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Oncology Grand Rounds
Cancer Immunotherapy
Nurse and Physician Investigators
Discuss New Agents, Novel Therapies
and Actual Cases from Practice
Wednesday, April 27, 2016
6:00 PM – 8:00 PM
Faculty
Marianne J Davies, DNP, ACNPBC, AOCNP-BC
Roy S Herbst, MD, PhD
Evan J Lipson, MD
Virginia J Seery, MSN, RN, ANP-BC
Moderator
Neil Love, MD
Oncology Tumor Panel Series
Recently Approved Agents
November 21, 2012 – April 26, 2016
Immunotherapy
• Nivolumab
• Pembrolizumab
• Ipilimumab
• Blinatumomab
Ovarian Cancer
• Olaparib
• Bevacizumab
Gastrointestinal Cancers
• Liposomal irinotecan (MM-398)
• TAS-102
• Ramucirumab
Lymphomas and CLL
• Belinostat
• Idelalisib
• Ibrutinib
Non-Small Cell Lung Cancer
Melanoma
• Osimertinib
• Afatinib
• Ceritinib
• Necitumumab
• Nivolumab
• Ramucirumab
• Talimogene laherparepvec
• Cobimetinib/vemurafenib
• Nivolumab
• Pembrolizumab
• Crizotinib
• Alectinib
Breast Cancer
• Palbociclib
• T-DM1
• Pertuzumab
www.fda.gov; www.centerwatch.org
Bladder Cancer
• Obinutuzumab
• Ofatumumab
• Venetoclax
• Pembrolizumab
• Dabrafenib
• Trametinib
• Ipilimumab
Recently Approved Agents
November 21, 2012 – April 26, 2016
Immunotherapy
• Nivolumab
• Pembrolizumab
• Ipilimumab
• Blinatumomab
www.fda.gov; www.centerwatch.org
Recently Approved Agents in Other Cancers
November 21, 2012 – April 26, 2016
Acute Leukemias
• Blinatumomab
Multiple Myeloma
• Ixazomib
• Daratumumab
• Panobinostat
• Elotuzumab
• Pomalidomide
Basal Cell Carcinoma
• Sonidegib
Prostate Cancer
• Radium-223
Chronic Leukemias
• Ponatinib
Thyroid Cancer
• Cabozantinib
• Lenvatinib
Liposarcoma and Leiomyosarcoma
• Trabectedin
www.fda.gov; www.centerwatch.org
Oncology Grand Rounds: Themes
• New agents and treatment strategies: Benefits and risks
• Counseling patients about side effects
– Practical implementation
• End-of-life care
• Psychosocial issues in patient care
• Supporting the supporters
• Job satisfaction and burnout in oncology professionals
• The oncology professional just entering practice
• The bond that heals
“Best Practices”
Patient Education and AE Management
• Educational sessions
– Review specific mechanisms of selected treatment
– Pre-treatment and at each office visit/encounter
• Assess patients ability to communicate symptoms
– Language barrier
– Access to phone; computer
• Provide a calendar or treatment schedule
– Follow-up visits
– Important time points
• Encourage patients to keep a treatment diary
• Provide prescription medications and encourage having medications on
hand for anticipated AEs
Ledezma, 2009, Rubin 2012.
Courtesy, Kathleen Madden, MSN, FNP, AOCNP, APHN
“Best Practices”
Patient Education and AE Management (cont.)
• Thorough physical assessment and evaluation of adverse
effects
– Baseline and at each office visit
• Educate patients to contact provider at the onset of adverse
effects or changes in condition from baseline
• At each office visit review the relevant potential adverse
effects of therapy
• Provide support for patients experiencing the unique patterns
of adverse events associated with new novel therapies
Ledezma, 2009, Rubin 2012.
