Many melanoma patients could avoid the risk for toxicity from combination therapies, study suggests

Data from a national clinical trial shows that a striking 89% of patients with desmoplastic melanoma responded to immunotherapy (pembrolizumab) alone, suggesting that many patients could avoid the risk for toxicity from combination therapies and achieve cancer control with this approach to treatment.

Desmoplastic melanoma is a subset of melanoma skin cancer that is caused by high levels of ultraviolet (UV) radiation damage and, therefore, a high number of tumor mutations that all contribute to aggressive disease development and growth.

Not all melanomas are the same, and they don't respond to treatments in the same degree. Identifying the best treatment strategies for these unique patients can improve outcomes, which is our continual goal. This study makes us truly question whether combination therapy is necessary for these patients, and it presents important knowledge that could help us further tailor treatment based on characteristics of the patient's unique tumor and reduce the potential for toxicity from combination therapies."

Kari Kendra, MD, PhD, study principal investigator, medical oncologist who specializes in the treatment of melanoma at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)

Dr. Kendra reports the team's findings at the American Association for Cancer Research 2023 annual meeting on Sunday, April 16 at 3:30 p.m. ET.

In this SWOG Cancer Research Network-sponsored study, researchers previously reported results on Cohort A in which recruitment of 30 patients with resectable melanoma treated with three cycles of pembrolizumab (pronounced pem-bro-LIH-zoo-mab, marketed as Keytruda) resulting in a pathologic complete response rate of 55% – meaning there was no evidence of disease after treatment. Here the researchers report the findings for Cohort B, treatment of those with unresectable disease with pembrolizumab. Twenty-seven patients with desmoplastic melanoma that could not be treated with surgery were recruited. Of the participating patients, 89% had a favorable treatment response to single-agent immunotherapy treatment with pembrolizumab and 33% had complete response.

"With responses this high with single-agent pembrolizumab, combination therapy ­­– with its increased potential for toxicity­– is not needed as first-line therapy for patients with unresectable desmoplastic melanoma," says Dr. Kendra, also a researcher with the Pelotonia Institute for Immuno-Oncology and professor at The Ohio State University College of Medicine. "Many advances in the treatment of melanoma have resulted in improvement in overall survival. There are many treatment options available. Now our focus is on how we decide the best approach for each given patient."

This study (S1512) was funded by the National Institutes of Health/National Cancer Institute through grants CA180888 and CA180819. The team also received financial support from Checkmate Pharmaceuticals, GlaxoSmithKline, Immunocore, Medspace, Inc., Merck (manufacturer of the study drug), Novartis and Varian Medical Systems, Inc.

Coauthors of the study include Shay Bellasea, Zeynep Eroglu, Siwen Hu-Lieskovan, Katie M. Campbell, William Carson III, David Wada, Jose A. Plaza, Jeffrey Sosman, Gino K. IN, Alexandra Ikeguchi, John Hyngstrom, Andres Brohl, Nikhil I. Khushalani, Joseph Markowitz, George Negrea, Samer Kasbari, Gary C. Doolittle, Umang Swami, Toni Roberts, Sapna P. Patel, Elad Sharon, James Moon, Michael C. Wu, Antoni Ribas.