Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability–High/Mismatch Repair–Deficient Metastatic Colorectal Cancer: KEYNOTE-164

作者：Dung T. Le, Tae Won Kim, Eric Van Cutsem, Ravit Geva, Dirk Jäger, Hiroki Hara, Matthew Burge, Bert H. O’Neil, Petr Kavan, Takayuki Yoshino, Rosine Guimbaud, Hiroya Taniguchi, Elena Élez, Salah‐Eddin Al‐Batran, Patrick M. Boland, Todd S. Crocenzi, Chloé E. Atreya, Yi Cui, Tong Dai, Patricia Marinello, Luis A. Díaz, Thierry André · 发表于：Journal of Clinical Oncology · 年份：2019 · DOI：10.1200/jco.19.02107 · 被引用次数：1032 · 研究领域：Cancer Immunotherapy and Biomarkers、Genetic factors in colorectal cancer、Colorectal Cancer Treatments and Studies

PURPOSE: KEYNOTE-164 (NCT02460198) evaluated the antitumor activity of pembrolizumab in previously treated, metastatic, microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC). METHODS: This phase II open-label study involved 128 centers worldwide. Eligible patients were age ≥ 18 years and had metastatic MSI-H/dMMR CRC treated with ≥ 2 prior lines of standard therapy, including fluoropyrimidine, oxaliplatin, and irinotecan with or without anti-vascular endothelial growth factor/epidermal growth factor receptor monoclonal antibody (cohort A) or ≥ 1 prior line of therapy (cohort B). MSI-H/dMMR status was assessed locally. Patients received pembrolizumab 200 mg every 3 weeks for up to 2 years until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate by RECIST version 1.1 by independent central review. Secondary end points were duration of response, progression-free survival (PFS), overall survival, safety, and tolerability. RESULTS: A total of 124 patients with MSI-H/dMMR CRC (61 in cohort A, 63 in cohort B) enrolled. At data cutoff, median follow-up was 31.3 months (range, 0.2-35.6 months) for cohort A and 24.2 months (range, 0.1-27.1 months) for cohort B. Objective response rate was 33% (95% CI, 21% to 46%) and 33% (95% CI, 22% to 46%), respectively, with median duration of response not reached in either cohort. Median PFS was 2.3 months (95% CI, 2.1 to 8.1 months) and 4.1 months (95% CI, 2...