Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 Study.

• DOI: 10.1200/jco.2020.38.18_suppl.lba4
• Publication Date: 2020-06-01T15:48:26Z
• Authors: Thierry Andre; Kai-Keen Shiu; Tae Won Kim; Benny Vittrup Jensen; Lars Henrik Jensen; Cornelis J. A. Punt; Denis Michel Smith; Rocio Garcia-Carb...; Manuel Benavides; Peter Gibbs; Christelle De La ...; Fernando Rivera; Elena Elez; Johanna C. Bendell; Dung T. Le; Takayuki Yoshino; Ping Yang; Mohammed Zulfiqar...; Patricia Marinello; Luis A. Diaz
• Keywords: FOLFIRI; Panitumumab; Clinical endpoint; Microsatellite Instability

LBA4 Background: KEYNOTE-177 (NCT02563002) is a phase 3, randomized open-label study evaluating the efficacy and safety of pembrolizumab (pembro) versus standard care chemotherapy ± bevacizumab or cetuximab (chemo) as first-line therapy for patients (pts) with microsatellite-instability high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). We present results final PFS analysis. Methods: A total 307 pts MSI-H/dMMR mCRC determined locally ECOG PS 0 1 were randomly assigned 1:1 to pembro 200 mg Q3W up 2 years investigator’s choice mFOLFOX6 FOLFIRI Q2W (chemo chosen prior randomization). Treatment continued until PD, unacceptable toxicity, pt/investigator decision withdraw, completion 35 cycles (pembro only). Patients receiving chemo could crossover after confirmed PD. Primary end points (RECIST v1.1, central review) OS. Key secondary included ORR review), safety. The data cutoff date this interim analysis was Feb 19, 2020. will continue without changes evaluate Results: At cutoff, 153 154 chemo. Median (range) follow-up 28.4 mo (0.2-48.3) vs 27.2 (0.8-46.6) Pembro superior (median 16.5 8.2 mo; HR 0.60; 95% CI, 0.45-0.80; P=0.0002). 12- 24-mo rates 55.3% 48.3% 37.3% 18.6% Confirmed 43.8% 33.1%; median duration response not reached (2.3+ 41.4+) 10.6 (2.8 37.5+) Grade 3-5 treatment related adverse event (AE) 22% 66% One pt in arm died due treatment-related AE. Conclusions: provided clinically meaningful statistically significant improvement mCRC, fewer AEs observed should be new these pts. Clinical trial information: NCT02563002 .