Patients with metastatic Merkel cell carcinoma treated with pembrolizumab (Keytruda, Merck) as a first-line therapy had durable responses in a phase II clinical trial.
Patients with metastatic Merkel cell carcinoma (MCC) treated with pembrolizumab (Keytruda, Merck) as a first-line therapy had durable responses in a phase II clinical trial that lasted almost three times as long as responses to conventional chemotherapy.
These results were presented at a presscast at the American Association of Cancer Research (AACR) Annual Meeting, held April 16-20, 2016, in New Orleans. The study is also published in The New England Journal of Medicine.
The responses were in patients who had virus-driven MCC as well as MCC due to exposure to ultraviolet (UV) light and/or other unknown factors.
The objective response rate was 56% among 25 patients who could be evaluated, which was similar to the response rate seen when patients with MCC are treated with chemotherapy. Twelve of the 14 responding patients continued to respond after a median follow up of more than 8 months.
MCC is a rare and aggressive form of skin cancer that tends to occur in older individuals and those with a suppressed immune system. About 2,000 new cases are diagnosed annually in the US. In about 80% of cases, the tumors are mainly driven by the Merkel polyomavirus. While 35-fold less common than melanoma, MCC is about three times as likely to result in death of the patient compared to melanoma.
Four patients (three with virus-positive disease) had a complete response, and 10 patients (seven with virus-positive disease) had a partial response.
The phase II noncontrolled trial enrolled 26 patients with advanced MCC who had no prior systemic treatment. Patients received a 2 mg/kg of body weight dose every 3 weeks.
Seventeen patients (65%) had virus-positive tumors. Among these patients, the response rate was 62% (10 of 16 patients). The response rate was 44% (4 of 9 patients) among patients with virus-negative, UV-driven tumors.
“What we found in this preliminary study of patients with Merkel cell cancer may not be true for every virus-induced cancer,” said study author Suzanne Topalian, MD, associate director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy, in a news release. “But if additional studies with more patients confirm our findings, we will have strong reason to believe that many cancers with virus-linked proteins could be valid targets for immune checkpoint blockade.”
After a median follow up of 33 weeks, two of the 14 responding patients relapsed. Duration of response ranged from 2.2 months to at least 9.7 months. At 6 months, the rate of progression-free survival was 67%.
Drug-related grade 3 or 4 adverse events occurred in 15% of patients and were similar to those seen with other pembrolizumab trials. The adverse events were mostly managed with steroid treatment and stopping the study drug. Two patients who developed drug-related toxicities improved with drug discontinuation and corticosteroid treatment. Both patients continued to have antitumor responses months after stopping pembrolizumab, noted Paul Nghiem, MD, PhD, investigator of the Clinical Research Division at Fred Hutchinson Cancer Research Center and professor of medicine, Division of Dermatology, at the University of Washington School of Medicine.
According to Nghiem, the immune system likely recognizes the viral proteins produced by the virus-positive tumors. The immune system likely recognizes virus-negative MCC because these tumors have a high burden of mutations caused by UV light which alters the protein products of these genes, making them “foreign” to the patient’s immune system.
The study was funded by The National Cancer Institute and Merck, which manufacturer’s pembrolizumab.