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Pooling 2,159 patients from six trials showed that which side of the colon a tumour started on decides whether an EGFR antibody helps at all: a clear survival gain on the left, none on the right.
Arnold, Lueza, Douillard and colleagues retrospectively investigated the influence of primary tumour location in patients with unresectable RAS wild-type metastatic colorectal cancer in six randomised trials (CRYSTAL, FIRE-3, CALGB 80405, PRIME, PEAK and 20050181), comparing chemotherapy plus an EGFR antibody with chemotherapy or chemotherapy plus bevacizumab. Hazard ratios for overall and progression-free survival and odds ratios for response were pooled across studies, and the predictive value was evaluated by pooling the study-level interaction between treatment effect and tumour side.
Primary tumour location and RAS status were available for 2,159 of the 5,760 randomised patients (37.5 percent): 515 right-sided and 1,644 left-sided.
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 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.
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.
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.
Shares Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME), CRYSTAL & FIRE-3, Eric Van Cutsem, Sidedness (left vs right colon) 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 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 Heinz-Josef Lenz, Josep Tabernero, 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, Eric Van Cutsem, 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 and the tag colorectal-evidence.
Shares Heinz-Josef Lenz, Eric Van Cutsem, 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 and the tag colorectal-evidence.
Shares FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3), VEGF / VEGFR, Bevacizumab, KRAS and the tag colorectal-evidence.
Shares Andrés Cervantes, Annals of Oncology, Colorectal cancer and the tag colorectal-evidence.