Median follow-up for the final overall survival analysis was 44.5 months (interquartile range = 39.7–49.8 months). The co-primary endpoints were overall survival and progression-free survival in the intention-to-treat population. Patients receiving chemotherapy could cross over to pembrolizumab for up to 35 cycles after disease progression. Pembrolizumab was given until disease progression, unacceptable toxicity, or for a maximum of 35 cycles. In the open-label trial, 307 patients were randomly assigned between February 2016 and February 2018 to receive pembrolizumab at 200 mg every 3 weeks (n = 153) or investigator’s choice of chemotherapy (n = 154) with mFOLFOX6 (oxaliplatin, leucovorin, fluorouracil) or FOLFIRI (irinotecan, leucovorin, fluorouracil) with or without bevacizumab or cetuximab. Progression-free survival results were previously reported.
#Keynote 177 trial#
The trial supported the June 2020 approval of pembrolizumab in this setting on the basis of improved progression-free survival. However, 60% of the chemotherapy group crossed over to receive anti–PD-1 or anti–PD-L1 therapy upon disease progression. (Funded by Merck Sharp and Dohme and by Stand Up to Cancer KEYNOTE-177 number, NCT02563002.).As reported in The Lancet Oncology by Diaz et al, the final overall survival analysis of the phase III KEYNOTE-177 trial did not show a significant improvement with pembrolizumab vs chemotherapy in patients with newly diagnosed microsatellite instability–high or mismatch repair–deficient metastatic colorectal cancer. CONCLUSIONS: Pembrolizumab led to significantly longer progression-free survival than chemotherapy when received as first-line therapy for MSI-H-dMMR metastatic colorectal cancer, with fewer treatment-related adverse events. Treatment-related adverse events of grade 3 or higher occurred in 22% of the patients in the pembrolizumab group, as compared with 66% (including one patient who died) in the chemotherapy group. Among patients with an overall response, 83% in the pembrolizumab group, as compared with 35% of patients in the chemotherapy group, had ongoing responses at 24 months.
An overall response (complete or partial response), as evaluated with Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was observed in 43.8% of the patients in the pembrolizumab group and 33.1% in the chemotherapy group. Data on overall survival were still evolving (66% of required events had occurred) and remain blinded until the final analysis. As of the data cutoff date, 56 patients in the pembrolizumab group and 69 in the chemotherapy group had died. The estimated restricted mean survival after 24 months of follow-up was 13.7 months (range, 12.0 to 15.4) as compared with 10.8 months (range, 9.4 to 12.2). RESULTS: At the second interim analysis, after a median follow-up (from randomization to data cutoff) of 32.4 months (range, 24.0 to 48.3), pembrolizumab was superior to chemotherapy with respect to progression-free survival (median, 16.5 vs. The two primary end points were progression-free survival and overall survival. Patients receiving chemotherapy could cross over to pembrolizumab therapy after disease progression. METHODS: In this phase 3, open-label trial, 307 patients with metastatic MSI-H-dMMR colorectal cancer who had not previously received treatment were randomly assigned, in a 1:1 ratio, to receive pembrolizumab at a dose of 200 mg every 3 weeks or chemotherapy (5-fluorouracil-based therapy with or without bevacizumab or cetuximab) every 2 weeks. The efficacy of PD-1 blockade as compared with chemotherapy as first-line therapy for MSI-H-dMMR advanced or metastatic colorectal cancer is unknown.
Science & Technology, Life Sciences & Biomedicine, Medicine, General & Internal, General & Internal Medicine, DEFICIENT, TUMORS, BRAF, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Brain Neoplasms, Colorectal Neoplasms, Female, Fluorouracil, Humans, Immune Checkpoint Inhibitors, Kaplan-Meier Estimate, Male, Microsatellite Instability, Middle Aged, Mutation, Neoplastic Syndromes, Hereditary, Progression-Free Survival, KEYNOTE-177 Investigators, 11 Medical and Health SciencesīACKGROUND: Programmed death 1 (PD-1) blockade has clinical benefit in microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) tumors after previous therapy. Shiu, K-K Kim, TW Jensen, B Jensen, LH Punt, C Smith, D Garcia-Carbonero, R Benavides, M Gibbs, P de la Fouchardiere, C Rivera, F Elez, E Bendell, J Le, DT Yoshino, T Van Cutsem, E Yang, P Farooqui, MZH Marinello, P Diaz, LA Keywords:
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