PD-0004 - The PRIME study: Survival outcomes in patients with KRAS/NRAS wild-type metastatic colorectal cancer and non-liver-limited disease

Date 27 June 2014
Event World GI 2014
Session Poster discussion session 1 – EGFR-targeted agents
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Colon Cancer
Rectal Cancer
Presenter Jean-Yves Douillard
Citation Annals of Oncology (2014) 25 (suppl_2): ii5-ii13. 10.1093/annonc/mdu164
Authors S. Salvatore
  • Oncologia Falck e Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milano/IT

Abstract

Introduction

European Society for Medical Oncology guidelines recommend first-line treatment with an active combination regimen for patients with metastatic colorectal cancer (mCRC) and multiple metastases as well as those with more limited disease (Schmoll et al, Ann Oncol 2012). Panitumumab + FOLFOX4 is an active regimen that improved overall survival (OS) vs FOLFOX4 alone in the first-line treatment of patients with KRAS/NRAS (RAS) WT mCRC (PRIME study). In this exploratory analysis of PRIME, we report the efficacy of panitumumab + FOLFOX4 vs FOLFOX4 in mCRC patients whose metastatic disease was not limited to the liver (non-LLD).

Methods

PRIME was a randomized (1:1) phase III study comparing the efficacy and safety of first-line panitumumab 6.0 mg/kg Q2W + FOLFOX4 vs FOLFOX4 in patients with mCRC. In this exploratory analysis conducted when ≥80% of patients had an OS event, median progression-free (PFS) and OS were estimated for patients with RAS WT (KRAS/NRAS exons 2-4 assessed, including codon 59) non-LLD. 3-year OS rates were also evaluated. Data were summarised descriptively and tested for significance using Cox's proportional hazards models.

Results

Of the 505 patients with RAS WT mCRC, 416 had non-LLD (panitumumab + FOLFOX4 n = 205; FOLFOX4 n = 211). Treatment arms were well balanced with respect to baseline sex, age and metastatic sites. Overall, 82% of patients had liver involvement at baseline, 51% had ≥3 metastatic sites (median 3 [range 1-6]) and median lactate dehydrogenase levels were 373 (range 4-5780) U/L. Median PFS (11.1 vs 8.0 months; hazard ratio [HR]: 0.73 [95% confidence interval {CI}: 0.60-0.90]; p = 0.0027) and OS (23.8 vs 18.4 months; HR: 0.78 [95% CI: 0.63-0.96]; p = 0.0185) were longer in RAS WT non-LLD patients receiving panitumumab + FOLFOX4 vs FOLFOX4. 3-year OS rates were 31% vs 23% for non-LLD patients receiving panitumumab + FOLFOX4 vs FOLFOX4, respectively. Numeric benefits in PFS (11.3 vs 9.9 months; HR: 0.75 [95% CI: 0.48-1.19]; p = 0.2223) and OS (40.7 vs 33.4 months; HR: 0.71 [95% CI: 0.43-1.16]; p = 0.1737) were also observed in patients with liver-limited disease receiving panitumumab + FOLFOX4 (n = 48) vs FOLFOX4 (n = 41).

Conclusion

This post-hoc analysis from PRIME suggests that the PFS and OS benefits observed with first-line panitumumab + FOLFOX4 vs FOLFOX4 treatment in the overall population are also seen in the subgroups of patients who have non-LLD and LLD.