Study shows patients with advanced MCC treated with the experimental immunotherapy drug had longer responses than is typical for standard chemotherapy.
In a phase 2 clinical trial of the immunotherapy drug pembrolizumab as a first-line systemic therapy for advanced Merkel cell carcinoma, or MCC - a rare, aggressive type of skin cancer - the clinical response rate was similar to that typically seen with standard chemotherapy, but the duration of the response appeared to be markedly longer. There are currently no therapies that have been approved by the U.S. Food and Drug Administration for this cancer.
Multispectral immunofluorescence shows the interface between Merkel cell tumor cells (orange) and host immune cells (yellow marks CD8+ lymphocytes, red marks CD68+ macrophages). Cell-surface PD-L1 expression (green) is observed on macrophages, lymphocytes and tumor cells, adjacent to PD-1 expression (white) on lymphocytes.
Credit: Courtesy of Janis Taube, Johns Hopkins.
An objective response was observed in 56 percent of patients (14 of 25) who received pembrozilumab, and 12 of the initial 14 responses (86 percent) were ongoing at the latest follow-up in the multicenter study.
"Merkel cell carcinoma often responds to chemotherapy, but the responses are transient. Prior studies have shown that most patient's tumors have progressed by three months from starting chemotherapy, and over 90 percent of patients develop progressive disease within 10 months. In the pembrolizumab trial, 86 percent of patients who responded are still experiencing excellent disease control more than six months after starting therapy," said Dr. Paul Nghiem, affiliate investigator of the Clinical Research Division at Fred Hutchinson Cancer Research Center in Seattle, and professor of medicine, Division of Dermatology at the University of Washington School of Medicine.
This study was presented on April 19 at the American Association for Cancer Research Annual Meeting 2016 and simultaneously published in The New England Journal of Medicine.
MCC is 35 times less common than melanoma, but on average, it is about three times more likely to be deadly. About 2,000 new cases are diagnosed in the U.S. each year.
A virus that is often present on normal skin -- the Merkel cell polyomavirus -- plays a role in the development of about 80 percent of MCC cases; others result from exposure to ultraviolet sunlight. Pembrolizumab produced a durable response in patients whose MCC had been caused by the virus or by sunlight. It acts by removing the "brakes" present on tumor-specific immune cells called T cells, thereby allowing the T cells to kill the cancer cells.
Nghiem said the researchers believe the immune system is likely "seeing" different targets in the virus-positive and the virus-negative patients. In virus-positive tumors, the immune system may readily detect and target viral proteins. In contrast, virus-negative tumors have large numbers of mutations caused by sunlight that can change normal proteins in cells. With these proteins no longer appearing as "self," the immune system can see and attack the tumors.