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PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma
Paul T Nghiem1, Shailender Bhatia1, Evan J Lipson1
1From the University of Washington Medical Center (P.T.N., S. Bhatia, N.J.M., E.M.S., M.M.S., J.A.T., M.A.C.), Fred Hutchinson Cancer Research Center (P.T.N., S. Bhatia, S.P.F., L.L., J.A.T., M.A.C.), Cancer Immunotherapy Trials Network (S.P.F., L.L., M.A.C.), and Cancer Research and Biostatistics (A.M., L.R.S.) - all in Seattle; Johns Hopkins University School of Medicine and Kimmel Cancer Center, Baltimore (E.J.L., S. Berry, D.M.P., W.H.S., J.C.S., J.M.T., S.L.T.), and Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda. (E.S.) - both in Maryland; Winship Cancer Institute of Emory University, Atlanta (R.R.K.); Merck Research Laboratories, Kenilworth, NJ (L.A., E.K.C., S.M.T., J.H.Y.); University of California, San Francisco, San Francisco (A.D.), and Stanford University, Stanford (H.E.K., K.M., S.A.R.) - both in California; Mt. Sinai Medical Center, New York (P.A.F.); Yale University, New Haven, CT (H.M.K.); and Ohio State University, Columbus (T.O.).
Background:
Merkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T cells express PD-1.
Methods:
In this multicenter, phase 2, noncontrolled study, we assigned adults with advanced Merkel-cell carcinoma who had received no previous systemic therapy to receive pembrolizumab (anti-PD-1) at a dose of 2 mg per kilogram of body weight every 3 weeks. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Efficacy was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing.
Results:
A total of 26 patients received at least one dose of pembrolizumab. The objective response rate among the 25 patients with at least one evaluation during treatment was 56% (95% confidence interval [CI], 35 to 76); 4 patients had a complete response, and 10 had a partial response. With a median follow-up of 33 weeks (range, 7 to 53), relapses occurred in 2 of the 14 patients who had had a response (14%). The response duration ranged from at least 2.2 months to at least 9.7 months. The rate of progression-free survival at 6 months was 67% (95% CI, 49 to 86). A total of 17 of the 26 patients (65%) had virus-positive tumors. The response rate was 62% among patients with MCPyV-positive tumors (10 of 16 patients) and 44% among those with virus-negative tumors (4 of 9 patients). Drug-related grade 3 or 4 adverse events occurred in 15% of the patients.
Conclusions:
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. (Funded by the National Cancer Institute and Merck; ClinicalTrials.gov number, NCT02267603.).
Insights
First-line pembrolizumab showed a 56% objective response rate in advanced Merkel-cell carcinoma patients. Responses were seen in both virus-positive and virus-negative tumors, indicating broad efficacy for this immunotherapy.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Merkel-cell carcinoma (MCC) is an aggressive skin cancer.
- MCC is associated with ultraviolet light exposure and Merkel-cell polyomavirus (MCPyV).
- Current treatments like chemotherapy offer transient responses.
Purpose of the Study:
- To evaluate the efficacy of pembrolizumab (anti-PD-1) as a first-line treatment for advanced MCC.
- To assess the objective response rate (ORR) in patients with advanced MCC receiving pembrolizumab.
- To correlate treatment efficacy with MCPyV viral status.
Main Methods:
- A multicenter, phase 2, noncontrolled study.
- 26 adults with advanced MCC received pembrolizumab (2 mg/kg every 3 weeks) as first-line therapy.
- Objective response rate was the primary endpoint, assessed by RECIST v1.1.
Main Results:
- The objective response rate was 56% (25 patients evaluated).
- Complete response in 4 patients, partial response in 10 patients.
- Progression-free survival at 6 months was 67%; 65% of patients had virus-positive tumors.
Conclusions:
- First-line pembrolizumab demonstrated a 56% objective response rate in advanced MCC.
- Responses were observed in both MCPyV-positive and MCPyV-negative tumors.
- Pembrolizumab represents a promising first-line treatment option for advanced MCC.
