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

BMC Medicine

Enrico Ricevuto⁵  Corrado Ficorella⁵  Mario Tosi⁴  Jean Christophe Sabourin⁶  Thierry Frébourg⁴  Gino Coletti²  Antonella Dal Mas²  Giancarlo Troncone³  Aude Lamy⁷  Daniela Di Giacomo¹  Katia Cannita⁵  Gemma Bruera⁵ 

[1] Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy;Pathology Department, S. Salvatore Hospital, L'Aquila, Italy;Department of Biomorphologic and Functional Sciences, University Federico II, Napoli, Italy;INSERM U614, University of Rouen, Rouen, France;Medical Oncology, S. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy;Department of Pathology, INSERM U614, Rouen University Hospital, Rouen, France;Laboratory of Tumor Genetics, University Hospital, Rouen, France

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

Others  :  857308
DOI  :  10.1186/1741-7015-10-135

 received in 2012-04-21, accepted in 2012-11-08,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Bruera et al; licensee BioMed Central Ltd.

【 图 表 】

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