Immunotherapy Helps Extend the Lives of Patients with Rare Form of Skin Cancer

Study found pembrolizumab shrank or eliminated tumors in nearly 90% of participants with desmoplastic melanoma that cannot be surgically removed.

A research team co-led by UCLA investigators has found that pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, can effectively shrink or eliminate tumors in patients with unresectable advanced desmoplastic melanoma, a rare and often aggressive form of skin cancer.

The study, published in Nature Medicine, showed that nearly 90% of participants experienced significant tumor reduction or complete disappearance after receiving pembrolizumab, an anti-PD-1 immune checkpoint inhibitor, highlighting the therapy as a promising treatment option for this difficult-to-treat cancer.

“Patients with advanced desmoplastic melanoma demonstrate a high response rate to single-agent PD-1 blockade therapy, reinforcing the use of anti-PD-1 as the preferred treatment option for this disease. It offers a less invasive, more targeted approach compared to surgery, radiation or combination immunotherapies, which can have more severe side effects,” said Dr. Antoni Ribas, the study’s senior author, a professor of medicine at the David Geffen School of Medicine at UCLA and director of the UCLA Health Jonsson Comprehensive Cancer Center’s Tumor Immunology Program.

Over the past decade, immunotherapy has transformed the outlook for people with advanced melanoma. Anti-PD-1 drugs, either alone or combined with other immune therapies like anti-CTLA-4 or anti-LAG-3, are now standard first-line treatments. While combination therapies can boost effectiveness, they often come with a higher risk of side effects.

Given these developments, earlier studies suggested that desmoplastic melanoma, a subtype that often develops in areas with years of sun damage and carries many DNA changes, making tumors more visible to the immune system, might respond particularly well to anti-PD-1 therapy alone.

Building on this insight, researchers launched a multicenter clinical trial called the SWOG S1512 trial, conducted by the SWOG Cancer Research Network and funded by the National Cancer Institute (NCI). It was designed with two separate cohorts. Cohort A included patients with resectable desmoplastic melanoma treated with pembrolizumab before surgery. This study focuses on the results from Cohort B.

Cohort B enrolled 27 patients whose desmoplastic melanoma had spread, or metastasized, and was considered to be inoperable. They received pembrolizumab infusions every three weeks for up to two years.

The team found that 37% of patients had a complete response, meaning their tumors completely disappeared. Overall, 89% of patients experienced tumor shrinkage or disappearance.

Importantly, the responses were often rapid, with some patients seeing tumor reduction within two months. Many maintained their remission long after stopping treatment. After three years, 84% of patients were still alive, and 72% showed no signs of cancer progression.

While the treatment was generally well-tolerated, many patients were older and had other health conditions, which caused some to experience side effects that led them to stop therapy early. Despite these early discontinuations, the treatment’s effectiveness did not appear to be reduced.

“Promising results from this trial show that pembrolizumab can offer durable benefit for patients with a melanoma subtype that previously had no successful treatment options, and now we know that desmoplastic melanoma is among the cancers with the highest response rates to the anti-PD-1 class of cancer immunotherapies.

This advances our understanding of exceptional responders to cancer immunotherapy, and it changes the treatment paradigm with a highly active and low toxicity treatment approach,” said Ribas, who is also director of the Parker Institute for Cancer Immunotherapy Center at UCLA and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

The study was funded by grants from SWOG, National Institutes of Health and the National Cancer Institute.

Kari Kendra, MD, PhD, a SWOG investigator and medical oncologist with The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, is the first author of the study.

Other UCLA authors include Egmidio Medina, Ignacio Baselga-Carretero, Cynthia R. Gonzalez, Ivan Perez Garcilazo, Agustin Vega-Crespo, Jia Ming Chen and Nataly Naser Al-Deen. A full list of authors can be found in the study.

Title: Anti-PD-1 therapy in unresectable desmoplastic melanoma: the phase 2 SWOG S1512 trial

Authors: Kari L. Kendra, Shay L. Bellasea, Zeynep Eroglu, Siwen Hu-Lieskovan, Katie M. Campbell, William E. Carson III, David A. Wada, Jose A. Plaza, Jeffrey A. Sosman, Gino K. In, Alexandra Ikeguchi, John Hyngstrom, Andrew S. Brohl, I. Khushalani Nikhil, Joseph Markowitz, George Negrea, Samer Kasbari, Gary C. Doolittle, Umang Swami, Toni Roberts, Boban N. Mathew, Egmidio Medina, Ignacio Baselga-Carretero, Cynthia R. Gonzalez, Ivan Perez Garcilazo, Agustin Vega-Crespo, Jia Ming Chen, Nataly Naser Al-Deen, Sapna P. Patel, Elad Sharon, James Moon, Michael C. Wu, Antoni Ribas

You can read the Full Article on Nature Medicine.

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