Courtesy, Kathleen Madden, MSN, FNP, AOCNP, APHN
Module 1:
Biology of the Immune
System; Mechanisms of
Action of Cancer
Immunotherapies, Including
Checkpoint Inhibitors
33-Year-Old Woman with BRAF V600E-Mutant
Metastatic Melanoma (Ms Seery)
• 2012: Diagnosed with melanoma
• 2013: Metastatic disease
– Ipilimumab on a clinical trial  disease progression
• 2014: Nivolumab x 2 years
– Excellent response that continues
• Living with her very supportive significant other and
opened her own business
3/10/14
4/22/14
Disease progression – nivo started 3/17/14
6/6/14
2/10/15
Regression of pelvic lymph nodes with
no evidence of disease currently
Case discussion points (Ms Seery)
• At the point that the patient enrolled on the clinical trial
of ipilimumab versus ipilimumab/nivolumab, how did you
briefly explain immunotherapy and checkpoint inhibitors
specifically?
• What were the clinical issues that you emphasized the
most when discussing immunotherapy-related toxicity
with this patient?
Case discussion points (Ms Seery)
• What was the time course of the patient’s initial
response to immunotherapy treatment?
• What immunotherapy-related side effects, if any, did this
patient experience?
Case discussion points (Ms Seery)
• How do you think this experience has
affected the way the patient currently
views her life and her future?
What Is Immuno-Oncology?
• Immuno-oncology focuses on harnessing the tremendous
power of the human immune system to detect and destroy
cancer
• Why is the human immune system potentially the ultimate anticancer therapy?
– Specificity: virtually infinite antigen recognition
– Adaptability: based on tumor genetic and epigenetic
changes
– Memory: durable responses even after drug discontinuation
Courtesy, Evan J Lipson, MD
A Brief History of Immuno-Oncology
•
1796
First use of immunotherapy to control disease – smallpox
vaccine
•
1975
First production of monoclonal antibodies for therapeutic use
•
1986
IFN-alpha: First immuno-oncology treatment approved for
cancer (hairy cell leukemia)
•
1990
Bacillus Calmette-Guerin (BCG) (bladder cancer)
•
2010
Sipuleucel-T (prostate cancer)
•
2011
CTLA-4 inhibitor ipilimumab (metastatic melanoma)
•
2014
Blinatumomab (acute lymphoblastic leukemia)
•
2014
Anti-PD-1 monoclonal antibodies pembrolizumab and
nivolumab (unresectable or metastatic melanoma)
•
2015
Adjuvant ipilimumab (melanoma)
•
2015-16
Nivolumab, pembrolizumab (NSCLC, RCC)
A Road Map of Immunotherapy Agents in the
Cancer-Immune System Interaction
Killing of
cancer cells:
anti–PD-1,
anti–PD-L1
Resting T cell
Activated T cell
TUMOR
LYMPH
NODE
Release of
Tumor antigen
cancer cell
antigens:
chemotherapy,
radiation,
targeted
therapy
TCR
CD28
MHC
B7
Priming and
activation:
anti–CTLA-4
Dendritic cell
Cancer antigen
presentation:
vaccines
Courtesy, Julie R Brahmer, MD, MSc
Immune Checkpoint Blockade:
Mechanism of Action
T cell
Tumor
cell or
APC
(Immune checkpoints:
PD-1, PD-L1, CTLA-4)
Courtesy, Evan J Lipson, MD
Engaging the Brakes with Checkpoint Inhibitors
Checkpoint Pathways
Co-stimulatory Pathways
Courtesy, Julie R Brahmer, MD, MSc
Investigational and Approved Checkpoint Inhibitors
Anti-PD-1
Nivolumab*
Pembrolizumab**
Anti-PD-L1
Atezolizumab
Durvalumab
Avelumab
Anti-CTLA-4
Ipilimumab***
Tremelimumab
* FDA approval for: Melanoma, NSCLC, Renal cell carcinoma
** FDA approval for: Melanoma, NSCLC
*** FDA approval for: Melanoma
Module 2:
Predictors of Response to
Checkpoint Inhibitors;
Duration of Responses
64-Year-Old Man with Metastatic Adenocarcinoma
of the Lung (Ms Davies)
• 2014: Received carboplatin/pemetrexed  disease
progression
• 6/2015: Nivolumab
• 11/2015: Hypothyroidism treated with levothyroxine
• Continues treatment with excellent response
• Cross-country motorcycle trips, including high altitudes
of Colorado
• Walked his daughter down the aisle at her wedding
Case discussion points (Ms Davies)
• What are the patient’s most important current
goals?
