FOLFIRI and Cetuximab Every Second Week for First-Line Treatment of KRAS Wild-Type Metastatic Colorectal Cancer According to Phosphatase and Tensin Homolog Expression: A Phase II Study

Nicola Personeni, Lorenza Rimassa, Claudio Verusio, Sandro Barni, Luca Rubino, Silvia Bozzarelli, Eugenio Villa, Carlo Carnaghi, Maria Chiara Tronconi, Chiara Gerardi, Francesca Galli, Irene Floriani, Annarita Destro, Carlotta Raschioni, Roberto Labianca, Armando Santoro

Research output: Contribution to journalArticle

Abstract

Abstract Background Retrospective studies have suggested that phosphatase and tensin homolog (PTEN) expression might predict the efficacy of cetuximab in patients with KRAS wild-type metastatic colorectal cancer (mCRC). The present study was designed to prospectively evaluate the efficacy of first-line irinotecan, fluorouracil, and folinate (FOLFIRI) plus cetuximab every second week according to PTEN expression. Patients and Methods Originally, patients with KRAS wild-type mCRC were randomly assigned to receive either FOLFIRI or cetuximab plus FOLFIRI (FOLFIRI-C). After a protocol amendment, the FOLFIRI arm was discontinued, and additional patients received FOLFIRI-C. Cox proportional hazard models were used to investigate the effect of PTEN and MET expression and BRAF and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α mutations on progression-free survival (PFS) and overall survival (OS). Results A total of 35 and 54 patients received FOLFIRI and FOLFIRI-C, respectively. For the patients assigned to FOLFIRI and FOLFIRI-C, the median OS was 17.7 and 23.3 months and the median PFS was 8.2 and 6.6 months, respectively. For patients receiving FOLFIRI-C, the loss of PTEN expression did not affect PFS or OS. Significant interactions for PFS were detected between the MET expression levels (P =.047) and BRAF mutation (P = .018) and treatment. On univariate analysis, BRAF mutation was significantly associated with shorter OS for patients receiving either FOLFIRI-C (P =.016) or FOLFIRI (P =.035). Multivariate analysis confirmed the independent prognostic value of BRAF mutation on OS and that of MET expression levels on PFS (P =.025) and OS (P =.028) but only in the patients receiving FOLFIRI alone. Adverse events with FOLFIRI-C were consistent with those expected from FOLFIRI plus weekly cetuximab. Conclusion Although prospective analysis of PTEN did not allow a validation of the prognostic value of this biomarker, an every second week cetuximab schedule, in addition to first-line FOLFIRI, was effective and well tolerated. The possible predictive value of MET expression levels warrants additional investigation.

Original languageEnglish
Article number197
Pages (from-to)162-169
Number of pages8
JournalClinical Colorectal Cancer
Volume14
Issue number3
DOIs
Publication statusPublished - Sep 1 2015

Keywords

  • Anti-EGFR antibody
  • BRAF
  • MET
  • Phosphatase and tensin homolog
  • PIK3CA

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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