Pembrolizumab Active in Virus-Positive and ‑Negative Advanced Merkel Cell Carcinoma


Key Points

  • Response was achieved in 56% of patients with advanced Merkel cell carcinoma.
  • Response was achieved in 62% of patients with virus-positive tumors and 44% of those with virus-negative tumors.

The PD-1 (programmed cell death protein 1) inhibitor pembrolizumab (Keytruda) was active in advanced Merkel cell carcinoma in both Merkel cell polyomavirus (MCP)-positive and -negative tumors, according to Nghiem et al, who reported their phase II study findings in The New England Journal of Medicine. Merkel cell tumors often express PD-1, as do MCP-specific T cells.

Study Details

In the study, 25 evaluable patients, including 16 with virus-positive tumors, who had received no previous systemic therapy, were treated with pembrolizumab at 2 mg/kg every 3 weeks. The primary endpoint was objective response rate.

Response Rates

The objective response rate was 56% (95% confidence interval [CI] = 35%–76%), with 4 patients (16%) having a complete response and 10 patients (40%) having a partial response. At median follow-up of 33 weeks (range = 7–53 weeks), relapse had occurred in 2 (14%) of 14 patients with response.

Response duration ranged from 2.2+ months to 9.7+ months. Six-month progression-free survival was 67% (95% CI = 49%–86%). Response was observed in 10 of 16 patients (62%) with virus-positive tumors and 4 of 9 patients (44%) with virus-negative tumors.

Adverse Events

The most common adverse events were fatigue and laboratory abnormalities. Drug-related grade 3 or 4 adverse events occurred in 15% of patients. Grade 4 adverse events consisted of myocarditis in one patient after one dose of pembrolizumab and elevated alanine transaminase and aspartate transaminase in one patient after two doses of pembrolizumab; both had improvement in these adverse events after discontinuation of pembrolizumab and initiation of glucocorticoid treatment, and both had tumor regression, which was ongoing at the time of analysis.

The investigators concluded: “In this study, first-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56%. Responses were observed in patients with virus-positive tumors and those with virus-negative tumors.”

The study was funded by the National Cancer Institute and Merck.

Suzanne L. Topalian, MD, of Johns Hopkins University School of Medicine and Sidney Kimmel Cancer Center, and Martin A. Cheever, MD, of Fred Hutchinson Cancer Research Center, contributed equally to the New England Journal of Medicine article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.