Analysis of efficacy and prognostic factors in second-line chemotherapy for BRAF V600E mutant metastatic colorectal cancer

Background:BRAF V600E mutant (MT) metastatic colorectal cancer (mCRC) has distinct clinicopatholigical features and extremely poor prognosis. First-line chemotherapy was studied in reports assessing cytotoxic doublets or triplets with or without antibodies, but treatment outcomes of second-line chemotherapy were still unknown. The aim of this study is to examine the efficacy of second-line chemotherapy and evaluate prognostic factors in BRAF V600E MT patients (pts). Methods: We retrospectively reviewed BRAF V600E MT mCRC pts who underwent second-line chemotherapy between 2007 and 2016. BRAF status was examined by PCR-based assay. Results: Of 71 BRAF V600E MT pts, 51 received second-line chemotherapy. Before second-line chemotherapy, baseline patient characteristics were as follows: median age (range), 59 (28–86) years; male/female, 20/31; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0/1/≥2, 17/28/6; histology low, intermediate/high grade or mucinous status, 34/17; primary tumor location right/left side, 29/22; metastatic site liver/peritoneum, 29/35; metastatic sites 1/≥2, 11/40; and Glasgow Prognostic Scale (GPS) 0/1/2, 23/14/12. As first-line chemotherapy, 48 pts (94%) received oxaliplatin- or irinotecan-based regimens, including 5 (10%) who received FOLFOXIRI. In second-line chemotherapy, 39 pts (76%) received oxaliplatin- or irinotecan-based regimens. Median progression-free survival (PFS) and overall survival (OS) were 2.5 and 6.2 months (M). Overall response and disease control rates were 7% and 43%. All regimens achieving partial responses were BRAF inhibitors in combination with anti-EGFR bodies. Therefore, response rate was 0% if 4 pts treated with trial drugs were excluded. Multivariate analyses for both PFS and OS showed that GPS was an independent prognostic factor. Median OS in pts with GPS 0, 1, and 2 was 10.0, 5.0, and 1.6 M, respectively. Conclusions: We revealed the dismal results of second-line chemotherapy in BRAF V600E MT mCRC pts. GPS can predict the treatment outcomes and identify pts unfit for chemotherapy, indicating that GPS is useful in future clinical trials targeting BRAF V600E mutation. Legal entity responsible for the study: Aichi Prefecture Funding: None Disclosure: K. Muro: Research funding from MSD, Daiichi Sankyo, Ono, Kyowa Hakko Kirin, Shionogi, and Gilead Sciences. Honoraria for lectures from Chugai, Takeda, Eli Lilly, Merck Serono, Taiho, and Yakult honsha. All other authors have declared no conflicts of interest.