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Physicians' Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Physicians' Education Resource®, LLC, designates this enduring material for a maximum of 1.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Physicians' Education Resource®, LLC, is approved by the California Board of Registered Nursing, Provider #16669, for 1.75 Contact Hours.

Acknowledgment of Commercial Support

This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP and Tesaro Inc.

2017 Year in Review: Clinical Impact of Immunotherapies in the Treatment of Cancer


Release Date: March 30, 2018
Expiration Date: March 30, 2019
Media: Internet - based

 

Activity Overview

Immunotherapy options for patients with cancer are increasing rapidly, shaping the treatment landscape for patients with a variety of different malignancies. This online activity features an expert panel of oncologists who will discuss recent advancements in the field of immunotherapy, highlighting noteworthy data presented at major society meetings in 2017. Each module will focus on a different component of immunotherapy and its growing impact in cancer care. Topics will include advancements in the understanding of immunotherapy mechanisms and tumor biology, the exploration of prognostic markers to personalize immunotherapy utilization, an analysis of key safety and efficacy data from recent clinical trials of immunotherapy, and a look ahead at ongoing immunotherapy studies for patients with cancer.

Our panel of experts will provide clinical insight into the implications of recent immunotherapy-related data, review the potential application of these data, and discuss the future direction of immunotherapy strategies for patients with cancer.

Acknowledgement of Commercial Support

This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP, and Tesaro Inc.

CME Activity Table of Contents

  • Welcome and Introductions
  • Module 1: Biology and Mechanisms of Immunotherapy Agents
  • Module 2: Personalizing Care – Evolving Evidence on Biomarkers
  • Module 3: Current Strategies and Key Study Data
  • Module 4: Emerging Combinations and Next Steps in Clinical Trials
  • Summary and Closing Remarks

Instructions for This Activity and Receiving Credit

  • You will need to log in to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review videos/content until you finish the presentation.
  • At the end of the activity, “Educational Content/Video” will be available for your reference.
  • In order to receive a CME/CE certificate, you must complete the activity.
  • Complete the Posttest and pass with a score of 70% or higher, complete the Evaluation, and then click on “Request for Credit.” You may immediately download a CME/CE certificate upon completion of these steps.


Target Audience

This educational activity is directed toward medical oncologists, surgical oncologists, radiation oncologists, and pulmonologists involved in the treatment and management of patients with cancer. Fellows, nurse practitioners, nurses, physician assistants, pharmacists, researchers, and other healthcare professionals (HCPs) interested in the treatment of cancer are also invited to participate.

Learning Objectives

At the conclusion of this activity, you should be better prepared to:

  • Evaluate the latest data regarding mechanisms of immunotherapeutic strategies as they apply to solid and liquid malignancies and emerging biomarkers guiding the optimal selection of patients
  • Review efficacy and safety data for immunotherapeutic approaches across multiple malignancies and patient types
  • Describe key clinical issues regarding the application of immune checkpoint inhibitors and summarize ongoing associated clinical trials
  • Determine the occurrence and methods to mitigate the impact of immune-related adverse events based on recent clinical trial evidence

Faculty, Staff, and Planners' Disclosures

Faculty

Naiyer A. Rizvi, MD
Professor of Medicine
Director, Thoracic Oncology
Co-Director, Cancer Immunotherapy Program
Price Chair in Clinical Translational Research
Columbia University Medical Center
New York, NY

Disclosure: Consultant: Roche, AstraZeneca, Novartis, Merck, Lilly, Bristol-Myers Squibb, Pfizer, Gritstone Oncology, ARMO Biosciences

Ezra Cohen, MD, FRCPSC, FASCO
Professor, Division of Hematology/Oncology, Department of Medicine
University of California, San Diego
Associate Director for Translational Science, Moores Cancer Center
Director, Cancer Immunotherapy, Moores Cancer Center
Co-Leader, Solid Tumor Therapeutics Program
Co-Director, Head and Neck Cancer Center of Excellence
San Diego, CA

Disclosure: Research Grants: AstraZeneca/MedImmune, Bristol-Myers Squibb, Clovis, Genentech, Johnson & Johnson, Lilly, Merck, Novartis; Consultant: Ariad, AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Clovis, Genentech, Guardant Health, Lilly, Liquid Genomics, Merck, Mirati, Novartis, Peregrine, Pfizer, Roche Diagnostics, Synta, Trovagene

Susan F. Slovin, MD, PhD
Attending Physician
Genitourinary Oncology Service
Sidney Kimmel Center for Prostate and Urologic Cancers
Memorial Sloan Kettering Cancer Center
New York, NY

Disclosure: No relevant financial relationships with commercial interests to disclose.

