Real-world outcomes of targeted therapies and local interventions in BRAF V600E–mutated metastatic colorectal cancer: A single-center retrospective study.

Abstract

203 Background: Metastatic colorectal cancer (mCRC) patients with BRAF V600E mutations, especially those with microsatellite stable (MSS) tumors, have poor prognoses. Chemotherapy has limited efficacy in this subgroup, especially for second-line or subsequent-line treatments. Current research is increasingly focusing on the integration of targeted therapies and local interventions, but real-world evidence remains scarce, particularly from Asian cohorts. This study leverages real-world data to evaluate the impact of novel therapeutic combinations, including triplet and doublet targeted therapies, alongside local treatments in this high-risk patient population. Methods: This retrospective study includes MSS-type mCRC patients with BRAF V600E mutations treated at the Sixth Affiliated Hospital of Sun Yat-sen University between April 2014 and May 2024. Patients receiving targeted therapies were stratified into three groups: Triplet group (BRAF, EGFR, and MEK inhibitors, including Dabrafenib, Cetuximab and Trametinib), Doublet group (BRAF and EGFR inhibitors, including Dabrafenib and Cetuximab or Encorafenib and Cetuximab), and Doublet target-chemotherapy group (BRAF and EGFR inhibitors combined with chemotherapy, including Vemurafenib, Irinotecan, and Cetuximab). Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and objective response rate (ORR). Results: Among 239 enrolled patients, 58 received targeted therapy and 68 underwent conventional chemotherapy as second-line treatment. 63.5% (80/126) of these patients underwent local interventions, including primary tumor resection, metastasectomy, CRS±HIPEC, and liver ablation. Targeted therapy demonstrated significantly improved mPFS compared to conventional chemotherapy (5.5 vs. 4.2 months, HR = 0.44; 95% CI: 0.29-0.68, p < 0.001). OS did not differ significantly between the two treatment arms (12.7 vs. 12.1 months, HR = 0.80; 95% CI: 0.50-1.25, p = 0.330). In the triplet group, ORR, mPFS, and mOS were 21%, 5.8 months and 18.0 months, respectively, showing a trend towards enhanced efficacy compared to the other targeted therapy groups, albeit without statistical significance. Patients who received targeted therapy (n=35) or chemotherapy (n=45) in combination with local interventions demonstrated significantly prolonged OS compared to those without local therapy (mOS: 22.3 vs. 9.6 months; HR = 0.19; 95% CI: 0.09-0.42; p < 0.001 and 14.3 vs. 10.9 months; HR = 0.53; 95% CI: 0.29-0.98; p = 0.042, respectively). Conclusions: Optimal treatment for BRAF V600E mCRC remains under investigation. This study suggests that combining targeted therapies with selective local interventions may significantly improve patient survival in this challenging subgroup, warranting further prospective evaluation.