Immunotherapy Drug Shows Exceptional Response Rates in Rare Melanoma

Nearly nine out of 10 patients with a rare and aggressive form of skin cancer that couldn’t be surgically removed responded to an FDA-approved immunotherapy, according to a recent study.

The research, published in Nature Medicine, involved 27 patients with unresectable desmoplastic melanoma who received Merck’s Keytruda (pembrolizumab) intravenously every three weeks for up to two years. The objective response rate in the study was 89%, and the complete response rate, or patients whose cancer went away entirely, was 37%.

Antoni Ribas, M.D.

“The 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,” Antoni Ribas, M.D., the study’s senior author and director of the UCLA Health Jonsson Comprehensive Cancer Center's Tumor Immunology Program, said in a news release. “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.”

Desmoplastic melanoma accounts for 4% of all melanomas and typically develops in areas with extensive sun damage, such as the head and neck. Relapse is common, so the standard treatment is typically surgery and radiation. When the cancer metastasizes, surgery isn’t as effective, so new therapies are needed.

Because these tumors often accumulate many more mutations than other melanomas, they should theoretically be more recognizable by the immune system as malignant. That was the reasoning behind trying Keytruda, an immunotherapy that targets PD-1, in the study.

The trial results showed the drug had a lasting effect: after three years, 84% of patients remained alive, and 96% had not died from melanoma progression. Many patients continued to maintain their response even after discontinuing treatment. The drug also worked fast, with some patients seeing tumor reduction within two months of starting therapy.

Despite the successful outcome for some patients, others experienced higher than average toxicity and adverse events compared with patients who received Keytruda for other types of cancers. In this study, 10 patients (37%) experienced grade 3 or 4 adverse events, and nine patients (33%) discontinued treatment because of these side effects. The researchers attributed this partly to the older age and multiple comorbidities common in this specific indication.

The research is part of a clinical study, which has a separate cohort of patients whose disease could be surgically removed. That group demonstrated a 59% complete response rate, according to an abstract presented at the 2022 American Society of Clinical Oncology (ASCO).

The study was funded by the SWOG Cancer Research Network and the National Cancer Institute. Lead author Kari L. Kendra, M.D., is a medical oncologist with The Ohio State University Comprehensive Cancer Center.

Keytruda first received FDA approval in 2014 for patients with advanced melanoma. Since then, the drug has experienced remarkable expansion across cancer types. Keytruda has received more than 40 approvals for various cancer indications, including non-small cell lung cancer, head and neck cancer, Hodgkin lymphoma, gastric cancer, cervical cancer, and multiple other malignancies.

The drug works by blocking the PD-1 protein on immune cells, helping the immune system recognize and attack cancer cells more effectively. This broad applicability across cancer types has made Keytruda one of the most commercially successful immunotherapy drugs, generating billions in revenue for Merck.