Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.

Autor:	Nghiem P; 1 University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA., Bhatia S; 1 University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA., Lipson EJ; 2 Johns Hopkins Kimmel Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, MD., Sharfman WH; 2 Johns Hopkins Kimmel Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, MD., Kudchadkar RR; 3 Emory University, Atlanta, GA., Brohl AS; 4 Moffitt Cancer Center, Tampa, FL., Friedlander PA; 5 Mount Sinai Medical Center, New York, NY., Daud A; 6 University of California San Francisco, San Francisco, CA., Kluger HM; 7 Yale University, New Haven, CT., Reddy SA; 8 Stanford University, Stanford, CA., Boulmay BC; 9 Louisiana State University, New Orleans, LA., Riker AI; 9 Louisiana State University, New Orleans, LA., Burgess MA; 10 University of Pittsburgh, Pittsburgh, PA., Hanks BA; 11 Duke University Medical Center, Durham, NC., Olencki T; 12 Ohio State University Comprehensive Cancer Center, Columbus, OH., Margolin K; 13 City of Hope, Duarte, CA., Lundgren LM; 14 Fred Hutchinson Cancer Research Center/Cancer Immunotherapy Trials Network, Seattle, WA., Soni A; 2 Johns Hopkins Kimmel Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, MD., Ramchurren N; 14 Fred Hutchinson Cancer Research Center/Cancer Immunotherapy Trials Network, Seattle, WA., Church C; 15 University of Washington, Seattle, WA., Park SY; 15 University of Washington, Seattle, WA., Shinohara MM; 15 University of Washington, Seattle, WA., Salim B; 16 Axio Research, Seattle, WA., Taube JM; 2 Johns Hopkins Kimmel Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, MD., Bird SR; 17 Merck Research Laboratories, Kenilworth, NJ., Ibrahim N; 17 Merck Research Laboratories, Kenilworth, NJ., Fling SP; 14 Fred Hutchinson Cancer Research Center/Cancer Immunotherapy Trials Network, Seattle, WA., Homet Moreno B; 17 Merck Research Laboratories, Kenilworth, NJ., Sharon E; 18 National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, MD., Cheever MA; 14 Fred Hutchinson Cancer Research Center/Cancer Immunotherapy Trials Network, Seattle, WA., Topalian SL; 2 Johns Hopkins Kimmel Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, MD.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2019 Mar 20; Vol. 37 (9), pp. 693-702. Date of Electronic Publication: 2019 Feb 06.
DOI:	10.1200/JCO.18.01896
Abstrakt:	Purpose: Merkel cell carcinoma (MCC) is an aggressive skin cancer often caused by the Merkel cell polyomavirus. Clinical trials of programmed cell death-1 pathway inhibitors for advanced MCC (aMCC) demonstrate increased progression-free survival (PFS) compared with historical chemotherapy data. However, response durability and overall survival (OS) data are limited. Patients and Methods: In this multicenter phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017), 50 adults naïve to systemic therapy for aMCC received pembrolizumab (2 mg/kg every 3 weeks) for up to 2 years. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Results: Among 50 patients, the median age was 70.5 years, and 64% had Merkel cell polyomavirus-positive tumors. The objective response rate (ORR) to pembrolizumab was 56% (complete response [24%] plus partial response [32%]; 95% CI, 41.3% to 70.0%), with ORRs of 59% in virus-positive and 53% in virus-negative tumors. Median follow-up time was 14.9 months (range, 0.4 to 36.4+ months). Among 28 responders, median response duration was not reached (range, 5.9 to 34.5+ months). The 24-month PFS rate was 48.3%, and median PFS time was 16.8 months (95% CI, 4.6 months to not estimable). The 24-month OS rate was 68.7%, and median OS time was not reached. Although tumor viral status did not correlate with ORR, PFS, or OS, there was a trend toward improved PFS and OS in patients with programmed death ligand-1-positive tumors. Grade 3 or greater treatment-related adverse events occurred in 14 (28%) of 50 patients and led to treatment discontinuation in seven (14%) of 50 patients, including one treatment-related death. Conclusion: Here, we present the longest observation to date of patients with aMCC receiving first-line anti-programmed cell death-1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable OS compared with historical data from patients treated with first-line chemotherapy.
Databáze:	MEDLINE
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