Clinicopathologic features and treatment efficacy of Chinese patients with BRAF-mutated metastatic colorectal cancer: a retrospective observational study

摘要

Background: The prognostic role of the V600 E mutation of v-raf murine sarcoma viral oncogene homolog B1(BRAF)in metastatic colorectal cancer(mCRC) is well established, but the therapeutic regimen targeting this disease is lacking. This study aimed to analyze the clinicopathologic features of and treatment efficacy of commonly used regimens on BRAF-mutated mCRCs.Methods: We collected and reviewed the medical records of mCRC patients treated at Peking University Cancer Hospital & Institute(Beijing, China) between July 2011 and July 2016. Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS), and BRAF mutational status was assayed using direct sequencing. The details of clinicopathologic characteristics of patients and their responses to FOLFOXIRI regimen or standard therapy were obtained by reviewing the medical records. The progression-free survival(PFS) and overall survival(OS)were assessed using Kaplan-Meier analysis and compared using the log-rank test.Results: Of 1694 patients studied, 75 had BRAF exon 15 mutations. Of these 75 patients, 71 had V600 E mutation, 1 had D594 G mutation, 2 had K601 E mutation, and 1 had a novel T599_V600 insAGA alteration. No patients had KRAS or NRAS mutations. Of 63 patients with BRAFV600 E-mutated mCRC and sufficient clinical data, 27(42.9%) had right-sided colon tumors, 19(30.2%) had left-sided colon tumors, and 17(26.9%) had rectal tumors; 26(41.3%) had peritoneal metastases, and 50(79.4%) had distant lymph node metastases.The patients with BRAF K601 E-and T599_V600 insAGA-mutated tumors had similar clinicopathologic features to those with BRAFV600 E-mutated tumors. Patients with the BRAFV600 E mutation benefited more from FOLFOXIRI regimen compared with patients who underwent standard therapy(overall response rate 83.3% vs. 14.0%; median PFS 6.4 months vs. 2.8 months, P = 0.220; median OS11.0 months vs. 6.9 months, P = 0.048).Conclusions: BRAFV600 E mutations were commonly identified in right-sided tumors and showed a high incidence of peritoneal and distant lymph nodes metastases.This subtype of mCRC was characterized by short OS and unique patterns of metastasis. Compared with standard treatment regimens, the FOLFOXIRI regimen had acceptable and manageable toxicities and favorable efficacy on patients with BRAF-mutated mCRC.