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

• Published in: BMC cancer 2017-01, Vol.17 (1), p.38-38, Article 38
• Main Authors: Nakayama, Izuma, Shinozaki, Eiji, Matsushima, Tomohiro, Wakatsuki, Takeru, Ogura, Mariko, Ichimura, Takashi, Ozaka, Masato, Takahari, Daisuke, Suenaga, Mitsukuni, Chin, Keisho, Mizunuma, Nobuyuki, Yamaguchi, Kensei
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Angiogenesis Inhibitors - therapeutic use; Bevacizumab; Bevacizumab - therapeutic use; Biomarkers; Biomarkers, Tumor - genetics; Cancer therapies; Care and treatment; Chemotherapy; Class I Phosphatidylinositol 3-Kinases - genetics; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Combination drug therapy; Development and progression; Dosage and administration; Female; Follow-Up Studies; Gene mutation; Genetic aspects; Health aspects; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Liver Neoplasms - secondary; Lymphatic Metastasis; Male; Metastasis; Middle Aged; Mutation; Mutation - genetics; Neoplasm Staging; Patients; Prognosis; Proto-Oncogene Proteins B-raf - genetics; ras Proteins - genetics; Retrospective Studies; Survival Rate; Tomography; Tumors
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-016-2994-6

After 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. Of 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. The 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. Patient 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.