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BMC Medicine
Published in: BMC Medicine 1/2013

Open Access 01-12-2013 | Research article

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

Authors: Gemma Bruera, Katia Cannita, Daniela Di Giacomo, Aude Lamy, Thierry Frébourg, Jean Christophe Sabourin, Mario Tosi, Edoardo Alesse, Corrado Ficorella, Enrico Ricevuto

Published in: BMC Medicine | Issue 1/2013

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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.
Appendix
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Metadata
Title
Worse prognosis of KRASc.35 G > A mutant metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx)
Authors
Gemma Bruera
Katia Cannita
Daniela Di Giacomo
Aude Lamy
Thierry Frébourg
Jean Christophe Sabourin
Mario Tosi
Edoardo Alesse
Corrado Ficorella
Enrico Ricevuto
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2013
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-11-59

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