Select Cancers Responding to Anti-PD-1/PD-L1
Checkpoint Inhibitors
• Melanoma
• Breast cancer
• Lung cancer
• Anal cancer
• Kidney cancer
• Mesothelioma
• Bladder cancer
• Lymphoma (Hodgkin lymphoma,
etc)
• Head and neck cancer
• Gastric cancer
Courtesy, Evan J Lipson, MD
• Mismatch repair deficient tumors
(colorectal cancer, etc)
Single-Agent Activity of PD-1/PD-L1 Axis Blockade
in Relapsed/Refractory Cancer
Hodgkin
Lymphoma
B and T
NHL
Batlevi et al. Nat Rev Clinic Oncol 2015;[Epub ahead of print].
Key Immunotherapy Approvals in Melanoma
Date
Agent/Regimen
Approval
3/2011
Ipilimumab
Unresectable or metastatic melanoma
9/2014
Pembrolizumab
Unresectable or metastatic melanoma
after ipilimumab or BRAF inhibitor
12/2014
Nivolumab
9/2015
10/2015
Unresectable or metastatic BRAF
V600-mutant or wild-type melanoma
Nivolumab/ipilimum
Unresectable or metastatic melanoma
ab
Ipilimumab
Adjuvant treatment for cutaneous
melanoma
Package inserts for ipilimumab, nivolumab, pembrolizumab (4/2016)
Regression of metastatic melanoma after
4 doses of PD-1 antibody
Pre-Rx
8 weeks
62-year-old man with disease progression after treatment with IL-2,
temozolomide and multiple surgical excisions
Courtesy, Evan J Lipson, MD
Immunotherapy in NSCLC
Nivolumab
•
Approved for metastatic adenocarcinoma of the lung that progresses during or
after platinum-based chemo (10/2015)
•
Approved for metastatic squamous cell NSCLC that progresses during or after
platinum-based chemo (3/2015)
Pembrolizumab
•
Approved for metastatic NSCLC whose tumors express PD-L1 by an FDAapproved test, with disease progression during or after platinum-containing
chemo (10/2015)
http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm
Immunotherapy in Renal Cell Carcinoma
Nivolumab
• Approved for metastatic renal cell carcinoma after prior
anti-angiogenic therapy (11/2015)
http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm
Immunotherapy in Urothelial Bladder Cancer
— Investigational
Pembrolizumab
•
Plimack ER et al. Pembrolizumab (MK-3475) for advanced urothelial
cancer: Updated results and biomarker analysis from KEYNOTE-012.
Proc ASCO 2015;Abstract 4502.
Atezolizumab
•
Petrylak DP et al. A phase Ia study of MPDL3280A (anti-PDL1): Updated
response and survival data in urothelial bladder cancer (UBC). Proc
ASCO 2015;Abstract 4501.
Anti-PD-L1 Atezolizumab in Metastatic Urothelial
Bladder Cancer
Patients with UBC and CR or PR as best response
• Median duration of response has not yet
been reached in either IC group
(range, 0+ to 43 mo)
1 year
• Median time to response was 62 days
- IC2/3 patients: range, 1+ to 10+ mo
- IC0/1 patients: range, 1+ to 7+ mo
• 20 of 30 responding patients had ongoing
responses at the time of data cutoff
• 10 patients have been treated for over 1
year, including 3 retreated following
protocol amendment
Days
Petrylak D et al. Proc ASCO 2015;Abstract 4501.
