TY - JOUR
T1 - PD-1 blockade with pembrolizumab in advanced merkel-cell carcinoma
AU - Nghiem, Paul T.
AU - Bhatia, Shailender
AU - Lipson, Evan J.
AU - Kudchadkar, Ragini R.
AU - Miller, Natalie J.
AU - Annamalai, Lakshmanan
AU - Berry, Sneha
AU - Chartash, Elliot K.
AU - Daud, Adil
AU - Fling, Steven P.
AU - Friedlander, Philip A.
AU - Kluger, Harriet M.
AU - Kohrt, Holbrook E.
AU - Lundgren, Lisa
AU - Margolin, Kim
AU - Mitchell, Alan
AU - Olencki, Thomas
AU - Pardoll, Drew M.
AU - Reddy, Sunil A.
AU - Shantha, Erica M.
AU - Sharfman, William H.
AU - Sharon, Elad
AU - Shemanski, Lynn R.
AU - Shinohara, Michi M.
AU - Sunshine, Joel C.
AU - Taube, Janis M.
AU - Thompson, John A.
AU - Townson, Steven M.
AU - Yearley, Jennifer H.
AU - Topalian, Suzanne L.
AU - Cheever, Martin A.
N1 - Publisher Copyright:
Copyright © 2016 Massachusetts Medical Society.
PY - 2016/6/30
Y1 - 2016/6/30
N2 - 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 Merkelcell 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.
AB - 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 Merkelcell 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.
UR - http://www.scopus.com/inward/record.url?scp=84976511909&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84976511909&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1603702
DO - 10.1056/NEJMoa1603702
M3 - Article
C2 - 27093365
AN - SCOPUS:84976511909
SN - 0028-4793
VL - 374
SP - 2542
EP - 2552
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 26
ER -