Pembrolizumab versus chemotherapy in microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer: 5-year follow-up from the randomized phase III KEYNOTE-177 study

作者：Thierry André, Kai Keen Shiu, Tae Won Kim, Benny Vittrup Jensen, Lars Henrik Jensen, C.J.A. Punt, Denis Michel Smith, R. Garcia-Carbonero, Julia Alcaide, Peter Gibbs, Christelle de la Fouchardière, Fernanda Estefanía Rivera, Elena Élez, Dung Thi Le, Takashi Yoshino, Yu Zuo, D. Fogelman, David Eli Adelberg, Luis Alberto Diaz · 发表于：Annals of Oncology · 年份：2024 · DOI：10.1016/j.annonc.2024.11.012 · 被引用次数：134 · 研究领域：Genetic factors in colorectal cancer、Cancer Immunotherapy and Biomarkers、Colorectal Cancer Treatments and Studies

BACKGROUND: Results from the phase III KEYNOTE-177 study established pembrolizumab as a new first-line standard of care for microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Previous results from KEYNOTE-177 showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with pembrolizumab versus chemotherapy ± bevacizumab/cetuximab in MSI-H/dMMR mCRC. Results after >5 years of follow-up are reported. PATIENTS AND METHODS: Adults with untreated MSI-H/dMMR mCRC were randomly assigned 1 : 1 to receive pembrolizumab 200 mg intravenously every 3 weeks or chemotherapy. Patients assigned to chemotherapy could cross over to pembrolizumab after centrally confirmed progressive disease. Dual primary endpoints were PFS per RECIST v1.1 and overall survival (OS). Secondary endpoints included duration of response and safety. RESULTS: At data cut-off (17 July 2023), median follow-up was 73.3 months (range, 64.9-89.2 months). Overall, 307 patients were assigned to receive pembrolizumab (n = 153) or chemotherapy (n = 154). Fifty-seven (37.0%) patients assigned to chemotherapy crossed over to pembrolizumab per protocol; 39 (25.3%) received a programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] inhibitor off protocol (effective crossover rate, 62%). Median OS was 77.5 months with pembrolizumab versus 36.7 months with chemotherapy (hazard ratio, 0.73; 95% confidence interval 0....