547P - Impact of baseline age on efficacy and safety of first-line panitumumab (pmab) + FOLFOX4 vs FOLFOX4 treatment

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Jean-Yves Douillard
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors J. Douillard1, S. Siena2, M. Peeters3, R. Koukakis4, J. Terwey5, J. Tabernero6
  • 1Medical Oncology, Centre René Gauducheau (ICO) Institut de Cancerologie de l'Ouest, 44805 - ST HERBLAIN/FR
  • 2Niguarda Cancer Center, Ospedale Niguarda Ca’ Granda, 20162 - Milan/IT
  • 3Department Of Oncology, Antwerp University Hospital, 2650 - Edegem/BE
  • 4Biostatistics, Amgen Ltd, UB8 1DH - Uxbridge/GB
  • 5Medical Development - Oncology, Amgen (Europe) GmbH, 6301 - Zug/CH
  • 6Vall D'hebron Institute Of Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES

Abstract

Aim

Data from PRIME showed pmab + FOLFOX4 to be an effective and tolerable first-line treatment for patients (pts) with RAS WT metastatic colorectal cancer (mCRC). However, treatment outcomes can differ in pts of differing age.

Methods

PRIME was a randomised (1:1) phase 3 study comparing first-line pmab 6.0 mg/kg Q2W + FOLFOX4 vs FOLFOX4 in mCRC pts. Pts with no mutations in KRAS/NRAS exons 2, 3 or 4 (including codon 59) were classed as having RAS WT mCRC. In this exploratory analysis conducted when ≥80% of pts had an OS event, efficacy/safety were assessed for RAS WT pts by baseline age (<65, ≥65 and ≤75, >75 years [yr]). Efficacy endpoints assessed were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Data were analysed using Cox's proportional hazards models.

Results

Overall 505 pts had RAS WT mCRC and 499 pts were included in this analysis of age. Median OS and PFS were longer with pmab + FOLFOX4 vs FOLFOX4 in pts <65 yr (OS: 25.8 vs 21.2 months [mo]; PFS: 12.9 vs 8.7 mo) and also in pts ≥65 yr overall (OS: 26.6 vs 17.4 mo; PFS: 9.7 vs 9.2 mo) [Table]. ORRs were higher in the pmab + FOLFOX4 vs FOLFOX4 arm for pts <65 yr (65% vs 47%) and pts ≥65 yr overall (49% vs 42%). Pmab + FOLFOX4-treated pts ≥65- ≤ 75 yr (n = 154) had higher ORRs (57% vs 45%) and longer OS (hazard ratio [HR]: 0.74; 95% confidence intervals [CI]: 0.52-1.05) and PFS (HR: 0.87; 95% CI: 0.62-1.23) than FOLFOX4-treated pts. There were insufficient pts >75 yr (n = 34) to draw conclusions, but OS (HR: 1.16; 95% CI: 0.55-2.45) and PFS (HR: 1.06; 95% CI: 0.50-2.26) appeared similar. No new safety signals were identified in any of the age groups.

Age <65 yr Age ≥65 yr
Pmab + FOLFOX4 FOLFOX4 Pmab + FOLFOX4 FOLFOX4
N 156 155 94 94
ORR % 65 47 53 46
PFS HR 95% CI 0.655 0.516–0.832 0.879 0.648–1.193
OS HR 95% CI 0.748 0.584–0.957 0.797 0.581–1.092

Conclusions

In subgroup analyses of RAS WT pts from PRIME, pmab + FOLFOX4 appears to offer benefit over FOLFOX4 alone both in pts <65 and ≥65 yr. Analysis of efficacy in the >75 yr population was limited by pt numbers and more research is needed to assess treatment benefit in these pts.

Disclosure

J. Douillard: has participated in AMGEN steering committee and symposia (both compensated); S. Siena: has been a member of advisory boards for Amgen, Bayer, Roche, Sanofi-Aventis, and Celgene M. Peeters: has had consultant/advisory roles for Amgen (all compensated) and has also received honoraria and research funding from Amgen; R. Koukakis: is an Amgen Ltd employee and stockholder; J. Terwey: is an Amgen (Europe) GmbH employee and stockholder; J. Tabernero: has participated in Advisory boards for Amgen.