Release Date: April 30, 2018
Expiration Date: April 30, 2019
Media: Internet - based
Community Practice Connections™ 14th Annual International Symposium on Melanoma and Other Cutaneous Malignancies® highlights current and developing therapies for patients with melanoma and Merkel cell carcinoma, including targeted therapy and immune checkpoint inhibitors. The management of skin cancer and other cutaneous malignancies has radically changed in recent years, in both the advanced and adjuvant disease settings. These changes have been paradigm-changing and great news for your patients, but they have also created educational gaps particularly for community practitioners who face the continuous challenge of staying abreast of vital issues relevant to their clinical practices. Through clinical vignettes and short interviews addressing key questions, you will hear directly from top experts in melanoma and other cutaneous malignancies on the appropriate use and sequencing of recently approved agents, companion diagnostic tests, findings from key clinical trials, updates made to treatment guidelines and recommendations, and clinical trial availability.
Acknowledgement of Commercial Support
This activity is supported by educational grants from Array BioPharma, Inc., Foundation Medicine, Inc., Merck Sharp & Dohme Corp., NewLink Genetics, Novartis Pharmaceuticals Corporation, and Prometheus Laboratories Inc.
Table of Contents
Module 1: Current and Emerging Treatment Strategies in Cutaneous Malignancies
Module 2: Treatment Options in Advanced Melanoma and Post‒PD-1 Failure
Module 3: Unmet Needs in Melanoma (Mucosal, Ocular, and CNS Disease)
Instructions for This Activity and Receiving Credit
You will need to login 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 files” will be available for your reference.
In order to receive a CME 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 certificate upon completion of these steps.
This educational activity is directed toward medical oncologists, fellows, surgical oncologists, and radiation oncologists who treat patients with skin and other cutaneous malignancies. Dermatologists, dermatopathologists and pathologists, nurse practitioners, nurses, physician assistants, pharmacists, researchers, and other health care professionals interested in the treatment of melanoma and other cutaneous malignancies will be invited to participate.
At the conclusion of this activity, you should be better prepared to:
Discuss the latest clinical trial evidence on current and emerging treatment strategies across cutaneous malignancies, including regional, immuno-, and targeted therapies
Demonstrate the impact of multidisciplinary approaches for the identification and management of treatment-related toxicities in patients with cutaneous malignancies
Detail the evolving use of biomarkers and other methods to personalize care across treatment settings for patients with melanoma and other cutaneous malignancies
Place recent and emerging trial evidence in the context of changing treatment paradigms in order to optimally sequence therapies in the management of melanoma, basal cell carcinoma, Merkel cell carcinoma, and other cutaneous malignancies
Faculty, Staff, and Planners' Disclosures
Omid Hamid, MD
Chief, Translational Research and Immuno-Oncology
Director, Cutaneous Malignancies,
The Angeles Clinic and Research Institute
Director of Experimental Therapeutics,
Cedars Sinai Medical Care Foundation
Los Angeles, CA
Disclosure:Grant Research Support: Astra Zeneca, BMS, Celldex, Genentech, Immunocore, Incyte, Merck, Merck Serano, MedImmune, Novartis, Pfizer, Rinat, Roche; Consultant: Amgen, Novartis, Roche, BMS, Merck; Speakers Bureau: BMS, Genentech, Novartis, Amgen
Jeffrey S. Weber, MD, PhD
Laura and Isaac Perlmutter Cancer Center
Professor of Medicine
NYU Langone Medical Center
New York, NY
Disclosure: Grant Research Support: BMS, GSK, Merck, Incyte, Genentech all to Moffitt; Consultant: BMS, GSK, Merck, Incyte, Genentech, AstraZeneca, Meddivation; Shareholder: Altor, Celldex, cCAM, CytomX; Other: Named on a patent held by Moffitt that relates to a predictive marker for ipilimumab
Jason J. Luke, MD, FACP
Assistant Professor of Medicine
The University of Chicago Medicine
Disclosure: Consultant: Amgen, Array, Check-Mate, Benevir, BMS, EMD Serono, Merck (unpaid)
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/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 activity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician or nurse 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)
This first of 3 PER Pulse™ Recaps will focus on recent practice-changing results in the adjuvant setting for patients with melanoma. Below are some highlights from the meeting:
Dr Weber compared the results from the CheckMate 238 trial with the COMBI A/D trial, both presented at the 2017 European Society for Medical Oncology Congress and later published in the New England Journal of Medicine
“It looks as if early on there may be a little more benefit to the BRAF/MEK adjuvant therapy with dabrafenib/trametinib, in the BRAF-mutated stage III population, but then over time, there appears to be a plateau on the immunotherapy group and less of a plateau with the targeted therapy group.”
—Jeffrey S. Weber, MD, PhD
In the CheckMate 238 trial of 906 patients undergoing complete resection for stage IIIB, IIIC, or IV melanoma, treatment with nivolumab was compared with an active control arm of ipilimumab.1
The primary endpoint of relapse-free survival (RFS) was met:
Twelve-month rate of RFS was significantly increased in the nivolumab group compared with the ipilimumab group (HR for disease recurrence or death, 0.65; 97.56% CI, 0.51-0.83; P<.001).
Grade 3 or 4 treatment-related adverse effects were lower in the nivolumab group (14.4%) than in the ipilimumab group (45.9%).