Treatment duration (IC2/3)
Treatment duration (IC0/1)
First CR/PR
First PD
Treatment discontinuation
Ongoing response
Anti-PD-L1 Atezolizumab in Metastatic Urothelial
Bladder Cancer
PD-L1 IHC
a
Overall
response rate
IC3 (n = 12)
67%
IC2 (n = 34)
44%
IC1 (n = 26)
19%
IC0 (n = 15)
13%
1-year
OS
50%
57%
17%
38%
**
*
*
*
**
44/80 pts (55%) with post-baseline tumor assessments experienced a reduction in tumor burden
Petrylak D et al. Proc ASCO 2015;Abstract 4501.
Immunotherapy in Hodgkin Lymphoma
Nivolumab
•
Ansell S et al. Nivolumab in patients (pts) with relapsed or refractory
classical Hodgkin lymphoma (R/R cHL): Clinical outcomes from
extended follow-up of a phase 1 study (CA209-039). Proc ASH 2015;
Abstract 583.
Pembrolizumab
•
Armand P et al. PD-1 blockade with pembrolizumab in patients with
classical Hodgkin lymphoma after brentuximab vedotin failure: Safety,
efficacy, and biomarker assessment. Proc ASH 2015;Abstract 584.
Best Response to Nivolumab in
Relapsed/Refractory Classical HL
Percent Change in Tumor Burden
25
0
SD
(13%)
PR (65%)
CR (22%)
-25
-50
-75
-100
Patients (n = 23)
On treatment, ongoing response
Off treatment without disease progressiona
Ansell S et al. Proc ASH 2015;Abstract 583.
Progressive disease, following
response or stable disease
aMaximum
clinical benefit, transplant, or toxicity
Durability of Response
100
Percent Change From Baseline
in Target Lesions/Tumor Burden
First occurrence of new lesion
On treatment, ongoing response
Off treatment without progression
50
Progressive disease, following response
or stable disease
0
–50
–100
0
6
12 18 24 30 36 42 48 54 60 66 72 78 84 90 96 102 108 114
Time Since First Treatment Date, Weeks
Ansell S et al. Proc ASH 2015;Abstract 583.
Immunotherapy in Cancer with Mismatch
Repair Deficiency
Pseudoprogression
• Not as common as we would hope.
• In CheckMate 057, seen in 16/71 patients who received treatment
beyond progression (22%), or another way to look at it — 16/292
patients who received nivolumab (5%)
Topalian S et al. NEJM 2012;366:2443-54.
Module 3:
Side Effects and
Complications of
Checkpoint Inhibitors
65-Year-Old Man with Metastatic Melanoma
(Ms Seery)
• 2013: Enrolled on a blinded clinical trial comparing
ipilimumab/nivolumab to ipilimumab alone
– Responded to treatment
– Grade 3 rash requiring corticosteroids
• Currently NED, continues treatment
• Married and a business owner
Case discussion points (Ms Seery)
• After the patient was enrolled on a clinicial trial of
ipilimumab versus ipilimumab/nivolumab, how did
his rash present? How was it managed clinically?
• How prevalent are dermatologic toxicities in
patients who are receiving checkpoint inhibitors?
What is the general time frame for onset of
dermatologic toxicities?
• What other dermatologic toxicities have you
observed in patients who are receiving
checkpoint inhibitors?
Case discussion points (Ms Seery)
• What have you observed in terms of toxicity
with combination immunotherapy (CTLA-4
antibody with anti-PD-1/PD-L1 antibody)
compared to that experienced with singleagent immunotherapy?
55-Year-Old Man with Metastatic Clear Cell
Carcinoma of the Kidney (Ms Seery)
• 2006: High-dose IL-2 for metastatic clear cell carcinoma
of the kidney  disease progression
– Sunitinib
• 2012: Nivolumab on a clinical trial
– 18 months later developed pneumonitis and received
corticosteroids
– Guillain-Barré syndrome treated with intravenous
immunoglobulin
• A husband, composer and music teacher
Case discussion points (Ms Seery)
• How does this man’s passion for music
relate to him as a person and his perspective
on his illness?