The staff of PER® have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER®.

PER Pulse™ Recap

Pulse Recap (1 of 3)
 
What is our current understanding of the biology and mechanisms of key immunotherapy options in the treatment of cancer?
This is an exciting time for the emergence of immunotherapy options for a variety of malignancies. Several checkpoint inhibitors have gained approval within the past year, focusing on cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand-1 (PD-L1). Key similarities and differences between CTLA-4 and PD-1 are outlined in the table below:
CTLA-4/PD-1 Similarities CTLA-4/PD-1 Differences
B7 receptor family member CTLA-4 limits T-cell responses early in immune response (lymphoid tissues); PD-1 limits T-cell responses later in peripheral tissue
Expressed by activated T cells CTLA-4 on T cells only; PD-1 on T cells and other immune cells
Reduce T-cell proliferation, glucose metabolism, cytokine production, survival CTLA-4 ligands expressed on antigen presenting cells (APCs); PD-1 expressed on APCs, other immune cells and tumor cells
CTLA-4 affects regulatory T cell (Treg) functioning; unclear role of PD-1 on Tregs
 
Some checkpoint inhibitor therapies have been shown to have varying degrees of efficacy for different tumor types. For patients with genitourinary malignancies, efficacy appears to be more pronounced for bladder cancer than renal or prostate cancer. Hypermutational status may be a factor governing treatment response, as well as the upregulation of glycolytic and aldose reductase pathways1 and the repression of T-cell mitochondrial activity.2 While checkpoint inhibitors can influence cytolytic effector functions, adoptive T-cell therapy can influence T-cell activation.
 
  • Multiple immunotherapy options have emerged in the treatment of cancer, with several checkpoint inhibitors approved in 2017, as well as chimeric-antigen receptor (CAR) T-cell therapy.
  • Not all tumor types have the same degree of response to immunotherapy, with checkpoint inhibitor approvals noted for melanoma, renal cell cancer, colorectal cancer, non—small cell lung cancer (NSCLC), head and neck cancer, Hodgkin lymphoma, hepatocellular carcinoma, and urothelial cancer.
  • For further exploration of intriguing updates on the biology and mechanisms of immunotherapy agents, the current state of biomarkers that may shape immunotherapeutic approaches, and a review of key studies in immunotherapy for patients with cancer, please go to: gotoper.com/online-cme-activities/year-in-review/2017-year-in-review-clinical-impact-of-immunotherapies-in-the-treatment-of-cancer.
 
References:
  1. Jaiswal AR, Pudakalakatti S, Dutta P, et al. Metabolic adaptations establish immunotherapy resistance in melanoma. Presented at: SITC 2017; November 8-12, 2017; National Harbor, MD. Abstract O26. higherlogicdownload.s3.amazonaws.com/SITCANCER/3bcb5ebf-803a-42fe-83b6-0773bc4eb962/UploadedImages/Annual%20Meeting%202017/SITC_2017_Abstract_Book.pdf.
  2. Menk A, Scharping N, Dunstane D, et al. 41BB costimulation enables PD-1 blockade therapy by inducing T cell mitochondrial function and biogenesis. Presented at: SITC 2017; November 8-12, 2017; National Harbor, MD. Abstract P152. 0773bc4eb962/UploadedImages/Annual%20Meeting%202017/SITC_2017_Abstract_Book.pdf.

Pulse Recap (2 of 3)
 
Which biomarkers are garnering clinical interest for guidance of immunotherapy for patients with cancer?
 
