P-0194 - KRAS genotype and the prevalent c.35 G > A mutation affect significantly worse prognosis of metastatic colorectal cancer (MCRC) patients fitting for...

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Biomarkers
Colon Cancer
Rectal Cancer
Presenter Gemma Bruera
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors G. Bruera1, K. Cannita2, A. Tessitore3, A. Cortellini4, C. Sabourin Jean5, M. Tosi6, T. Frébourg6, E. Alesse3, C. Ficorella1, E. Ricevuto1
  • 1Medical Oncology, S. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila/IT
  • 2Medical Oncology, S. Salvatore Hospital, University of L'Aquila, L'Aquila/IT
  • 3Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila/IT
  • 4Medical Oncology, S. Salvatore Hospital, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila/IT
  • 5Department of Pathology, INSERM U614, Rouen University Hospital, Rouen/FR
  • 6INSERM U614, University of Rouen, Rouen/FR

Abstract

Introduction

Bevacizumab (BEV) addiction to chemotherapy can predict increased efficacy in KRAS wild-type and mutant MCRC patients. Codon 12 KRAS mutations differentially affect GTPase function, and confer worse clinical behaviour. Prognostic relevance of KRAS genotype and the prevalent c.35 G > A mutation were verified in patients fit for, and after progression to first line FIr-B/FOx.

Methods

KRAS codon 12/13 mutations were screened. Activity and efficacy were evaluated and compared by log-rank.

Results

Sixty-nine patients (45% overall MCRC) were treated with FIr-B/FOx: 32 KRAS wild-type, 17 c.35 G > A mutant, 20 other mutant. At median follow-up 24 months, objective response rate (ORR) was 77%, progression-free survival (PFS) 13 months, overall survival (OS) 31 months. Among wild-type and mutant patients, respectively: ORR 91% and 64%, PFS 14 and 11 months, OS 38 and 20 months. KRAS mutant patients showed a significantly worse OS compared to wild-type (P = 0.031). c.35 G > A mutant confirmed significantly worse OS compared to wild-type and to wild-type plus other mutant patients. Post-progression to FIr-B/FOx, among 46 second line treated patients (67%), at median follow-up 13 months, ORR was 36%, PFS 8 months, OS 14 months. Among patients treated with re-challenge of triplet chemotherapy plus targeted agent, and triplet regimens, respectively: ORR 83% and 29%, PFS 11 and 8 months, OS 40 and 11 months. OS was significantly different in patients treated with triplet chemotherapy plus targeted agent compared to other treatments, and to triplet regimens. Among wild-type and mutant patients, respectively: ORR 48% and 25%, PFS 9 and 8 months, OS 23 and 12 months. KRAS wild-type compared with mutant patients did not show significantly different OS, while it was significantly worse in c.35 G > A mutant patients.

Conclusion

KRAS mutant genotype and specifically the prevalent c.35 G > A mutation may significantly affect worse clinical outcome in patients fit for first line FIr-B/FOx intensive regimen. c.35 G > A mutation may also significantly affect worse OS after progression.