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Looking beyond the one KRAS exon everyone tested found that a further 17 percent of patients carried a RAS mutation and were harmed rather than helped by the antibody. Testing widened overnight.
Douillard, Oliner, Siena and colleagues assessed the efficacy and safety of panitumumab plus FOLFOX4 against FOLFOX4 alone by RAS (KRAS or NRAS) and BRAF mutation status, in a prospective-retrospective analysis of PRIME. Six hundred and thirty-nine patients whose tumours had no KRAS exon 2 mutation had results for at least one of KRAS exon 3 or 4, NRAS exon 2, 3 or 4, or BRAF exon 15; the overall rate of RAS status ascertainment was 90 percent.
No new safety signals were identified, and BRAF mutation was a negative prognostic factor rather than a predictor of antibody benefit.
Extended RAS testing (KRAS and NRAS exons 2, 3 and 4) became the standard before any EGFR antibody, and about one in six patients who would previously have been treated is now spared a drug that would have made things worse.
Patients with metastatic colorectal cancer carrying a KRAS G12C mutation (about 3-4% of cases) who have exhausted standard chemotherapy now have a targeted option that works far better than trifluridine-tipiracil or regorafenib. The higher sotorasib dose is clearly superior, and the EGFR antibody is essential because KRAS inhibition alone has little effect in bowel cancer. Responses are still modest and short-lived compared with EGFR or ALK inhibitors in lung cancer.
The analysis that put 'left-sided, RAS and BRAF wild-type' into every guideline as the anti-EGFR population, and made an anatomical fact into a treatment-selection biomarker.
Biomarker-directed treatment in colorectal cancer starts here: RAS testing became mandatory before an EGFR antibody, and the corpus's updated CRYSTAL analysis (paper-kras-colorectal-j-clin-oncol-2011) carries the mature survival figures in the wild-type group.
One of the most cited trial reports Europe PMC returns for KRAS in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
Shares Josep Tabernero, Sidedness (left vs right colon), 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 and the tag colorectal-evidence.
Shares Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials, Sidedness (left vs right colon), 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, FOLFOX (5-FU, leucovorin, oxaliplatin) and the tag colorectal-evidence.
Shares Josep Tabernero, PARADIGM, Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials, Sidedness (left vs right colon) and the tag colorectal-evidence.
Shares Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials, Sidedness (left vs right colon), 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 and the tag colorectal-evidence.
Shares Josep Tabernero, Oxaliplatin, 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, FOLFOX (5-FU, leucovorin, oxaliplatin) and the tag colorectal-evidence.
Shares Panitumumab, Oxaliplatin, 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, FOLFOX (5-FU, leucovorin, oxaliplatin) and the tag colorectal-evidence.
Shares Salvatore Siena, 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, KRAS, Monoclonal antibodies and the tag colorectal-evidence.
Shares Oxaliplatin, 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, FOLFOX (5-FU, leucovorin, oxaliplatin), New England Journal of Medicine and the tag colorectal-evidence.