Outcomes of BRAF, MET, RET, and ROS1 Mutated Non-Small Cell Lung Cancer With Brain Metastases (NSCLCBM)

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) also accounts for the highest number of brain metastases. Recent advances have been made from standard platinum-based chemotherapy to gene-directed therapies. EGFR and ALK mutations are the most well-studied directed therapies. However, newer targets in NSCLC are being studied, including BRAF mutations, MET exon skipping, RET fusions, and ROS1 rearrangements. In this retrospective study, we evaluated overall survival (OS) and progression-free survival (PFS) in NSCLCBM patients with BRAF, MET, RET, and ROS1 gene mutations.NSCLCBM patients diagnosed between 2010 and 2019 at our tertiary care center were investigated. Molecular marker status, systemic therapies, and date of progression were collected for each patient. We defined OS as the date of diagnosis of brain metastases to the date of last follow-up or death. The Cox proportional model was used to estimate OS and PFS.2989 NSCLCBM patients were detected, 18 had a BRAF mutant, 12 had MET exon skipping, 4 had RET fusion, and 6 had ROS1 rearrangement. The median OS (mOS) in patients who were BRAF positive was 101.7 months, ALK positive was 97.7 months, RET positive was 49.3 months, and ROS1 positive was 50.8 months. The median PFS (mPFS) for BRAF, MET, RET, and ROS1 was 99.2 months, 97.7 months, 31.6 months, and 40.6 months, respectively.Molecular mutations continue to be a topic of great interest in the field of NSCLCBM. These molecular mutations function as both prognostic predictors and druggable targets. Our retrospective study showed improved mPFS in patients with BRAF and MET mutations when compared to RET and ROS mutated patients and improved mOS in patients with MET mutations when compared to patients with RET mutations. However, due to the small sample size and the fact that these mutations are not mutually exclusive, it is difficult to determine statistical significance. Further studies need to be completed with larger sample sizes to determine outcomes in isolated mutations.