P-0236 - The PRIME study: Survival outcomes for patients with RAS/BRAF wild-type metastatic colorectal cancer, by baseline ECOG performance status

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Biomarkers
Colon Cancer
Rectal Cancer
Presenter Marc Peeters
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors M. Peeters1, S. Siena2, J. Douillard3, R. Koukakis4, J. Terwey5, R. Sidhu6
  • 1Antwerp University Hospital, Edegem/BE
  • 2Oncologia Falck e Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milano/IT
  • 3ICO R. Gauducheau, Nantes/FR
  • 4Amgen Ltd, Uxbridge/UK
  • 5Amgen (Europe) GmbH, Zug/CH
  • 6Amgen Inc., Thousand Oaks/US

Abstract

Introduction

In the first-line PRIME study, panitumumab + FOLFOX4 improved overall survival (OS) for patients with KRAS/NRAS (RAS) wild-type (WT) metastatic colorectal cancer (mCRC) vs FOLFOX4 alone (Douillard et al, NEJM 2013). Prespecified subgroup analysis identified only Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 as a negative predictive factor for panitumumab efficacy, although BRAF mutant (MT) status was a strong negative prognostic factor. Here, we further assess the benefit:risk profile of panitumumab in patients with ECOG PS 0/1 RAS/BRAF WT mCRC.

Methods

PRIME was a randomized (1:1) phase III first-line mCRC study comparing the efficacy and safety of panitumumab 6.0 mg/kg Q2W + FOLFOX4 vs FOLFOX4 alone. This exploratory analysis, conducted when ≥80% of patients had an OS event, included patients with RAS/BRAF WT (KRAS/NRAS exons 2-4 [including codon 59] and BRAF exon 15 assessed) mCRC. Median progression-free (PFS) and OS were estimated by baseline ECOG PS (stratification factor). Data were summarised descriptively and tested for significance using Cox's proportional hazards models.

Results

Baseline ECOG PS data were available for 438 of the 439 patients with RAS/BRAF WT mCRC (panitumumab + FOLFOX4 n = 222; FOLFOX4 n = 216). Treatment groups were well balanced with respect to baseline sex, age and metastatic sites. Median PFS (12.3 vs 9.3 months; hazard ratio [HR]: 0.69 [95% confidence interval {CI}: 0.56-0.86]; p < 0.001) and OS (29.7 vs 23.1 months; HR: 0.71 [95% CI: 0.57-0.88]; p = 0.002) were longer in ECOG PS 0/1 RAS/BRAF WT mCRC patients (n = 411) receiving panitumumab + FOLFOX4 vs FOLFOX4. Corresponding PFS (6.4 vs 7.6 months; HR: 0.94 [95% CI: 0.38-2.31]; p = 0.891) and OS (7.6 vs 8.9 months; HR: 0.95 [95% CI: 0.41-2.21]; p = 0.904) values were numerically shorter in ECOG PS 2 patients (n = 27) receiving panitumumab + FOLFOX4 vs FOLFOX4. Among RAS WT/BRAF MT patients, 49 were ECOG PS 0/1 at baseline (panitumumab + FOLFOX4 vs FOLFOX4 median PFS 6.7 vs 5.4 months, p = NS and OS 11.1 vs 9.1 months; p = NS); only 4 patients were ECOG PS 2.

Conclusion

This post-hoc analysis from PRIME suggests that the PFS and OS benefits observed in patients with RAS/BRAF WT mCRC receiving panitumumab + FOLFOX4 are primarily confined to those patients with abaseline ECOG PS of 0/1.