Immunotherapy Safety and Tolerability
Summary
• Immune-related AEs can involve ANY organ system
– Awareness and recognition are key to patient safety
• Inflammatory process affecting any organ system
• Safety profiles are distinct from chemotherapy
• Unique evaluation and management
Courtesy, Evan Lipson MD, David R Spigel, MD
Immunotherapy Safety and Tolerability
Summary
• Most toxicities are manageable, low-grade, reversible
– Rarely lead to treatment discontinuation
• PD-1 and PD-L1 inhibitor safety profiles appear similar
– However, combinations w/ CTLA-4 antibodies have
more severe toxicity
• Suspension of dosing and early use of steroids
maximize safety
Courtesy, Evan Lipson MD, David R Spigel, MD
Comparison of Checkpoint Inhibitors to
Standard Chemotherapy in Advanced NSCLC
• AE profiles
consistent with
previous studies
• For atezolizumab,
other immunemediated AEs (any
grade) included:
– AST increase
(4%)
– ALT increase
(4%)
– Pneumonitis
(2%)
– Colitis (1%)
– Hepatitis (1%)
Dry skin, stomatitis and nail disorder were additional AEs with ≥5% higher frequency in docetaxel.
Safety population includes patients who received any amount of either study treatment.
Data cutoff Jan 30, 2015
Spira A et al. Atezolizumab (MPDL3280A). Presented at ASCO 2015 Annual Meeting.
Immune-Related Adverse Events (irAEs)
Activation of the immune system against tumors
can result in a novel spectrum of irAEs
• May be due to cytokine
release by activated T cells
• May be unfamiliar to
clinicians
• Requires a multidisciplinary
approach
•
•
•
•
•
• Can be serious
• Requires prompt
recognition and treatment
• Requires patient and HCP
education
•
•
•
•
•
Occasional (5-20%) irAEs
Grade 3/4 Uncommon
Hypophysitis
Thyroiditis
Adrenal insufficiency
Colitis
Dermatitis
- macropapular/pruritus
Pneumonitis
Hepatitis
Pancreatitis
Arthritis
Neuropathies
Amos SM, et al. Blood. 2011;118:499‒509; 2. YERVOY immune-related adverse reactions management guide. October 2012.
Available at https://www.yervoy.co.uk/Images/6682_IrAR%20management%20guide%20731EMEA12PM014.pdf. Accessed September 2014;
3. Chin K, et al. Poster presented at ESMO 2008 (abstr. 787P).
Less Common irAEs
• Hematologic: hemolytic anemia, thrombocytopenia
• Cardiovascular: myocarditis, pericarditis, vasculitis
• Ocular: blepharitis, conjunctivitis, iritis, scleritis,
uveitis
• Renal: nephritis
• Neuro: encephalitis, myasthenia gravis
Courtesy, Evan Lipson MD
Median Time to Appearance of irAEs
Dose 1
Week
1
Dose 2
Dose 3
Dose 4
Dose 5
2
4
6
8
3
5
7
Hyperthyroid
Dose 6
9
10
11
Colitis
Dose 7
12
13
Dose 8
14
15
Hepatitis
Hyperthyroid
Pneumonitis
Villadolid J, Amin A. Transl Lung Cancer Res 2015;4(5):560-75.
