Prevalence, genetic variations and clinical outcomes of BRAF-V600 mutated advanced NSCLC in China: a retrospective real-world multi-centre study.

Abstract

Background: Due to the low incidence of BRAF mutations, limited data is available about their prevalence and clinical characteristics. Moreover, comparative real-world efficacy of dabrafenib combined with trametinib versus other treatment regimens, especially in Chinese patients, is also lacking.

Methods: Patients who had BRAF genetic testing from the Lung Cancer Big Data Precise Treatment Collaboration Group (LANDSCAPE) database were included as Cohort I. The LANDSCAPE database comprises next-generation sequencing (NGS) data of 175,336 patients with lung cancer, originating from 6 Chinese genetic testing institutions. Cohort II included patients with unresectable locally advanced or metastatic NSCLC with a primary BRAF mutation from 19 centres in China from December 2015 to September 2022.

Findings: In Cohort I, of patients with NSCLC, 6249 (3.56%, 95% CI: 3.48%-3.65%) were confirmed to harbour a BRAF mutation. BRAF V600E accounted for 24.6% (1539/6249) of all patients with BRAF-mutated NSCLC. In Cohort II, a total of 129 patients with locally advanced or metastatic BRAF-mutated NSCLC were included. Of 112 patients who received NGS testing, 80 (71.4%) patients had concomitant mutations. The median first-line real-world progression-free survival (rwPFS) of dabrafenib plus trametinib for patients with BRAF V600 mutations was 25.0 months (N = 37), which was numerically longer than first-line immunotherapy-based therapy (N = 12, 15.7 months), and chemotherapy (N = 17, 9.2 months).

Interpretation: This study indicates that dabrafenib plus trametinib could be considered as the optimal treatment option for Chinese patients with NSCLC harbouring BRAF V600 mutations.

Funding: National Natural Science Foundation of China (82072583); Beijing Municipal Administration of Hospitals Incubating Program (PX2020044); Beijing Hospitals Authority Youth Programme (QML20231113); Science Foundation of Peking University Cancer Hospital (2022-17); Peking University Cancer Hospital Inner Mongolia Hospital Public Hospital Reform and High-Quality Development Demonstration Project (Gastrointestinal Cancer + Thoracic Cancer) Research Fund (2024YNYB006).