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Where in the colon a tumour starts changes its biology and which drugs work. Left-sided tumours respond to EGFR antibodies; right-sided ones do not.
Right-sided (caecum to transverse) tumours are more often dMMR, BRAF-mutant, mucinous, and worse prognosis; left-sided (splenic flexure to rectum) are more often chromosomally unstable and EGFR-dependent. CALGB 80405, FIRE-3, and PARADIGM showed anti-EGFR benefit is confined to left-sided RAS wild-type disease. Embryologic origin (midgut vs hindgut) underlies the difference.
In plain words · A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
Showing the target this term concerns: EGFR.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
This is the European standard the UK and NHS page for colorectal cancer is compared against; NICE NG151 covers the same ground for England with a narrower set of funded drugs.
This is the paper Europe PMC returns for registry id NCT02394795 with the most citations, so it is the natural first reading for anyone following the PARADIGM trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
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.
It is the caution attached to the sidedness rule: a tumour at the hepatic flexure and one at the caecum are both called right-sided and are not the same disease.
It turned sidedness from an epidemiological curiosity into a mechanistic statement, and it is the reason a wild-type mitogenic report on a left-sided tumour is read as ligand dependence rather than as an absence.
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.
It stops a BRAF-mutant report being read as one uniform outlook, and it separates the class II and III mutations, which signal differently and are not covered by the encorafenib plus cetuximab label, from V600E.
It showed the sidedness effect is not an artefact of pooling and survives adjustment for BRAF, which is what made guideline committees act on it.
Shares Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC, Anti-EGFR rechallenge, CAIRO5, PRIME.
Shares Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up, Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials, Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer (CRYSTAL), CRYSTAL & FIRE-3.
Shares Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial, Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials, Clinical sequencing defines the genomic landscape of metastatic colorectal cancer, Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME).
Shares Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up, Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC), Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME), 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.
Shares PRIME, PARADIGM, CRYSTAL & FIRE-3, RAS wild-type (extended KRAS and NRAS testing).
Shares Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up, Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer, Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC), BRAF V600E-mutant colorectal cancer.
Shares Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials, FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3), CRYSTAL & FIRE-3, 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.
Shares Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial, Extended RAS testing, PRIME, Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME).