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KRAS G12C inhibitors alone barely work in bowel cancer because the tumour switches EGFR back on. Blocking both at once more than doubled progression-free survival against standard refractory treatment.
Fakih, Salvatore, Esaki and colleagues assigned patients with chemorefractory metastatic colorectal cancer carrying a KRAS G12C mutation, who had not previously received a KRAS G12C inhibitor, to sotorasib 960 mg daily plus panitumumab (53 patients), sotorasib 240 mg daily plus panitumumab (53 patients), or the investigator's choice of trifluridine-tipiracil or regorafenib (54 patients). The primary end point was progression-free survival by blinded independent central review; key secondary end points were overall survival and objective response.
KRAS G12C occurs in approximately 3 to 4 percent of patients with metastatic colorectal cancer, and monotherapy with KRAS G12C inhibitors had yielded only modest efficacy.
The proof that a RAS inhibitor in colorectal cancer needs an EGFR antibody beside it, a principle that now shapes the trials of the pan-RAS and G12D inhibitors following behind.
Shares Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME), 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 Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME), Panitumumab, 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 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 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, EGFR, KRAS, Monoclonal antibodies and the tag colorectal-evidence.
Shares Regorafenib, 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, Colorectal cancer and the tag colorectal-evidence.
Shares 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, EGFR, KRAS, Monoclonal antibodies and the tag colorectal-evidence.
Shares 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), KRAS, New England Journal of Medicine and the tag colorectal-evidence.
Shares Trifluridine/tipiracil, 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, Colorectal cancer and the tag colorectal-evidence.