The quest for relevant biomarkers to guide the use of immunotherapy in the treatment of cancer continues to evolve. Although approvals for the treatment of melanoma have been granted without a designated biomarker, study results have revealed some subtleties with immune checkpoint combinations, as seen in the Checkmate 067 study. For patients who had a PD-L1 expression level <5%, the hazard ratio favoring the combination of nivolumab and ipilimumab was more favorable than what was seen in those who had a PD-L1 expression level ≥5%.1
In bladder cancer, multiple checkpoint inhibitors have been approved, with several approaches to PD-L1 assessment being pursued by their respective manufacturers.
In the KEYNOTE-024 study, patients with NSCLC who had a PD-L1 expression >50% had a clear benefit with the use of pembrolizumab compared with chemotherapy.2 CheckMate 026 assessed a 5% threshold, with no differences in response noted. However, tumor mutational burden (TMB) was also assessed in CheckMate 026, with a greater progression-free survival (PFS) noted for nivolumab recipients who had a high TMB. This difference was particularly pronounced for patients who had a high TMB and a PD-L1 expression level ≥50%.3,4
Response to immunotherapy has been shown to correlate with TMB for several types of malignancies.5 Mutations that are clinically relevant, such as missense mutations, need to be identified. Frameshift mutations may also be relevant.
In small cell lung cancer (SCLC), tumor PD-L1 expression is uncommon, and responses have been observed regardless of PD-L1 status. Improved biomarkers are needed to help guide immunotherapy in SCLC. TMB analysis for CheckMate 032 showed a distinct overall survival (OS) benefit for the combination of nivolumab and ipilimumab for patients with SCLC who had a high TMB.6
Plasma-based TMB assays are also gaining traction, with the noteworthy incorporation of a plasma-based panel in studies reported by Gandara and colleagues.7 Clinical testing strategies to assess microsatellite instability/mismatch repair abnormalities and response to immunotherapy are also being pursued.8
  • PD-L1 expression and TMB have been studied extensively as a means of guiding immunotherapy options for patients with cancer.
  • The type of mutation may be particularly relevant (ie, frameshift mutations) in determining degree of immunogenicity.
  • For further exploration of intriguing updates on the biology and mechanisms of immunotherapy agents, the current state of biomarkers that may shape immunotherapeutic approaches, and a review of key studies in immunotherapy for patients with cancer, please go to: gotoper.com/online-cme-activities/year-in-review/2017-year-in-review-clinical-impact-of-immunotherapies-in-the-treatment-of-cancer.
References:
  1. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Overall survival results from a phase III trial of nivolumab combined with ipilimumab in treatment-naïve patients with advanced melanoma (CheckMate 067). In: Proceedings of the American Association for Cancer Research; April 1-5, 2017; Washington, DC. Abstract CT075.
  2. Reck M, Rodriguez-Abreu D, Robinson AG, et al; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823-1833.
  3. Peters S, Creelan B, Hellmann MD, et al. Impact of tumor mutation burden on the efficacy of first-line nivolumab in stave IV or recurrent non-small cell lung cancer. In: Proceedings of the American Association for Cancer Research; April 1-5, 2017; Washington, DC. Abstract CT082.
  4. Carbone DP, Reck M, Paz-Ares L, et al; CheckMate 026 Investigators. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017;376(25):2415-2426. doi: 10.1056/NEJMoa1613493.
  5. Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 2017;377(25):2500-2501. doi: 10.1056/NEJMc1713444.
  6. Antonia SJ et al. Impact of tumor mutation burden on the efficacy of nivolumab or nivolumab + ipilimumab in small cell lung cancer: an exploratory analysis of CheckMate 032. Presented at: 18th World Conference on Lung Cancer; October 15-18, 2017; Yokohama, Japan. Abstract OA 07.03a. library.iaslc.org/conference-program?product_id=7&author=&category=&date=2017-10-16&session_type=&presentation=&keyword=&available=&page=7.
  7. Gandara DR, Kowanetz M, Mok TSK, et al. Blood-based biomarkers for cancer immunotherapy: tumor mutational burden in blood is associated with improved atezolizumab efficacy in 2L+ NSCLC (POPLAR and OAK). Ann Oncol. 2017;28(suppl 5):mdx380. academic.oup.com/annonc/article/28/suppl_5/mdx380/4109443?searchresult=1. Published September 18, 2017. Accessed April 9, 2018.
  8. Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509-2520. doi: 10.1056/NEJMoa1500596.

