO) annual meeting is approaching,
and it promises to be packed with the latest data and trends from the world of oncology.
Kantar Health has identified nine pivotal abstracts that could have a significant impact
on patient management and generate the most discussion. The majority of new
advancements to be presented at ASCO will involve new opportunities for existing
therapeutics. Read more...
Blog POST: Kantar Health Spotlights Key Abstracts at ASCO 2016
ASCO 2016 is sure to live up to its reputation for delivering market-changing data and
trends from the world of oncology. Kantar Health spotlights four potentially noteworthy
abstracts that are likely to generate much discussion and significantly influence patient
care. Read more...
Article: Specialty Pharmacy Dynamics
Deni Deasy Boekell
Deni Deasy
Boekell
Senior Director,
Oncology Commercial
Strategies
As the specialty pharmaceutical marketplace grows, so does the specialty pharmacy
provider (SPP) market. And with the former growing at double-digit rates, while traditional
retail pharmacy is growing in low single digits, the attraction is obvious. Read more...
BLOG POST: Assessment of colorectal cancer treatment is long
overdue in Brazil
Otávio ClarK
Otávio ClarK,
Ph.D.
CEO and Team
Leader, Evidências
© 2016 Kantar Health
Assessing costs for patients in the treatment of metastatic colorectal cancer is the
objective of one study from Evidências - Kantar Health presented at the annual meeting of
the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), May
21-25. Read more...
www.kantarhealth.com
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CONTACTS
This information is intended to provide commercial organizations involved in the
development and marketing of new cancer therapeutics topical articles and features
relating to oncology. Each edition will include news and commentary about issues that
may affect a company’s development and commercialization strategies. Kantar Health
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DISCLAIMER: The discussions in this edition are published by Kantar Health and contain
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referred to in this edition and should not be relied upon as a statement of fact. Neither
Kantar Health nor any person acting on its behalf may be held responsible for the use
to which information contained in this publication may be put, or for any errors which,
despite careful preparation and checking, may appear.
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