Renal dysfunction
…
…
How to Evaluate Patients Experiencing Potential
irAEs
• Rule out other etiologies
– Infection
– Other drugs
– Metabolic causes
– Neoplasm
• Remember: irAEs can affect any organ system at any
time after the initiation of therapy
– Asymptomatic to severe
• Be vigilant: Early recognition, evaluation and treatment
are critical
Courtesy, Julie R Brahmer, MD, MSc
General Management of irAEs
According to Severity
Grade 1
• Supportive care ± withhold
drug
Grade 2
• Withhold drug
• Re-dose if toxicity resolved to
≤ grade 1
• Low-dose corticosteroids if
symptoms do not resolve in 1
week (prednisone 0.5 mg/kg/d)
Grade 3/4
• Discontinue drug
• High-dose corticosteroids
tapered over ≥ 1 month until
toxicity resolves to ≤ grade 1
(prednisone 1-2 mg/kg/d or
equivalent)
Courtesy, Evan Lipson MD, David R Spigel, MD
• Immunosuppressives
(eg, infliximab) may
be considered if
steroids not effective
• Standard algorithms
available for
management of irAEs
Immune-Mediated Colitis: Incidence, Signs and
Symptoms
• Incidence: 2% to 3%
• Diarrhea (loose stools) or more bowel movements than
usual
• Blood in stools or dark, tarry, sticky stools
• Severe stomach area (abdomen) pain or tenderness
Nivolumab package insert 2015
Autoimmune colitis
Colonoscopy performed on a 51-year-old man with metastatic
melanoma who developed watery diarrhea after receiving
an immune checkpoint-blocking drug
Images courtesy of Animesh Jain, MD, Johns Hopkins University School of Medicine
Pneumonitis
• Radiographs
– New or changes
Ground-glass changes
Nodular or interstitial
• Symptoms
– New or worsening
Cough, shortness of
breath
• Signs
– Decrease in oxygen
saturation
Diffuse interstitial infiltrates L > R
Courtesy, Julie R Brahmer, MD, MSc
Highly variable radiographic appearance of
pneumonitis
Courtesy, Evan J Lipson, MD
40-year-old woman, Stage IV melanoma after 4 doses of
CTLA-4 antibody; cough, SOB
Courtesy, Evan J Lipson, MD
Pneumonitis Treatment
Grade
Management
Grade 1
Radiographic changes
only
• Consider delay of I-O therapy
• Monitor for symptoms every 2-3 days
• Consider pulmonary and ID consults
Grade 2
Mild to moderate new
symptoms
•
•
•
•
•
Grade 3-4
Severe new symptoms;
new/worsening hypoxia;
life-threatening
Courtesy, Evan J Lipson, MD
•
•
•
•
Delay I-O therapy
Pulmonary and ID consults
Monitor symptoms daily, consider hospitalization
1 mg/kg/day of prednisolone IV or oral equivalent
Consider bronchoscopy, lung biopsy
Permanently discontinue I-O therapy
Hospitalize
Pulmonary and ID consults
1-2 mg/kg/day methylprednisolone IV or IV
equivalent
• Prophylactic antibiotics for opportunistic infections
• Consider bronchoscopy, lung biopsy
Immune-Mediated Endocrinopathies: Incidence,
Signs and Symptoms
•
•
•
Incidence: <1% to 8%
Endocrinopathies, including immune-mediated hypothyroidism, hypophysitis,
adrenal insufficiency, hypothyroidism, hyperthyroidism and Type 1 diabetes
mellitus have occurred
Signs and symptoms:
– Persistent headaches
– Extreme tiredness
– Weight gain or weight loss
– Dizziness or fainting
– Changes in mood or behavior
– Hair loss
– Feeling cold
– Constipation
– Increased thirst
– Change in frequency of urination
Nivolumab package insert 2015
Immune-Mediated Dermatitis/Rash: Incidence,
Signs and Symptoms
• Incidence: 6% to 7%
• Signs and symptoms:
– Rash
– Itchiness of skin
– Skin blisters
– Ulcers in mouth or other mucous membranes
Nivolumab package insert 2015
Example of Pruritic Rash
• Treated with oral or topical
diphenhydramine and oral
fexofenadine
• May require topical or oral
steroids
Courtesy, Julie R Brahmer, MD, MSc
Module 4:
Potential Autoimmune
Contraindications to
Immunotherapy; Special
Populations
49-Year-Old Woman with Multiple Sclerosis and
Metastatic Melanoma (Ms Davies)
• 2013: Hepatic metastases
– Ipilimumab followed by disease progression
• 9/2014: Pembrolizumab
– Treatment interruptions due to MS flares
– 12/2015: Stable disease on treatment with
pembrolizumab every 6 weeks
• At diagnosis, divorced with teenage children
• Anxiety regarding disease recurrence, body-image issues
related to eye enucleation, financial concerns
Case discussion points (Ms Davies)
• What are the patient’s specific concerns related to her
children? How do these concerns compare to those of
other patients in this setting?
