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The randomised trial that replaced chemotherapy with a single antibody as the first treatment for the 5 percent of metastatic bowel cancers with a broken DNA spell-checker: 16.5 against 8.2 months without progression, and a quarter of the severe side effects.
André, Shiu, Kim and colleagues randomly assigned 307 patients with previously untreated metastatic microsatellite-instability-high or mismatch repair-deficient colorectal cancer 1:1 to pembrolizumab 200 mg every three weeks or to fluorouracil-based chemotherapy with or without bevacizumab or cetuximab every two weeks, with crossover to pembrolizumab permitted after progression on chemotherapy. The two primary end points were progression-free survival and overall survival.
Among patients with an overall response, 83 percent in the pembrolizumab group against 35 percent in the chemotherapy group had ongoing responses at 24 months, which is the durability that distinguishes checkpoint blockade from chemotherapy in this population.
First-line chemotherapy-free treatment for mismatch repair-deficient metastatic colorectal cancer, approved in June 2020; the five-year follow-up published in 2024 reported median overall survival of 77.5 months despite 62 percent crossover.
Combination checkpoint blockade became a first-line standard for mismatch repair-deficient metastatic colorectal cancer in 2025; the later all-lines comparison against nivolumab alone showed the CTLA-4 antibody adds to the PD-1 antibody, the first phase 3 to prove that in this disease.
The paper that split colorectal cancer into two diseases for immunotherapy purposes, and the direct ancestor of the first tumour-agnostic drug approval two years later.
Shares Luis A. Diaz Jr., PD-1 blockade in tumors with mismatch-repair deficiency, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR) and the tag colorectal-evidence.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Mismatch-repair deficient (MSI-high) colorectal cancer, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares Takayuki Yoshino, Eric Van Cutsem, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, New England Journal of Medicine and the tag colorectal-evidence.
Shares Thierry André, Takayuki Yoshino, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, New England Journal of Medicine and the tag colorectal-evidence.
Shares PD-1 blockade in tumors with mismatch-repair deficiency, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, PD-1 and the tag colorectal-evidence.
Shares PD-1 blockade in tumors with mismatch-repair deficiency, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, PD-1 and the tag colorectal-evidence.
Shares KEYNOTE-177, Eric Van Cutsem, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer and the tag colorectal-evidence.
Shares Takayuki Yoshino, Eric Van Cutsem, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.