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Testing only the two commonest spots in KRAS was not enough: another one in six patients called wild-type turned out to carry a RAS mutation somewhere else, and they did no better on the antibody than the ones already excluded.
In a prospective-retrospective analysis of the PRIME trial, the efficacy and safety of panitumumab plus FOLFOX4 against FOLFOX4 alone were assessed by RAS (KRAS or NRAS) and BRAF mutation status. A total of 639 patients whose tumours lacked KRAS exon 2 mutations had results for at least one of KRAS exon 3 or 4, NRAS exon 2, 3 or 4, or BRAF exon 15, with 90% overall ascertainment. Among 512 patients with no RAS mutation, progression-free survival was 10.1 months with panitumumab-FOLFOX4 against 7.9 with FOLFOX4 alone (hazard ratio 0.72) and overall survival 26.0 against 20.2 months (hazard ratio 0.78). A total of 108 patients (17%) with non-mutated KRAS exon 2 had other RAS mutations, and those mutations were associated with inferior progression-free and overall survival on panitumumab-FOLFOX4, consistent with the findings in KRAS exon 2 mutants. BRAF mutations were a negative prognostic factor.
It moved the label and every guideline from KRAS exon 2 testing to extended RAS testing of KRAS and NRAS exons 2, 3 and 4, which is the threshold in use today.
Shares KRAS G12D (and other non-G12C KRAS mutations), Wild-type (WT), therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF), RAS / RAF / MEK / ERK (MAPK).
Shares PARADIGM, NRAS, Wild-type (WT), EGFR.
Shares NRAS, Panitumumab, BRAF, EGFR.
Shares Salvatore Siena, Panitumumab, BRAF, RAS / RAF / MEK / ERK (MAPK).
Shares PARADIGM, NRAS, Panitumumab, BRAF.
Shares NRAS, Panitumumab, Next-generation sequencing (NGS), EGFR.
Shares NRAS, Wild-type (WT), Next-generation sequencing (NGS), BRAF.
Shares KRAS G12D (and other non-G12C KRAS mutations), PARADIGM, Wild-type (WT), therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF).