Release Date: February 28, 2018
Expiration Date: February 28, 2019
Media: Internet - based
Community Practice Connections™: 2nd Annual International Congress on Immunotherapies in Cancer™: Focus on Practice-Changing Application features case-based discussion of the application of immune-based therapies in several tumor types. Interactive clinical vignettes are followed by short video interviews with leading oncology experts and short summaries of clinical data related to these clinical settings. The video interviews address decision points in the clinical vignettes, as well as questions commonly faced in the community oncology practice setting by physicians using immunotherapy.
Acknowledgement of Commercial Support
This activity is supported by educational grants from AstraZeneca, Merck Sharp & Dohme Corp., and Novartis Pharmaceuticals Corporation.
CME/CE Activity Table of Contents
Module 1. Acute Lymphoblastic Leukemia
Module 2. Melanoma
Module 3. Immune-Related Adverse Events
Module 4. Renal Cell Carcinoma
Module 5. Non–Small Cell Lung Cancer
Instructions for This Activity and Receiving Credit
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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 files” will be available for your reference.
In order to receive a CME/CE certificate, participants 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. Participants may immediately download a CME/CE certificate upon completion of these steps.
This educational program is directed toward oncologists, nurses, and pharmacists. Participants will be primarily those whose practice requires mastery and a critical understanding of the fundamental principles, pivotal published studies, and emerging information on the immunotherapies and their evolving roles in the treatment of cancer.
At the conclusion of this activity, you should be better prepared to:
Explain current and evolving mechanistic approaches regarding how the immune system can be targeted in the treatment of cancer
Evaluate clinical trial findings on immuno-oncology strategies, and how they can be practically applied to the management of cancer in multiple lines of care
Discuss emerging methods to personalize care via the use of biomarkers and other methods to individualize the use of immuno-oncology strategies
Describe how common and uncommon adverse events associated with the use of immuno-oncology strategies can be proactively mitigated and managed
Detail important remaining clinical questions in the field, and highly anticipated ongoing clinical trials that are evaluating emerging immuno-oncology strategies
Faculty, Staff, and Planners' Disclosures
Antoni Ribas, MD, PhD
Professor of Medicine
Professor of Surgery
Professor of Molecular & Medical Pharmacology
David Geffen School of Medicine
Director, Tumor Immunology Program, Jonsson Comprehensive Cancer Center
University of California, Los Angeles
Chair, Melanoma Committee at SWOG
Los Angeles, CA
Disclosure: Consultant: Merck, Novartis, Roche; Shareholder: Abraxis, CytomX, Compugen, Five Prime Therapeutics, Kite Pharma
David F. McDermott, MD
Leader, Dana-Farber Harvard Cancer Institute
Kidney Cancer Program
Director, Biologic Therapy and Cutaneous Oncology Programs
Beth Israel Deaconess Medical Center
Associate Professor of Medicine
Harvard Medical School
Disclosure: Grant/Research Support: Prometheus Laboratories; Consultant: Bristol-Myers Squibb, Pfizer, Merck, Novartis, Eisai, Exelixis, Array BioPharma, Genentech
David L. Porter, MD
Jodi Fisher Horowitz Professor in Leukemia Care Excellence
Director, Blood and Marrow Transplantation
Hospital of the University of Pennsylvania
Perelman Center for Advanced Medicine
Disclosure: Grant/Research Support: Novartis Research Support; Consultant: Novartis, Kite Pharma, Servier (advisory board); Shareholder: Roche
Naiyer A. Rizvi, MD
Professor of Medicine
Director, Thoracic Oncology
Co-Director, Cancer Immunotherapy Program
Price Chair, Clinical Translational Research
Columbia University Medical Center
New York, NY
Disclosure: Consultant: Merck, Roche, Bristol-Myers Squibb, AstraZeneca, ARMO BioSciences; Shareholder: Gritstone Oncology
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/CE activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME/CE 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/CE 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/CE 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™
PER Pulse Recap (1 of 3)
Insight from David L. Porter, MD– PER Pulse™ Recap:
Community Practice Connections™: 2nd Annual International Congress on Immunotherapies in Cancer™: Focus on Practice-Changing Application
The online continuing medical education (CME) activity, Community Practice Connections™: 2nd Annual International Congress on Immunotherapies in Cancer™: Focus on Practice-Changing Application
, features case-based discussion of the application of immune-based therapies in several tumor types. Program Chair Antoni Ribas, MD, PhD, joined by expert faculty David F. McDermott, MD, David L. Porter, MD, and Naiyer A. Rizvi, MD, provide perspectives on 4 clinical vignettes in patients with acute lymphoblastic lymphoma (ALL), melanoma, renal cell carcinoma (RCC), and non-small cell lung cancer (NSCLC). You will discover how the expert faculty members approach treatment decision points, as well as some of the key challenges and questions that community physicians face when treating patients with immunotherapy.
This first of 3 PER Pulse™ Recaps for the activity will focus the use of CAR T cells in young patients with highly refractory ALL. Below are some highlights from the activity featuring Dr. Porter:
In August 2017, tisagenlecleucel, a CD19-targeting CAR T-cell construct, was approved by the US Food and Drug Administration (FDA) for patients age ≤25 years with relapsed/refractory B-cell precursor ALL (second relapse or later), based on the phase II ELIANA trial enrolling 92 patients.1,2
The primary endpoint of the trial was overall response rate (ORR), that is, the rate of complete response (CR) or a CR with incomplete blood count recovery (CRi) within 3 months.
Patients in the trial had received a median of 3 prior therapies (range, 1-8 therapies). In an analysis of 75 patients with a median of ≥3 months of follow-up (median, 13.1 months), the ORR was 81% (Table
), including a CR in 60% of patients. All 61 patients achieving a CR/CRi also achieved negativity for minimal residual disease (MRD). In these patients, the median duration of response was not reached at the time of reporting; the relapse-free survival rate at 12 months was 59%. The 12-month overall survival (OS) rate in the 75 patients evaluated was 76%. Grade 3/4 cytokine release syndrome was reported in 35 patients (47%), and 10 patients (13%) experienced grade 3 neurotoxicity; no grade 4 neurotoxicity was reported.
“In a young patient, I believe CAR T cells would be a very, very effective therapy. The FDA recently just approved CAR T cells for patients up to and through age 25 with relapsed-refractory ALL, so it’s now available outside of clinical trials for general clinical use.”
— David L. Porter, MD
FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome [press release]. Silver Spring, MD: US Food and Drug Administration. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm574154.htm. Accessed September 5, 2018.
Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439-448. https://doi.org/10.1056/NEJMoa1709866.
PER Pulse Recap (2 of 3)
This second of 3 PER Pulse™ Recaps for the activity will focus on the use of immunotherapy in stage III and IV NSCLC. Below are some highlights from the meeting featuring Dr. Rizvi:
“With IMpower150, I think there are certain aspects of that which are really helpful to patients. We know that patients with liver metastases, for example, respond less well to PD-1 therapy. For the subgroup of patients with liver metastases in IMpower150, it was encouraging to see those patients doing really well.”
— Naiyer A. Rizvi, MD
For a patient with stage III NSCLC who achieved a partial response following concurrent chemoradiation therapy (CRT), expert recommendation is consolidation therapy with durvalumab, which is a category 2A recommendation in national guidelines.1
For stage III NSCLC, the use of consolidation durvalumab is based on the initial results of the phase III PACIFIC trial.2
This study compared durvalumab to placebo in patients with unresectable, stage III NSCLC who had achieved at least stable disease following concurrent CRT. Progression-free survival (PFS), one of the coprimary endpoints, was superior in the durvalumab arm (16.8 months vs 5.6 months; hazard ratio [HR], 0.52; P
<.001). A significant benefit was also seen with durvalumab in terms of disease-free survival (23.2 months vs 14.6 months; HR, 0.52; P
<.001) and ORR (28% vs 16%; P
<.001). In May 2018, it was announced that the coprimary endpoint of OS was also met in the durvalumab arm.3
The incidence of grade 3/4 adverse events (AEs) was similar between the 2 arms, with 3% of the patients in each arm experiencing grade 3/4 pneumonitis or radiation pneumonitis.
