Efficacy of Dabrafenib Plus Trametinib Combination in Patients with BRAF V600E-Mutant NSCLC in Real-World Setting: GFPC 01-2019

SIMPLE SUMMARY: Mutations of the BRAF oncogene are reported in tumors of patients with non-small-cell lung cancer in 2–4% of cases (about half of them are V600E mutation). Dabrafenib plus trametinib combination is approved in Europe for BRAF V600E-mutant metastatic non-small-cell lung cancer. However, there are few published data on the efficacy and safety of this combination outside of formal clinical trials. In this retrospective multicentric observational study, we describe in a real-life setting the characteristics and the outcomes of patients with BRAF V600E-mutant NSCLC treated with the dabrafenib and trametinib combination. The results in 40 patients suggest that efficacy and safety of dabrafenib plus trametinib combination in patients with metastatic non-small-cell lung cancer harboring this mutation are comparable in a real-world setting and in clinical trials for both previously untreated and treated patients. ABSTRACT: Dabrafenib plus trametinib combination is approved in Europe for BRAF V600E-mutant metastatic non-small-cell lung cancer (NSCLC). The objective of this study was to assess efficacy and safety of this combination in a real-world setting. This retrospective multicentric study included 40 patients with advanced NSCLC harboring BRAF V600E mutation and receiving dabrafenib plus trametinib. The median progression-free survival (PFS) and overall survival (OS) were 17.5 (95% CI 7.1–23.0) months and 25.5 (95% CI 16.6–not reached) months in the entire cohort, respectively. For the 9 patients with first-line treatment, median PFS was 16.8 (95% CI 6.1–23.2) months and median OS was 21.8 (95% CI 1.0–not reached) months; for the 31 patients with second-line or more treatments, median PFS and OS were 16.8 (95% CI 6.1–23.2) months and 25.5 (95% CI 16.6–not reached) months, respectively. Adverse events led to permanent discontinuation in 7 (18%) patients, treatment interruption in 8 (20%) and dose reduction in 12 (30%). In conclusion, these results suggest that efficacy and safety of dabrafenib plus trametinib combination in patients with BRAF V600E metastatic NSCLC are comparable in a real-world setting and in clinical trials for both previously untreated and treated patients.