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BRAF V600E bowel cancer had a median survival of four to six months after first-line failure. Blocking BRAF and EGFR together took it to nine, and made the doublet a standard.
Kopetz, Grothey, Yaeger and colleagues enrolled 665 patients with BRAF V600E-mutated metastatic colorectal cancer who had progressed after one or two previous regimens, randomising them 1:1:1 to encorafenib, binimetinib and cetuximab (triplet), encorafenib and cetuximab (doublet), or the investigators' choice of cetuximab with irinotecan or with FOLFIRI (control). The primary end points were overall survival and objective response in the triplet group against control, with overall survival in the doublet group against control as a secondary end point; this is the prespecified interim analysis.
Inhibition of BRAF alone has limited activity in colorectal cancer because the pathway reactivates through EGFR signalling, which is the reason the EGFR antibody is in every arm of the experimental design.
Encorafenib with cetuximab became the standard second-line treatment for BRAF V600E disease, and the platform BREAKWATER later moved into first line with chemotherapy added, doubling survival again.
Shares Eric Van Cutsem, Irinotecan (and liposomal irinotecan), FOLFIRI (5-FU, leucovorin, irinotecan), Cetuximab and the tag colorectal-evidence.
Shares FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of TRIBE, Irinotecan (and liposomal irinotecan), FOLFIRI (5-FU, leucovorin, irinotecan), Cetuximab and the tag colorectal-evidence.
Shares Josep Tabernero, 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 and the tag colorectal-evidence.
Shares Josep Tabernero, BRAF, 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, RAS / RAF / MEK / ERK (MAPK) and the tag colorectal-evidence.
Shares Takayuki Yoshino, Eric Van Cutsem, Acquired resistance to every therapy, 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 Josep Tabernero, Eric Van Cutsem, Cetuximab, 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 Acquired resistance to every therapy, 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, RAS / RAF / MEK / ERK (MAPK), EGFR 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.