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The trial that widened the RAS test from two spots in one gene to all of KRAS and NRAS, because patients with any RAS mutation were harmed by the antibody.
PRIME randomised 1,183 patients with previously untreated metastatic colorectal cancer to FOLFOX4 with or without panitumumab. The prospective-retrospective RAS analysis tested KRAS exons 3 and 4 and NRAS exons 2, 3 and 4 in patients without KRAS exon 2 mutations, with 90 percent ascertainment. Among 512 patients without any RAS mutation, progression-free survival was 10.1 against 7.9 months (hazard ratio 0.72, 95% CI 0.58 to 0.90, p=0.004) and overall survival 26.0 against 20.2 months (hazard ratio 0.78, 0.62 to 0.99, p=0.04). A further 108 patients, 17 percent of those with wild-type KRAS exon 2, carried other RAS mutations, and in them panitumumab shortened progression-free and overall survival. BRAF mutation was prognostic, not predictive. PRIME is why extended RAS testing, not KRAS exon 2 alone, is mandatory before any EGFR antibody.
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.
1,183 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival (RAS wild-type)primary | FOLFOX4 plus panitumumab | - | 26 months | 0.78 (0.62 to 0.99) | 0.04 | link |
| FOLFOX4 | - | 20.2 months | ||||
| Progression-free survival (RAS wild-type) | FOLFOX4 plus panitumumab | - | 10.1 months | 0.72 (0.58 to 0.9) | 0.004 | link |
| FOLFOX4 | - | 7.9 months |
The full inclusion and exclusion criteria are on the registry record. Read 2026-10-07. Recruiting overall does not mean a particular site is open; ask the study team.
ClinicalTrials.gov data courtesy of the US National Library of Medicine.
Shares PARADIGM, CRYSTAL & FIRE-3, RAS wild-type (extended KRAS and NRAS testing), Sidedness (left vs right colon).
Shares PARADIGM, CRYSTAL & FIRE-3, Sidedness (left vs right colon), Panitumumab.
Shares PARADIGM, NRAS, Sidedness (left vs right colon), Panitumumab.
Shares PARADIGM, Sidedness (left vs right colon), Panitumumab, BRAF.
Shares PARADIGM, NRAS, Sidedness (left vs right colon), EGFR.
Shares PARADIGM, CRYSTAL & FIRE-3, NRAS, RAS wild-type (extended KRAS and NRAS testing).
Shares NRAS, Panitumumab, BRAF, EGFR.
Shares Sidedness (left vs right colon), Panitumumab, Cetuximab, BRAF.
Every source this page cites, grouped by who published it. Grouping is read from the web address, not assigned by hand.
A source that has moved or gone is reported by the weekly link check. /audit/