Checkpoint Inhibitor Shows Promise in MCC
Advanced Merkel cell carcinoma patients who received KEYTRUDA® (pembrolizumab) showed more durable responses than what is typically seen with standard chemotherapy, according to a study presented at the American Association for Cancer Research Annual Meeting 2016 in New Orleans and simultaneously published in The New England Journal of Medicine.
In a phase 2 clinical trial of the PD-1 blocker pembrolizumab as a first-line systemic therapy for advanced Merkel cell carcinoma (MCC), the clinical response rate was similar to that typically seen with standard chemotherapy, but the duration of the response appeared to be markedly longer, the study showed.
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. There are currently no therapies that have been approved by the U.S. for Food and Drug Administration (FDA) for MCC. Merck's pembrolizumab has breakthrough status from the FDA for advanced melanoma, non-small cell lung cancer, colorectal cancer and classical Hodgkin Lymphoma.
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,” says study author Paul Nghiem, MD, PhD, 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.
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 T cells, thereby allowing the T cells to kill the cancer cells.
The immune system is likely “seeing” different targets in the virus-positive and the virus-negative patients, the researchers explain. 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.
The study was supported by grants from the National Cancer Institute and involved the NCI’s Cancer Therapy Evaluation Program and the Cancer Immunotherapy Trials Network. Dr. Nghiem, first and co-corresponding author, is a consultant for EMD Serono Inc. and receives funding from Bristol-Myers Squibb to perform biomarker studies in MCC clinical trials.
“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.
PHOTO: 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.