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A head-to-head of the two antibodies. They tied on response and progression, but patients on the EGFR antibody lived 3.7 months longer, a result nobody had predicted from the primary endpoint.
Heinemann, von Weikersthal, Decker and colleagues recruited patients aged 18 to 75 with stage IV histologically confirmed colorectal cancer, ECOG performance status 0 to 2 and KRAS exon 2 codon 12/13 wild-type tumours from centres in Germany and Austria, randomising them 1:1 to FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab. The primary endpoint was objective response, analysed by intention to treat.
Between January 2007 and September 2012, 592 patients with KRAS exon 2 wild-type tumours were randomised and treated. The discordance between response, progression-free survival and overall survival in this trial is the reason later analyses went looking for sidedness.
Together with PARADIGM it makes the EGFR antibody the preferred first partner for chemotherapy in left-sided RAS wild-type disease; the survival gain without a progression-free survival gain remains one of the field's unexplained results.
The negative counterweight to FIRE-3. The two trials are reconciled only by primary tumour side, which is why the sidedness analysis rather than either trial is what guidelines now cite.
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.
The triplet is the option for fit patients who need a response, particularly in BRAF-mutant and right-sided disease where the EGFR antibody route is closed; it also quantified how much worse BRAF-mutant disease was before BEACON and BREAKWATER.
Shares CRYSTAL & FIRE-3, Sidedness (left vs right colon), Irinotecan (and liposomal irinotecan), FOLFIRI (5-FU, leucovorin, irinotecan) 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 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 VEGF / VEGFR, 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, Anti-angiogenic therapy, Bevacizumab 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, The Lancet Oncology, KRAS, Monoclonal antibodies and the tag colorectal-evidence.
Shares VEGF / VEGFR, 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, Anti-angiogenic therapy, 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 VEGF / VEGFR, 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, Anti-angiogenic therapy, Colorectal cancer and the tag colorectal-evidence.