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Proved that for RAS-normal tumours starting on the left side of the colon, an EGFR antibody beats the VEGF antibody as first partner for chemotherapy.
Left-sided primaries: OS 37.9 vs 34.3 months (HR 0.82), the longest median OS in a first-line phase 3 at the time; no benefit in right-sided tumours. Confirmed the sidedness principle from FIRE-3 and CALGB 80405 subgroup analyses and made 'left-sided, RAS/BRAF wild-type' the anti-EGFR population in guidelines.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
823 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival, left-sidedprimary | Panitumumab + mFOLFOX6 | - | 37.9 months | 0.82 (0.68 to 0.99) | 0.031 | link |
| Bevacizumab + mFOLFOX6 | - | 34.3 months |
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.
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.
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 Anti-EGFR antibody + chemotherapy in left-sided RAS/BRAF wild-type mCRC, OPUS, CALGB/SWOG 80405, PRIME.
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), 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.
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), 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.
Shares OPUS, PRIME, EGFR, Monoclonal antibodies.
Shares Sidedness (left vs right colon), Panitumumab, EGFR, Colon cancer (adenocarcinoma of the colon).
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, 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, RAS wild-type (extended KRAS and NRAS testing).
Shares Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer (PRIME), 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.
Shares Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up, 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, EGFR.