For patients with stage IV lung adenocarcinoma, with no detected oncogenic drivers and a low PD-L1 expression level, expert opinion is that an immunotherapy/chemotherapy combination is a therapeutic option.
KEYNOTE-021 and KEYNOTE-189 Trials
In May 2017, the combination of pembrolizumab and carboplatin/pemetrexed received accelerated approval from the FDA based on the randomized, phase II KEYNOTE-021 trial.4
The primary endpoint of ORR was significantly higher with pembrolizumab/chemotherapy compared with chemotherapy alone (57% vs 32%; P
=.0029). Median OS was also higher in the pembrolizumab-containing arm (median not reached vs 20.9 months; HR, 0.59; P
The phase III KEYNOTE-189 trial6
demonstrated significantly longer OS and PFS in patients with previously untreated nonsquamous NSCLC, without EGFR
mutations, who were treated with pembrolizumab plus standard chemotherapy (pemetrexed plus platinum-based drug) compared with chemotherapy alone.
Initial results from a separate phase III trial of immunotherapy plus chemotherapy, IMpower150,7
were reported in December 2017. This trial randomized patients to atezolizumab/chemotherapy, atezolizumab combined with bevacizumab/chemotherapy, or bevacizumab/chemotherapy; the chemotherapy backbone was carboplatin/paclitaxel. Evaluation of the coprimary endpoint of PFS showed superior efficacy with atezolizumab combined with bevacizumab/chemotherapy compared with bevacizumab/chemotherapy alone (8.3 months vs 6.8 months; HR, 0.62; P
<.0001). The 12-month PFS rates were 37% and 18%, respectively. The median OS was also superior in the atezolizumab-containing arm (19.2 months vs 14.7 months; HR, 0.78; P
Based on the results of the IMpower150 trial, the FDA granted priority review for atezolizumab in combination with bevacizumab, carboplatin, and paclitaxel for the first-line treatment of patients with metastatic, nonsquamous NSCLC.
NCCN Clinical Practice Guidelines in Oncology. Non–small cell lung cancer, version 6.2018. National Comprehensive Cancer Network website. nccn.org/professionals/physician_gls/pdf/nscl.pdf. Published August 17, 2018. Accessed September 5, 2018.
Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377:1919-1929. doi: 10.1056/NEJMoa1709937.
[Durvalumab] significantly improves overall survival in the Phase III PACIFIC trial for unresectable Stage III non-small cell lung cancer [press release]. AstraZeneca; May 25, 2018. https://www.astrazeneca.com/media-centre/press-releases/2018/imfinzi-significantly-improves-overall-survival-in-the-phase-iii-pacific-trial-for-unresectable-stage-iii-non-small-cell-lung-cancer-25052018.html. Accessed September 5, 2018.
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;17:1497-1508. doi: 10.1016/S1470-2045(16)30498-3.
Borghaei H, Langer CJ, Gadgeel S, et al. Updated results from KEYNOTE-021 cohort G: a randomized, phase 2 study of pemetrexed and carboplatin (PC) with or without pembrolizumab (pembro) as first-line therapy for advanced nonsquamous NSCLC. Presented at the 2017 Annual Meeting of the European Society for Medical Oncology; September 8-12, 2017; Madrid, Spain. Abstract LBA49.
Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378:2078-2092. doi: 10.1056/NEJMoa1801005.
Reck M, Socinski MA, Cappuzzo F, et al. 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 the 2017 ESMO Immuno Oncology Congress; December 7-10, 2017; Geneva, Switzerland. Abstract LBA1_PR.
Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med. 2018;378(24):2288-2301. DOI: 10.1056/NEJMoa1716948.
PER Pulse Recap (3 of 3)
This third of 3 PER Pulse™ Recaps for the activity will examine the use of immunotherapy for patients with genitourinary malignancies, with a focus on RCC. Below are some highlights from the meeting featuring Dr. McDermott:
“In the CheckMate 214 trial, the primary endpoint was focused on the outcomes in the intermediate- and poor-prognostic-risk groups. In that group, there were clear benefits in both response rate, progression-free survival, and overall survival. All the important endpoints for efficacy for the combination of nivolumab and ipilimumab.”
— David F. McDermott, MD
CheckMate 214 Trial
The CheckMate 214 trial1
randomized approximately 1100 patients; approximately three-quarters had intermediate- or poor-risk disease by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria, whereas the remainder had favorable-risk disease. In patients with intermediate-/poor-risk disease, a significant improvement in PFS, OS, and ORR was observed with nivolumab/ipilimumab compared with sunitinib (Table 1
). However, in the intent-to-treat (ITT) cohort, there was no difference between the treatment arms, and in patients with favorable-risk disease, the comparator sunitinib arm actually yielded a favorable PFS. The AE profile favored the nivolumab/ipilimumab arm, particularly in terms of grade ≥3 hypertension and palmar-plantar erythrodysesthesia (PPE) (Table 2
Based on these results, nivolumab/ipilimumab was approved by the FDA in April 2018 for patients with previously untreated advanced RCC and intermediate-/poor-risk disease.2
The IMmotion151 trial3
enrolled approximately 915 patients, of whom approximately 80% had intermediate-/poor-risk disease, with the remaining 20% having favorable-risk disease. The coprimary endpoint of investigator-assessed PFS in patients with PD-L1–positive disease was met, with significant improvement seen in the atezolizumab/bevacizumab arm compared with sunitinib (Table 3
). There appeared to be a trend toward improved PFS with atezolizumab/bevacizumab in the different IMDC risk groups. Independent assessment of PFS in patients with PD-L1–positive disease, however, did not show a significant benefit with atezolizumab/bevacizumab (hazard ratio, 0.93), and this discrepancy is under investigation. At the time of presentation, OS data were not mature, although a favorable trend was observed with atezolizumab/bevacizumab. Selected grade 3/4 AEs (Table 4
) show that the rate of hypertension was similar between the 2 arms; however, patients in the atezolizumab/bevacizumab arm experienced a lower incidence of fatigue, diarrhea, and PPE.
Change in Prescribing Information: Addition of Biomarker-Restricted Use of Immunotherapy in Bladder Cancer
The use of single-agent immunotherapy (pembrolizumab or atezolizumab) as first-line therapy in patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-based therapy has been restricted to patients with PD-L1–positive disease, as measured by an FDA-approved test.4
There is no PD-L1–based restriction for patients who are not eligible for any platinum-based chemotherapy, however. This change is based on data from 2 trials, KEYNOTE-361 and IMvigor130, which showed inferior survival with single-agent immunotherapy compared with chemotherapy-containing regimens. Details on PD-L1 expression cutoffs have been included in the prescribing information.
Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214: Efficacy and safety of nivolumab + ipilimumab (N+I) v sunitinib (S) for treatment-naïve advanced or metastatic renal cell carcinoma (mRCC), including IMDC risk and PD-L1 expression subgroups. Presented at the 2017 Annual Meeting of the European Society for Medical Oncology; September 8-12, 2017; Madrid, Spain. Abstract LBA5.
FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma [press release]. Silver Spring, MD: US Food and Drug Administration. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm604685.htm.. Accessed September 5, 2018.
Motzer RJ, Powles T, Atkins MB, et al. IMmotion151: A Randomized Phase III Study of Atezolizumab Plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma (mRCC). Presented at the 2018 Genitourinary Cancers Symposium; February 8-10, 2018; San Francisco, CA. Abstract 578.
FDA alerts health care professionals and oncology clinical investigators about an efficacy issue identified in clinical trials for some patients taking Keytruda (pembrolizumab) or Tecentriq (atezolizumab) as monotherapy to treat urothelial cancer with low expression of PD-L1 [press release]. Silver Spring, MD: US Food and Drug Administration; August 16, 2018. https://www.fda.gov/Drugs/DrugSafety/ucm608075.htm. Accessed September 5, 2018.
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