Pulse Recap (3 of 3)
 
What were some of the key potentially practice-changing immunotherapy studies presented at major oncology meetings in 2017?
Cohort G of the KEYNOTE-021 study evaluated the safety and efficacy of adding pembrolizumab to pemetrexed and carboplatin (PC) for patients with untreated stage III or IV nonsquamous NSCLC. This study showed significant improvement in overall response rate with the addition of pembrolizumab to PC relative to PC alone, as well as OS and PFS.1,2
The IMpower 150 study showed an improvement in PFS using a regimen of atezolizumab, bevacizumab, carboplatin, and paclitaxel for patients with stage IV or recurrent NSCLC relative to patients in the control arm, which did not receive atezolizumab.3 All subgroups appeared to benefit from the 4-drug regimen, even when stratified according to different biomarkers.3
In melanoma, adjuvant ipilimumab has been in use for several years. In a subgroup analysis of patients undergoing resection of stage IIIB, IIIC, or IV melanoma, patients treated with nivolumab had a greater 1 year recurrence-free survival rate than patients treated with ipilimumab.4
The phase III PACIFIC trial of patients with stage III locally advanced unresectable NSCLC assessed the safety and efficacy of durvalumab versus placebo following treatment with chemoradiation therapy. Patients treated with durvalumab had a significant improvement in PFS.5,6 Durvalumab was shown to have benefit across multiple subgroups of patients, with time to distant metastasis or death also showing improvement.5,6
With respect to squamous cell carcinoma of the head and neck, the CheckMate 141 study results showed significant improvement in OS for patients receiving nivolumab compared with those receiving standard-of-care (SOC) treatment.7 A similar benefit was seen for patients receiving pembrolizumab compared with SOC treatment in the KEYNOTE-040 study.8
Other key studies reported intriguing findings related to immunotherapy combination approaches, including the combination of atezolizumab and bevacizumab for renal cell carcinoma in the IMmotion150 study, epacadostat and pembrolizumab for melanoma in the ECHO-202/KEYNOTE-037 study, niraparib and pembrolizumab for platinum-resistant ovarian cancer or triple negative breast cancer in the TOPACIO study, and many others.
Several studies pertaining to safety and efficacy data related to CAR T-cell therapy for hematologic malignancies were also presented, with fascinating results.
  • Multiple studies of checkpoint inhibitors and CAR T-cell therapies, which are helping to change the immunotherapy landscape for multiple types of cancers, presented significant data in 2017
  • For further exploration of intriguing updates on the biology and mechanisms of immunotherapy agents, the current state of biomarkers that may shape immunotherapeutic approaches, and a review of key studies in immunotherapy for patients with cancer, please go to: gotoper.com/online-cme-activities/year-in-review/2017-year-in-review-clinical-impact-of-immunotherapies-in-the-treatment-of-cancer.
 
References
  1. Langer CJ, Gadgeel SM, Borghaei H, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497-1508.
  2. Borghaei H, Langer CJ, Gadgeel SM, et al. Pemetrexed-carboplatin plus pembrolizumab as first-line therapy for advanced nonsquamous NSCLC: KEYNOTE-021 cohort G update. Presented at: International Association for the Study of Lung Cancer 18th World Conference on Lung Cancer; October 2017; Yokohama, Japan. Abstract OA 17.01.
  3. Reck M, et al. ESMO IO 2017. Primary PFS and safety analyses of a randomized phase III study of carboplatin + paclitaxel +/− bevacizumab, with or without atezolizumab in 1L non-squamous metastatic NSCLC (IMpower150). Presented at: ESMO Immuno Oncology Congress 2017; December 2017; Geneva, Switzerland. Abstract LBA1_PR.
  4. Weber J, Mandala M, Del Vecchio M, et al; CheckMate 238 Collaborators. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377(19):1824-1835. doi: 10.1056/NEJMoa1709030.
  5. Paz-Ares L et al. PACIFIC: A double-blind, placebo-controlled Phase III study of durvalumab after chemoradiation therapy (CRT) in patients with Stage III, locally advanced, unresectable NSCLC. Presented at: 2017 European Society for Medical Oncology Congress (ESMO 2017); September 2017; Madrid, Spain. Abstract LBA1.
  6. Antonia SJ et al. N Engl J Med. 2017 Sep 8. [Epub ahead of print]. Article published online ahead of print.
  7. Gillison ML, Blumenschein GR, Fayette J, et al. Nivolumab vs investigator’s choice for platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): outcomes in first-line recurrent or metastatic patients and updated safety and efficacy. Presented at: ASCO 2017 Annual Meeting, June 2017; Chicago, Illinois. Abstract 6019.
  8. Cohen EEW, Harrington KJ, Le Tourneau C, et al. Pembrolizumab (pembro) vs standard of care (SOC) for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): Phase 3 KEYNOTE-040 trial. Presented at ESMO 2017 Congress; September 8-12, 2017; Madrid, Spain. Abstract LBA45_PR.








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