Melanoma is an aggressive skin cancer with historically limited treatment options. Approximately 50% of melanomas harbor BRAF V600 mutations. This report describes a 32-year-old man with metastatic BRAF V600-mutant melanoma who presented with cardiac involvement. Recently developed treatment options for patients with BRAF-mutant melanoma include BRAF inhibitors (vemurafenib, dabrafenib), MEK inhibitors (trametinib), and immune-based therapeutics (interleukin-2 or ipilimumab), but the most effective strategy for first-line therapy is heavily debated. Opinions vary for treatment selection, but the general consensus recommends immune-based therapies initially for asymptomatic patients with low-volume disease, and BRAF inhibitors for those with highly symptomatic or rapidly progressing disease. In this case, melanoma with cardiac involvement, although clinically uncommon, presents challenging management decisions.
Douglas B. Johnson and Jeffrey A. Sosman
Douglas B. Johnson, Riyue Bao, Kristin K. Ancell, Anthony B. Daniels, Deborah Wallace, Jeffrey A. Sosman and Jason J. Luke
Background: Uveal melanoma (UM) is an uncommon melanoma subtype with poor prognosis. Agents that have transformed the management of cutaneous melanoma have made minimal inroads in UM. Methods: We conducted a single-arm phase II study of pembrolizumab in patients with metastatic UM and performed bioinformatics analyses of publicly available datasets to characterize the activity of anti–PD-1 in this setting and to understand the mutational and immunologic profile of this disease. Results: A total of 5 patients received pembrolizumab in this study. Median overall survival was not reached, and median progression-free survival was 11.0 months. One patient experienced a complete response after one dose and 2 others experienced prolonged stable disease (20% response rate, 60% clinical benefit rate); 2 additional patients had rapidly progressing disease. Notably, the patients who benefited had either no liver metastases or small-volume disease, whereas patients with rapidly progressing disease had bulky liver involvement. We performed a bioinformatics analysis of The Cancer Genome Atlas for UM and confirmed a low mutation burden and low rates of T-cell inflammation. Note that the lack of T-cell inflammation strongly correlated with MYC pathway overexpression. Conclusions: Anti–PD-1–based therapy may cause clinical benefit in metastatic UM, seemingly more often in patients without bulky liver metastases. Lack of mutation burden and T-cell infiltration and MYC overexpression may be factors limiting therapeutic responses.
ClinicalTrials.gov identifier: NCT02359851
Daniel G. Coit, John A. Thompson, Alain Algazi, Robert Andtbacka, Christopher K. Bichakjian, William E. Carson III, Gregory A. Daniels, Dominick DiMaio, Ryan C. Fields, Martin D. Fleming, Brian Gastman, Rene Gonzalez, Valerie Guild, Douglas Johnson, Richard W. Joseph, Julie R. Lange, Mary C. Martini, Miguel A. Materin, Anthony J. Olszanski, Patrick Ott, Aparna Priyanath Gupta, Merrick I. Ross, April K. Salama, Joseph Skitzki, Susan M. Swetter, Kenneth K. Tanabe, Javier F. Torres-Roca, Vijay Trisal, Marshall M. Urist, Nicole McMillian and Anita Engh
The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.
David S. Ettinger, Wallace Akerley, Gerold Bepler, Matthew G. Blum, Andrew Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Todd L. Demmy, Apar Kishor P. Ganti, Ramaswamy Govindan, Frederic W. Grannis Jr., Thierry Jahan, Mohammad Jahanzeb, David H. Johnson, Anne Kessinger, Ritsuko Komaki, Feng-Ming Kong, Mark G. Kris, Lee M. Krug, Quynh-Thu Le, Inga T. Lennes, Renato Martins, Janis O'Malley, Raymond U. Osarogiagbon, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, George R. Simon, Scott J. Swanson, Douglas E. Wood and Stephen C. Yang
Daniel G. Coit, John A. Thompson, Mark R. Albertini, Christopher Barker, William E. Carson III, Carlo Contreras, Gregory A. Daniels, Dominick DiMaio, Ryan C. Fields, Martin D. Fleming, Morganna Freeman, Anjela Galan, Brian Gastman, Valerie Guild, Douglas Johnson, Richard W. Joseph, Julie R. Lange, Sameer Nath, Anthony J. Olszanski, Patrick Ott, Aparna Priyanath Gupta, Merrick I. Ross, April K. Salama, Joseph Skitzki, Jeffrey Sosman, Susan M. Swetter, Kenneth K. Tanabe, Evan Wuthrick, Nicole R. McMillian and Anita M. Engh
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.