Elucidating the prognostic significance of KRAS, NRAS, BRAF and PIK3CA mutations in Chinese patients with metastatic colorectal cancer. Issue 2 (13th April 2015)

• Record Type: Journal Article
• Authors: Ma, Brigette B; Mo, Frankie; Tong, Joanna H; Wong, Ashley; Wong, SC Cesar; Ho, Wing M; Wu, Cherry; Lam, Polly WY; Chan, KF; Chan, Timothy SK; Tsui, Wilson MS; Tsang, Alex KH; Fung, Mandy NS; Chan, Anthony TC; To, Ka Fai
• Is Part Of: Asia-Pacific journal of clinical oncology. Volume 11:Issue 2(2015:Jun.)
• Page Start: 160
• Page End: 169
• Publication Date: 2015-04-13
• Subjects: Oncology -- Pacific Area -- Periodicals; Cancer -- Treatment -- Pacific Area -- Periodicals; Cancer -- Pacific Area -- Periodicals; Cancer -- Treatment -- Periodicals; 616.9940095
• DOI: 10.1111/ajco.12342
• Languages: English
• ISSNs: 1743-7555

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="ajco12342-sec-0001" sec-type="section"> <title>Aim</title> <p>The prognostic significance of <italic>KRAS</italic>, <italic>NRAS</italic>, <italic>PIK3CA</italic> and <italic>BRAF</italic> mutations was evaluated in Chinese patients with metastatic colorectal cancer (CRC).</p> </sec> <sec id="ajco12342-sec-0002" sec-type="section"> <title>Method</title> <p>Tumor samples from 183 patients were retrospectively tested for <italic>KRAS</italic>, <italic>NRAS</italic>, <italic>PIK3CA</italic> and <italic>BRAF</italic> mutations. Multivariate analysis was performed to determine the relationship between mutational status, drug response and survival.</p> </sec> <sec id="ajco12342-sec-0003" sec-type="section"> <title>Result</title> <p>Over 70% of patients received two or more lines of chemotherapy, 50% had cetuximab and 18% had bevacizumab. The prevalence of <italic>KRAS</italic>, <italic>NRAS</italic>, <italic>BRAF</italic> and <italic>PIK3CA</italic> mutations was 45, 3.2, 5 and 20%, respectively. For the entire cohort, the median overall survival was 24 months (95% confidence interval [CI] = 20.4–26.4 months). Of the genes tested, only <italic>KRAS</italic> mutation was an independent prognostic factor with a multivariate hazard ratio of 1.5 (95% CI = 1.05–2.16, <italic>P</italic> = 0.03). In the subgroup of patients who received cetuximab‐based therapy in the first‐line setting, <italic>KRAS</italic> mutation was associated with a lack of response to chemotherapy (28% <italic>vs</italic> 66%, chi‐square, <italic>P</italic> = 0.01). Patients with <italic>KRAS</italic> mutant tumors (or <italic>KRAS</italic> wild‐type tumors that harbored <italic>BRAF</italic> and/or <italic>PIK3CA</italic> mutations) tended to have lower response rates to chemotherapy and/or cetuximab (<italic>P</italic> = not significant). The number of <italic>NRAS</italic> mutant cases was too small to allow any statistical analysis.</p> </sec> <sec id="ajco12342-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The prevalence of <italic>KRAS</italic>, <italic>NRAS</italic>, <italic>BRAF</italic> and <italic>PIK3CA</italic> mutations in this cohort is consistent with reports from non‐Asian populations, and <italic>KRAS</italic> mutation has both prognostic and predictive significance in Chinese patients with metastatic CRC.</p> </sec> </abstract>