The COMBI A/D trial of 870 patients with resected stage III melanoma with BRAF
V600E or BRAF
V600K mutations compared treatment with dabrafenib plus trametinib to placebo.2
There was a significant increase in RFS with the combination treatment, as shown in the slide below.
While it is difficult to compare results from different trials, both BRAF plus MEK inhibition or PD-1 blockade with nivolumab appear to be fairly equivalent as frontline adjuvant therapy options following resection of stage III melanoma:
Two- and 3-year RFS and overall survival curves with BRAF plus MEK seem to separate and maintain the separation over time.
RFS curves for nivolumab are still maturing but may be suggestive of a plateau that may not be achieved with BRAF plus MEK inhibition.
Nivolumab adjuvant therapy may not be as efficacious in patients with BRAF-mutated disease as it is in those with BRAF wild-type disease.
In patients with stage III, BRAF-mutated disease, toxicity of BRAF plus MEK may be higher, with more patients discontinuing treatment because of adverse effects (26% vs 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.
Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377(19):1813-1823. doi: 10.1056/NEJMoa1708539.
PER Pulse Recap (2 of 3)
This second of 3 PER Pulse™ Recaps will focus on an emerging and exciting area of cancer research, the effect of the microbiome on immunotherapy treatment.
“There is a relationship between the gut, the tumor microenvironment, and the bacteria within our intestine that can shape our immune response and even shape how patients respond to therapy.” —Jennifer A. Wargo, MD
Below are some highlights from the meeting featuring Dr Wargo:
Although immune checkpoint blockade represents a major advance in the treatment of melanoma and other cancers, durable responses are not consistently yielded among patients. Research into discovering predictive biomarkers is under way and could enhance clinicians’ capability to personalize care across treatment settings for patients with melanoma and other cutaneous malignancies.
Treatment response is affected by multiple factors, including:
Tumor genome and epigenome
Environmental factors, including the microbiome
Microbial imbalance of the gut microbiome (dysbiosis) is associated with many diseases, and there is compelling evidence emerging that the microbiome may also influence response to cancer therapy, especially treatment with immunotherapy. In a recent study by Gopalakrishnan et al,1
samples of the oral and gut (fecal) microbiome were analyzed in 112 patients with metastatic melanoma starting treatment with anti‒PD-1 therapy.
The following findings were reported:
Responders (n = 30) to anti‒PD-1 therapy had a higher diversity in their gut microbiome than did nonresponders (n = 13; P<.01).
Higher diversity of the gut microbiome was associated with improved progression-free survival in patients with melanoma on anti‒PD-1 therapy (P<.05).
Further investigation through immune profiling of responding patients with a favorable gut microbiome, as well as in germ-free mice that received fecal transplants from responding patients, showed evidence of heightened systemic and antitumor immunity. Further study is ongoing to elucidate the mechanisms and to test strategies to improve therapeutic responses in patients.
Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103. doi: 10.1126/science.aan4236.
PER Pulse Recap (3 of 3)
This third of 3 PER Pulse™ Recaps will focus on unmet needs in melanoma, including patients with central nervous system (CNS), mucosal, and ocular diseases.
A significant unmet clinical need remains for patients with noncutaneous melanoma, highlighted by the drastic differences in the survival curves between cutaneous and noncutaneous melanoma. As data begin to report out at scientific meetings, some potentially practice-changing results are beginning to emerge. Below are some highlights from the meeting featuring Dr Luke:
Dr Luke noted the exciting future potential of immunotherapy to address some of the unmet needs in patients with melanoma who have brain metastases.
“I would even postulate that in patients who have low-volume brain metastases, the use of immunotherapy should be prioritized over radiation.”
— Jason J. Luke, MD, FACP
Historically, patients with melanoma with brain metastases had survival rates of approximately 6 months. Impressive data presented at the 2017 American Society of Clinical Oncology Annual Meeting from the CheckMate 204 study1
showed that the group of patients treated with nivolumab plus ipilimumab combination therapy yielded intracranial objective response rates of 56% (95% CI, 44-68), with 19% of patients experiencing a complete response. A fair degree of concordance between the intracranial and extracranial response was demonstrated.
Differing primary molecular and immune biology are found in cutaneous versus noncutaneous melanomas:
Acral and mucosal melanomas are associated with changes in the structure of the DNA and mutation sequences of unknown etiology.
Biology underpinning different melanoma types includes MAPK dependency; however, other molecular signaling pathways are also involved:
Acral or mucosal: KIT
Uveal: GNAQ/11, PKC
Checkpoint immunotherapy, although a standard of care, may be of less value in some noncutaneous melanoma cases:
Benefit with immune checkpoint inhibitors in uveal melanoma is not clinically meaningful.
Emerging data with pembrolizumab in patients with mucosal melanoma have shown durable benefit in some patients.2
Participation in clinical trials should be prioritized for patients with noncutaneous melanoma.
Tawbi HAH, Forsyth PA, Algazi AP, et al. Efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) in patients with melanoma (MEL) metastatic to the brain: results of the phase II study CheckMate 204. J Clin Oncol. 2017;35(15; abstr 9507).
Butler M, Hamid O, Ribas A, et al. Efficacy of pembrolizumab in patients with advanced mucosal melanoma enrolled in the KEYNOTE-001, 002, and 006 studies. Paper presented at: ECCO2017 European Cancer Congress; January 2017; Amsterdam, the Netherlands.
For additional commentary about these topics and others, visit www.gotoper.com
to access more resources from the archived 14th Annual International Symposium on Melanoma and Other Cutaneous Malignancies®