Association between BRAF mutant classification and the efficacy of pemetrexed-based chemotherapy in Chinese advanced non-small cell lung cancer patients: a multicenter retrospective study

Background: BRAF mutation plays a rare but aggressive oncogenic role in non-small cell lung cancer (NSCLC) patients. The controversy of first-line chemotherapy in patients with different BRAF mutations exists. Here, we identified 41 stage IIIB/IV NSCLC patients with BRAF mutation from 3,669 NSCLC patients by next-generation sequencing (NGS) testing of ctDNA in plasma or tumor tissues. Methods: Kaplan-Meier survival curves were used to compare the prognostic difference of progression-free survival (PFS) and overall survival (OS) in different classes of BRAF mutations. Multivariate Cox proportional-hazards regression was used to determine the hazard ratio (HR) of different prognostic factors in survival. Results: A total of 40 stage IIIB/IV NSCLC patients with BRAF mutation were further divided into four groups according to the updated functional classification of BRAF mutations, 56.1% (23/41) of class 1, 12.2% (5/41) of class 2, 12.2% (5/41) of class 3 and 19.5% (8/41) of others. The median PFS of patients after first-line pemetrexed-based chemotherapy was longer than other regimens of chemotherapy (7.0 vs. 4.0 months, P<0.001). The patients with class 1 BRAF mutation treated with pemetrexed-based first-line chemotherapy had a better OS than other regimens of chemotherapy (30 vs. 22 months, P<0.001). A significant improvement of OS was observed in patients with class 1 BRAF mutation than other groups (25 vs. 12, 15 and 14 months, P<0.0001). Multivariate analysis showed that first-line pemetrexed-based chemotherapy was associated with better PFS and OS (HR =0.16 and 0.31, respectively; P<0.001 and 0.02, respectively), as well as improved OS in patients with class 1 BRAF mutation than other classes (HR =2.15, P<0.001). Conclusions: Pemetrexed-based regimen could be considered as first-line chemotherapy in advanced NSCLC patients with BRAF mutants when target therapy is unavailable, especially in patients harboring class 1 mutations compared with other classes.