Pembrolizumab therapy for microsatellite instability high (MSI-H) colorectal cancer (CRC) and non-CRC.

作者：Luis Alberto Diaz, Aurélien Marabelle, Jean‐Pierre Delord, Ronnie Shapira‐Frommer, Ravit Geva, Nir Peled, Tae Won Kim, Thierry André, Eric Van Cutsem, Rosine Guimbaud, Dirk Jaeger, Elena Élez, Takayuki Yoshino, Andrew K. Joe, Baohoang Lam, Christine K. Gause, Scott Knowles Pruitt, Soonmo Peter Kang, Dung Thi Le · 发表于：Journal of Clinical Oncology · 年份：2017 · DOI：10.1200/jco.2017.35.15_suppl.3071 · 被引用次数：126 · 研究领域：Genetic factors in colorectal cancer、Cancer Immunotherapy and Biomarkers、Colorectal Cancer Treatments and Studies

3071 Background: Mismatch repair deficient cancers harbor high levels of microsatellite instability and somatic mutations. Treatment with anti-PD-1 antibodies has resulted in durable objective responses in MSI-H cancer. As part of the ongoing, global, multicenter phase 2 studies KEYNOTE(KN)164 and KN158, we assessed the efficacy of pembrolizumab in patients (pts) with MSI-H tumors. Methods: Both studies enrolled pts with MSI-H status determined locally by IHC or PCR. KN164 enrolled pts with MSI-H CRC and ≥2 prior therapies, whereas the multicohortKN158 study included pts with MSI-H non-CRC and ≥1 prior therapy. Eligible pts in both studies received pembrolizumab 200 mg Q3W until progression, unacceptable toxicity, or pt/investigator decision. Tumor response was assessed every 9 wk by independent review per RECIST v1.1. Primary endpoint was ORR. Secondary endpoints included DOR, PFS, OS, and safety. Analyses were performed in pts from KN164 and KN158 who had ≥27 wk of follow-up as of Aug 3, 2016 and Oct 19, 2016, respectively. Results: KN164 enrolled 61 pts with MSI-H CRC (90% with ≥2 prior therapies) whereas KN158 included 21 pts with MSI-H non-CRC (42% with ≥2 prior therapies). In KN158 the most common tumor types were endometrial and small intestinal cancer (n = 4 each), cholangiocarcinoma (n = 3), and gastric and pancreatic cancer (n = 2 each). Median follow-up was 7.4 mo for MSI-H CRC and 4.5 mo for MSI-H non-CRC. ORR for MSI-H CRC was 26.2% (95% CI, 15.8%-39.1%), with 15...