Background: BRAF mutations are found in 2-3% of NSCLC. BRAF inhibitors reportedly have antitumor activity. The French National Cancer Institute (INCa) launched a program giving nationwide access to vemurafenib for cancer patients with BRAF-mutated tumors and supported molecular screening. We herein report the NSCLC cohort results. Method: BRAF mutational status was assessed on INCa molecular genetic centers by direct sequencing or NGS. Patients with mutated BRAF (V600E and others mutations) progressing after 1 standard treatment were proposed vemurafenib 960 mg BID. Objective Response Rate (ORR) was assessed using RECIST v1.1 every 8 weeks. A sequential Bayesian approach was planned to allow early stopping using an inefficacy bound for ORR of 10%. If no early stopping occurred, the treatment was considered worthy for further evaluation if there was a 90% probability that the estimated ORR is 30%, the efficacy bound. Result: From 10/2014 to 10/2017, 118 NSCLC patients were enrolled: 101 with BRAF V600E and 17 with other potentially activating mutations (4 G466, 4 G469, 1 G596, 5 K601, and 3 N581). Median age was 68 years (range 34e85), 71% smokers, 48% females, 100% non-squamous histology, and 20% with ECOG PS 2. Most frequent grade 3 adverse events (AEs) were asthenia (9% of patients), epidermoid carcinoma (6%), dermatitis (5%), and increased GGT (5%). Three toxic deaths were reported: 1 nausea and vomiting leading to dehydration, 1 pneumonia, and 1 neutropenic sepsis. Nine patients were still on treatment at the cutoff date, 106 had stopped vemurafenib (65 PD, 26 AEs, 3 deaths, 1 doctor's decision, 11 patient's decisions). Conclusion: Vemurafenib provided reasonable response rate and extended PFS in pretreated NSCLC patients with BRAF V600E mutations but was not effective in those with other BRAF mutations. These results emphasize the need of integrating BRAF V600E in routine biomarkers screening.

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