Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer

Br J Cancer. 2016 Nov 8;115(10):1215-1222. doi: 10.1038/bjc.2016.343. Epub 2016 Oct 20.

Abstract

Background: To investigate tumour biomarker status and efficacy of first-line panitumumab+FOLFIRI for metastatic colorectal carcinoma (mCRC).

Methods: 154 patients received first-line panitumumab + FOLFIRI every 14 days. Primary end point was objective response rate (ORR). Data were analysed by tumour RAS (KRAS/NRAS) and BRAF status, and baseline amphiregulin (AREG) expression.

Results: Objective responses occurred more frequently in RAS wild type (WT) (59%) vs RAS mutant (MT) (41%) mCRC and in RAS WT/BRAF WT (68%) vs RAS or BRAF MT (37%) disease. Median response duration was longer in RAS WT (13.0 months) vs RAS MT (5.8 months) (hazard ratio (HR): 0.16). Median progression-free survival was longer in RAS WT vs MT (11.2 vs 7.3 months; HR, 0.37) and was also longer in RAS WT/BRAF WT vs RAS or BRAF MT (13.2 vs 6.9 months; HR, 0.25). Incidence of adverse events was similar regardless of RAS/BRAF status, and no new safety signals were noted. Among patients with RAS WT tumours, ORR was 67% with high AREG expression and 38% with low AREG expression.

Conclusions: First-line panitumumab+FOLFIRI was associated with favourable efficacy in patients with RAS WT and RAS WT/BRAF WT vs MT mCRC tumours and was well tolerated.

MeSH terms

  • Amphiregulin / genetics
  • Antibodies, Monoclonal / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Clinical Trials, Phase II as Topic
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Disease-Free Survival
  • Fluorouracil / administration & dosage
  • Humans
  • Kaplan-Meier Estimate
  • Leucovorin / administration & dosage
  • Panitumumab
  • Proportional Hazards Models
  • Proto-Oncogene Proteins B-raf / genetics*
  • Retrospective Studies
  • ras Proteins / genetics*

Substances

  • Amphiregulin
  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Panitumumab
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • ras Proteins
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • IFL protocol