Background: PEAK estimated the treatment effect of FOLFOX6 with panitumumab or bevacizumab in first-line wild-type KRAS mCRC. The PRIME study showed significantly improved PFS and OS with panitumumab + FOLFOX vs FOLFOX in patients with wild-type RAS (KRAS/NRAS exon 2, 3, 4) mCRC in a prospective-retrospective analysis (unpublished data).
Methods: This prospective-retrospective analysis of PEAK assessed the effect of panitumumab + FOLFOX6 or bevacizumab + FOLFOX6 on PFS (primary endpoint) and OS in wild-type RAS (KRAS/NRAS exons 2, 3, 4) mCRC. Patients were required to have wild-type KRAS exon 2 tumours. Bidirectional Sanger sequencing and Transgenomic SURVEYOR/WAVE analysis were independently conducted to detect mutations in KRAS exon 3 (codons 59/61), exon 4 (codons 117/146); NRAS exon 2 (codons 12/13), exon 3 (codons 59/61), exon 4 (codons 117/146); BRAF exon 15 (codon 600) in banked specimens.
Results: 285 patients were randomised, 278 received treatment. The current RAS ascertainment rate is 82%. Median PFS in the panitumumab and bevacizumab groups was 13.0 and 10.1 months, respectively. Hazard ratios (HRs) (95%CI) (panitumumab:bevacizumab) for patients with wild-type RAS were 0.66 (0.46–0.95; p=0.03) for PFS and 0.63 (0.39–1.02; p=0.058) for OS; for patients with wild-type KRAS, HR was 0.62 (0.44–0.89); p=0.009) for OS. Median PFS for patients with wild-type KRAS-2, Mutant RAS was 7.8 and 8.9 months in the panitumumab and bevacizumab groups, respectively; HRs were 1.39 (0.73–2.64; p=0.32) for PFS and 0.65 (0.27–1.58) for OS. The incidence of worst grade 3–5 adverse events was consistent with the primary analysis.
Conclusions: In this first-line estimation study in wild-type RAS mCRC, PFS and OS HR favoured panitumumab + FOLFOX6 versus bevacizumab + FOLFOX6, suggesting that activating RAS mutations appear to be predictive for panitumumab treatment effect. The safety profile for both arms was consistent with previously reported studies.