Investigating clinical and molecular characteristics of BRAF mutated MSS CRC and impact of inflammatory markers on survival outcomes.

Abstract

e15595 Background: Approximately 8% of patients with MSS metastatic colorectal cancer (mCRC) have BRAF mutation, which is typically associated with worse prognosis. In this study, we investigated clinical and molecular features of BRAF mutated mCRC including systemic inflammatory markers and examined their impact on prognosis. Methods: A total of 70 patients (pts) with BRAF mutated microsatellite stable colon cancer were identified from 2014-2022 using our institutional molecular database. Patients with no evidence of distant metastatic disease were excluded, with 53 patients finally analysed. Neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) at diagnosis were calculated as simple ratios of neutrophils to lymphocytes and platelets to lymphocytes, respectively, as inflammatory biomarkers. Time to next treatment was defined as the time between initiation of first line and second line treatments. Kaplan Meier analysis and cox proportional hazard models were used to analyze survival data. Results: Nearly half of the pts (45%) were diagnosed with de novo metastatic disease. Around 70% of the pts had class I BRAF (V600E) mutation. Pts were predominantly treated with FOLFOX, and only 3 pts received FOLFIRINOX/FOLFOXIRI in the first line setting for metastatic colon cancer. Only 12/29 (41%) patients with BRAF V600E mutation received BRAF targeting agents. Notably, 44% underwent metastasis-directed local treatments, including CRS+ HIPEC, metastatectomy, and liver ablation. PS at diagnosis showed significant association with overall survival (p=0.001), however, due to small sample size with PS 2 and 3, the reliability of this finding is limited. Interestingly, NLR was associated with shorter time from first to second line treatment (p = 0.012). This association remained significant in multivariate analyses (p=0.024). This relation was not seen for OS outcomes. Conclusions: In this single-center retrospective analysis, we noted that patients with BRAF V600E more likely to present with de novo metastatic disease and less than half the pts with BRAF V600E mutation received BRAF targeting agent supporting the use of these agents in the first line based on recent data from the BREAKWATER trial Additionally, NLR at diagnosis is an important prognostic marker associated with a shorter time to next treatment, indicative of poor response to first-line therapy. Baseline characteristics. Characteristic N = 53 1 Median age at initial dx 67.00 (41.00 - 91.00) Gender Female 30 (57%) Male 23 (43%) Ethnicity African American 2 (3.8%) White 51 (96%) Initial Stage Group I 2 (3.8%) II 11 (21%) III 16 (30%) IV 24 (45%) Right vs left Unknown 1 (1.9%) Left 10 (19%) Right 42 (79%) Liver mets N 19 (36%) Y 24 (45%) Unknown 10 (19%) Number of sites of met 1 20 (38%) 2 17 (32%) 3 5 (9.4%) 4 1 (1.9%) Unknown 10 (19%) PS at diagnosis 0 37 (70%) 1 12 (23%) 2 3 (5.7%) 3 1 (1.9%) TMB (Muts/Mb) 7.86 (0.00 - 73.64)