89-Year-Old Man with Metastatic NSCLC
(Ms Davies)
• 2012: Pleural pericardial effusions: Metastatic
adenocarcinoma of the lung
• Nivolumab with complete tumor response
• Continues therapy free of disease
– Excellent quality of life and performance status
• Physical decline requiring rehab at skilled nursing facility
• Wife passed away a few years ago; currently living with
his daughter
Potential Contraindications to Checkpoint Inhibitor
Therapy
• Preexisting autoimmune disorders
- Rheumatoid arthritis
- Crohn’s disease
- Multiple sclerosis, et cetera
• Receiving systemic steroid therapy
• Receiving influenza vaccine
• Receiving live vaccines
• Immunodeficiency, HIV
Potentia
• Active infection
l
• Active TB
benefit?
• Others
Ipilimumab Therapy in Patients with Advanced Melanoma
and Preexisting Autoimmune Disorders (AiDs)
•
•
•
•
•
•
Retrospective characterization of clinical outcomes in 30 patients with
preexisting AiDs who received ipilimumab
15/30 patients (50%) experienced irAEs or flares of their underlying AiD,
which were generally manageable with standard treatment
6/30 (20%) experienced complete or partial responses to therapy
Median overall survival was 12.5 months
Ipilimumab appears to be safe and effective for many patients with
advanced melanoma and concurrent, preexisting AiDs
Patients should be monitored closely for irAEs and autoimmune flares
AiDs (n = 30)
Rheumatoid arthritis (RA)
6 (20%)
Psoriasis (5/30)
5 (17%)
Multiple sclerosis
2 (7%)
Crohn’s disease or ulcerative colitis
6 (20%)
Thyroiditis
3 (10%)
Systemic lupus erythematosus
2 (7%)
Sarcoidosis
2 (7%)
Other
7 (23%)
Johnson DB et al. JAMA Oncology 2016;[Epub ahead of print].
A Phase II Trial of Pembrolizumab for Melanoma
or NSCLC and Untreated Brain Metastases
• Systemic response rate: 45%
• Brain metastasis response rate: 45%
• Duration of response in the brain was at least 12
weeks for 4 of 5 responders
– All responses were ongoing at the time of data
analysis
Goldberg SB et al. Proc ASCO 2015;Abstract 8035.
Kluger HM et al. Proc ASCO 2015;Abstract 9009.
MRI Images Before and After Treatment with
Pembrolizumab
Before Pembrolizumab
After 4 mo Pembrolizumab
After 7 mo Pembrolizumab
After 4 infusions, the patient with mRCC experienced complete resolution of lung metastases,
stabilization of other metastases and regression of all brain metastases. This excellent response
was seen despite continued steroid use of dexamethasone 4 mg/day and is still ongoing after 7
months of treatment.
Rothemundt C et al. Ann Oncol 2016;27:544-52.
Key Questions Going Forward
• Anti-PD-1 versus anti-PD-L1?
• Ideal schedule/duration of therapy:
– 1 year, 2 years, indefinitely?
• Combination therapy? Sequencing/maintenance therapy?
• Chemotherapy/targeted therapy?
• Immunotherapy?
• Radiation therapy?