TY - JOUR
T1 - Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line therapy
AU - Nghiem, Paul
AU - Bhatia, Shailender
AU - Lipson, Evan J.
AU - Sharfman, William H.
AU - Kudchadkar, Ragini R.
AU - Brohl, Andrew S.
AU - Friedlander, Phillip A.
AU - Daud, Adil
AU - Kluger, Harriet M.
AU - Reddy, Sunil A.
AU - Boulmay, Brian C.
AU - Riker, Adam I.
AU - Burgess, Melissa A.
AU - Hanks, Brent A.
AU - Olencki, Thomas
AU - Margolin, Kim
AU - Lundgren, Lisa M.
AU - Soni, Abha
AU - Ramchurren, Nirasha
AU - Church, Candice
AU - Park, Song Y.
AU - Shinohara, Michi M.
AU - Salim, Bob
AU - Taube, Janis M.
AU - Bird, Steven R.
AU - Ibrahim, Nageatte
AU - Fling, Steven P.
AU - Moreno, Blanca Homet
AU - Sharon, Elad
AU - Cheever, Martin A.
AU - Topalian, Suzanne L.
N1 - Publisher Copyright:
Copyright © 2019 American Society of Clinical Oncology. All rights reserved.
PY - 2019/3/20
Y1 - 2019/3/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85062068079&partnerID=8YFLogxK
U2 - 10.1200/JCO.18.01896
DO - 10.1200/JCO.18.01896
M3 - Article
C2 - 30726175
AN - SCOPUS:85062068079
SN - 0732-183X
VL - 37
SP - 693
EP - 702
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -