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Open Access Research article

Prognostic value of KRAS genotype in metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to extension of metastatic disease

Gemma Bruera1, Katia Cannita1, Daniela Di Giacomo2, Aude Lamy3, Giancarlo Troncone4, Antonella Dal Mas5, Gino Coletti5, Thierry Frébourg6, Jean Christophe Sabourin7, Mario Tosi6, Corrado Ficorella1 and Enrico Ricevuto1*

Author Affiliations

1 Medical Oncology, S. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy

2 Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy

3 Laboratory of Tumor Genetics, University Hospital, Rouen, France

4 Department of Biomorphologic and Functional Sciences, University Federico II, Napoli, Italy

5 Pathology Department, S. Salvatore Hospital, L'Aquila, Italy

6 INSERM U614, University of Rouen, Rouen, France

7 Department of Pathology, INSERM U614, Rouen University Hospital, Rouen, France

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BMC Medicine 2012, 10:135  doi:10.1186/1741-7015-10-135

Published: 8 November 2012

Abstract

Background

Bevacizumab (BEV) plus triplet chemotherapy can increase efficacy of first-line treatment of metastatic colorectal cancer (MCRC), particularly integrated with secondary liver surgery in liver-limited (L-L) patients. The prognostic value of the KRAS genotype in L-L and other or multiple metastatic (O/MM) MCRC patients treated with the FIr-B/FOx regimen was retrospectively evaluated.

Methods

Tumoral and metastatic samples were screened for KRAS codon 12 and 13 and BRAF mutations by SNaPshot and/or direct sequencing. Fit MCRC patients <75 years were consecutively treated with FIr-B/FOx regimen: weekly 12-h timed flat-infusion/5-fluorouracil (TFI 5-FU) 900 mg/m2, days 1, 2, 8, 9, 15, 16, 22 and 23; irinotecan (CPT-11) 160 mg/m2 plus BEV 5 mg/kg, days 1, 15; oxaliplatin (OXP) 80 mg/m2, days 8, 22; every 4 weeks. MCRC patients were classified as L-L and O/MM. Activity and efficacy were evaluated and compared using log-rank test.

Results

In all, 59 patients were evaluated: 31 KRAS wild-type (53%), 28 KRAS mutant (47%). At 21.5 months median follow-up, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were, respectively: KRAS wild-type 90%, 14 months, 38 months; KRAS mutant 67%, 11 months, 20 months. PFS and OS were not significantly different. PFS and OS were significantly different in L-L compared to O/MM evaluable patients. In KRAS wild-type patients, clinical outcome of 12 L-L compared to 18 O/MM was significantly different: PFS 21 versus 12 months and OS 47 versus 28 months, respectively. In KRAS mutant patients, the clinical outcome of 13 L-L compared to 14 O/MM was not significantly different: PFS 11 months equivalently and OS 39 versus 19 months, respectively.

Conclusions

The KRAS genotype wild-type and mutant does not significantly affect different clinical outcomes for MCRC patients treated with the first-line FIr-B/FOx intensive regimen. KRAS wild-type patients with L-L disease may achieve a significantly prolonged clinical outcome due to integration with secondary liver surgery, with respect to KRAS mutant patients.

Keywords:
disease extension; intensive regimen; KRAS mutations; metastatic colorectal cancer; triplet chemotherapy plus bevacizumab