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Open Access Research article

Worse prognosis of KRAS c.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)

Gemma Bruera12, Katia Cannita1, Daniela Di Giacomo2, Aude Lamy3, Thierry Frébourg4, Jean Christophe Sabourin5, Mario Tosi4, Edoardo Alesse2, Corrado Ficorella12 and Enrico Ricevuto12*

Author affiliations

1 Medical Oncology, S. Salvatore Hospital, University of L'Aquila, Via Vetoio, L'Aquila, 67100, Italy

2 Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, L'Aquila, 67100, Italy

3 Laboratory of Tumor Genetics, University Hospital, 1 rue de Germont, 76031 Rouen, France

4 INSERM U614, University of Rouen, 22 Boulevard Gambetta, 76183 Rouen, France

5 Department of Pathology, INSERM U614, Rouen University Hospital, 1 rue de Germont, 76031 Rouen, France

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Citation and License

BMC Medicine 2013, 11:59  doi:10.1186/1741-7015-11-59

Published: 4 March 2013

Abstract

Background

Prognosis of KRAS wild-type and mutant metastatic colorectal cancer (MCRC) patients (pts) treated with bevacizumab (BEV)-containing chemotherapy is not significantly different. Since specific KRAS mutations confer different aggressive behaviors, the prognostic role of prevalent KRAS mutations was retrospectively evaluated in MCRC pts treated with first line FIr-B/FOx, associating BEV to triplet chemotherapy.

Methods

Tumor samples were screened for KRAS codon 12, 13 and BRAF V600E mutations by SNaPshot and/or direct sequencing. MCRC pts <75-years-old were consecutively treated with FIr-B/FOx: weekly 12 hour-timed-flat-infusion/5-fluorouracil (900 mg/m2 on days 1,2, 8, 9, 15, 16,22, 23), irinotecan plus BEV (160 mg/m2 and 5 mg/kg, respectively, on days 1,15); and oxaliplatin (80 mg/m2, on days 8,22). Pts were classified as liver-limited (L-L) and other/multiple metastatic (O/MM). Progression-free survival (PFS) and overall survival (OS) were compared using the log-rank test.

Results

Fifty-nine pts were evaluated at a median follow-up of 21.5 months. KRAS mutant pts: c.35 G > A, 15 (25.4%); c.35 G > T, 7 (11.8%); c.38 G > A, 3 (5%); other, 3 (5%). KRAS wild-type, 31 pts (52.7%). The objective response rate (ORR), PFS and OS were, respectively: c.35 G > A mutant, 71%, 9 months, 14 months; other than c.35 G > A mutants, 61%, 12 months, 39 months. OS was significantly worse in c.35 G > A pts compared to KRAS wild-type (P = 0.002), KRAS/BRAF wild-type (P = 0.03), other MCRC patients (P = 0.002), other than c.35 G > A (P = 0.05), other codon 12 (P = 0.03) mutant pts. OS was not significantly different compared to c.35 G > T KRAS mutant (P = 0.142).

Conclusions

KRAS c.35 G > A mutant status may be significantly associated with a worse prognosis of MCRC pts treated with first line FIr-B/FOx intensive regimen compared to KRAS/BRAF wild type and other than c.35 G > A mutant pts.

Keywords:
KRAS mutation; Kras c.35 G > A mutation; triplet chemotherapy plus bevacizumab; metastatic colorectal cancer; FIr-B/FOx