Retrospective study of RAS/PIK3CA/BRAF tumor mutations as predictors of response to first-line chemotherapy with bevacizumab in metastatic colorectal cancer patients

BMC Cancer

Research Article

Takashi Ichimura¹  Daisuke Takahari¹  Masato Ozaka¹  Nobuyuki Mizunuma¹  Tomohiro Matsushima¹  Kensei Yamaguchi¹  Izuma Nakayama¹  Takeru Wakatsuki¹  Keisho Chin¹  Mariko Ogura¹  Mitsukuni Suenaga¹  Eiji Shinozaki¹ 

[1] Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, 135-8550, Tokyo, Japan;

关键词: RAS;    PIK3CA;    BRAF;    Colorectal cancer;    bevacizumab;   

DOI  :  10.1186/s12885-016-2994-6

 received in 2015-12-26, accepted in 2016-12-13,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAfter analysis of minor RAS mutations (KRAS exon 3, 4/NRAS) in the FIRE-3 and PRIME studies, an expanded range of RAS mutations were established as a negative predictive marker for the efficacy of anti-EGFR antibody treatment. BRAF and PIK3CA mutations may be candidate biomarkers for anti-EGFR targeted therapies. However, it remains unknown whether RAS/PIK3CA/BRAF tumor mutations can predict the efficacy of bevacizumab in metastatic colorectal cancer. We assessed whether selection according to RAS/PIK3CA/BRAF mutational status could be beneficial for patients treated with bevacizumab as first-line treatment for metastatic colorectal cancer.MethodsOf the 1001 consecutive colorectal cancer patients examined for RAS, PIK3CA, and BRAF tumor mutations using a multiplex kit (Luminex®), we studied 90 patients who received combination chemotherapy with bevacizumab as first-line treatment for metastatic colorectal cancer. The objective response rate (ORR) and progression-free survival (PFS) were evaluated according to mutational status.ResultsThe ORR was higher among patients with wild-type tumors (64.3%) compared to those with tumors that were only wild type with respect to KRAS exon 2 (54.8%), and the differences in ORR between patients with wild-type and mutant-type tumors were greater when considering only KRAS exon 2 mutations (6.8%) rather than RAS/PIK3CA/BRAF mutations (18.4%). There were no statistically significant differences in ORR or PFS between all wild-type tumors and tumors carrying any of the mutations. Multivariate analysis revealed that liver metastasis and RAS and BRAF mutations were independent negative factors for disease progression after first-line treatment with bevacizumab.ConclusionsPatient selection according to RAS/PIK3CA/BRAF mutations could help select patients who will achieve a better response to bevacizumab treatment. We found no clinical benefit of restricting combination therapy with bevacizumab for metastatic colorectal cancer patients with EGFR-wild type tumors.

【 授权许可】

CC BY   
© The Author(s). 2017