Is Immunotherapy More Effective than Chemotherapy for Skin Cancer?

Those with a rare, aggressive form of skin cancer known as Merkel cell carcinoma have shown better responses and longer survival than expected with an immunotherapy, pembrolizumab (Keytruda), than with traditional forms of chemotherapy.

The study, which included investigators from the Bloomberg-Kimmel Institute, Fred Hutchinson Cancer Research Center in Seattle, and 11 other US medical centers, is the longest observation to date of patients with Merkel cell carcinoma treated with any first-line anti-PD-1 immunotherapy.

Within the total of 50 patients in the study with various stages of Merkel cell carcinoma, more than 56% of the patients had long-lasting responses to the treatment. Twelve percent of those positively affected experienced a complete disappearance of their tumors, and approximately 70% of patients in the study were alive 2 years after starting treatment.

The findings, published in the Journal of Clinical Oncology, reaffirmed the recent FDA approval of pembrolizumab as a first-line treatment for adult and pediatric patients with recurrent locally advanced or metastatic Markel cell carcinoma.

The National Institutes of Health classifies Merkel cell carcinoma as an orphan disease, as it is diagnosed in fewer than 2000 people annually in the United States. It typically occurs in those above the age of 50 years or those who have suppressed immune systems. Approximately 80% of Merkel cell carcinomas are caused by a virus called the Merkel cell polyomavirus. The remaining cases are attributed to ultraviolet light exposure, having fair skin, and other factors.

In the study, treatment with pembrolizumab achieved positive results against both virus-positive and virus-negative Merkel cell carcinomas (the appearance or lack thereof of the Merkel cell polyomavirus) resulting in high response rates and durable progression-free survival in both subtypes. The findings also showed that tumors expressing a PD-1-related protein called PD-L1 tended to respond longer to treatment, although patients whose tumors did not express PD-L1 also responded.

Pembrolizumab works against Merkel cell carcinoma by blocking PD-1, a molecule on the surface of immune cells that regulates immune responses, turning them on and off. Cancer cells often manipulate PD-1 to send a "stop" signal to the immune system. Blocking that signal with a checkpoint inhibitor, such as pembrolizumab, initiates a "go" signal, sending immune cells to attack cancer cells. A protein on the surface of cancer cells, PD-L1, is one mechanism cancer cells use to manipulate PD-1 and disrupt the immune response.

Patients in the study received pembrolizumab intravenously every 3 weeks for up to 2 years. During this time, the status of their cancer was monitored periodically with imaging scans. Overall, most patients tolerated the treatment well; however, 28% of patients experienced serious adverse effects, including one treatment-associated death, according to the study authors.