Based on results from phase 2 clinical trials investigating immune checkpoint inhibitor, treatment for Merkel cell carcinoma (MCC) may be on the brink of a paradigm change, said Isaac Brownell, M.D., Ph.D., at the 16th World Congress on Cancers of the Skin in Vienna, Austria.
Avelumab (EMD Serono), an investigational anti-programmed death ligand-1 (anti-PD-L1) monoclonal antibody, was found to well-tolerated and effective in patients with chemotherapy-resistant metastatic MCC, providing rapid and durable responses.1 Similarly, the PD-1 inhibitor pembrolizumab (Keytruda, Merck) demonstrated therapeutic benefit as a first-line treatment for metastatic MCC.2
The FDA granted avelumab breakthrough therapy, fast-track, and orphan drug designations in MCC and is reviewing the biologics license application for treatment of chemotherapy-resistant metastatic MCC. Meanwhile, follow-up is continuing in the phase 2 studies of avelumab and pembrolizumab and another phase 2 trial is underway investigating avelumab as first-line therapy for patients with metastatic MCC.
“MCC is a rare and aggressive skin cancer for which the prognosis has been very poor in patients with advanced disease. Once metastasis occurs, median survival is only about 9 months as progression tends to occur within a few months after starting conventional treatment with cytotoxic chemotherapy,” according to Dr. Brownell, Investigator, Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
“Now, it appears we can offer more hope to these patients,” he says
Interest in treating MCC with immune checkpoint inhibitors stems for growing evidence that the tumor is highly regulated by the immune system.
“The immunocompromised population has a much higher incidence of MCC and a worse prognosis. Tumors in a small percentage of patients would spontaneously regress, and the presence of CD8+ tumor infiltrating lymphocytes conferred an improved prognosis,” Dr. Brownell explains.
“All of these findings suggested that immunotherapy might be a good strategy for treating MCC, and the advent of immune checkpoint inhibitors made it a more accessible approach,” he says.
In particular, there was interest in agents blocking the PD-1 immune inhibitory pathway based on the finding of high expression of PD-L1 on MCC tumors and of PD-1 by Merkel-cell polyomavirus-specific T cells.
“Merkel cell polyomavirus is the seventh identified human oncovirus and the first polyomavirus that has been linked to a human malignancy,” Dr. Brownell says.