Braf-mutant metastatic non-small-cell lung cancer: Real world data from the Italian biomarker atlas database

Background: BRAF mutations identify a small subgroup of patients (pts) with non-small cell lung cancer (NSCLC). Dabrafenib/trametinib (D/T) combination is associated with high response rates and durable anti-tumor activity in BRAF-V600-mutants. Several open questions still remain unanswered in clinical practice, including the efficacy of treatments based on clinical and molecular characteristics, the activity in patients with brain metastases, the optimal sequence with immunotherapy-based therapies. Here we present outcomes among advanced BRAF-mutant NSCLC patients from the Italian ATLAS registry. Methods: Patients with metastatic BRAF-mutated NSCLC were included. Clinical-pathological features, treatment effectiveness and safety outcomes were retrospectively collected from the Italian real-world ATLAS registry. Results: A total of 244 BRAF-mutated NSCLC pts were enrolled, including 70 % V600E mutations. The median PFS of first line D/T was 19.8 months (95 % CI: 10.7-29.0), with a 2-year OS rate of 65.4 % and a PFS2 of 6.6 months (95 % CI: 0-14.3). The activity of D/T differs among sex (mPFS was 13.6 mos and 25.3 mos and 2-yr OS rate were 54.9 % and 72.3 % in males and females, respectively) and smoking status (mPFS was 18.4 mos, 25.6 mos and 24 mos in never, former and current smokers, respectively). Concomitant MET amplification was associated with a shorter median PFS (mPFS was 13.6 mos vs. 44.3 mos with and without MET amplification respectively) in pts treated with D/T as 1st line. Conclusions: These data confirm the efficacy and safety of first line D/T in BRAF V600E-mutated pts in the real-world setting consistently with prior studies, suggesting a differential activity among key clinical-molecular subgroups.