Vemurafenib in patients (pts) harboring BRAF V600 mutation: Results of non-small cell lung cancer (NSCLC) cohort from the AcSé trial (2018)

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 pts with BRAF-mutated tumors and supporting molecular screening. We report here the results of the NSCLC cohort. Methods: BRAF mutational status was assessed on INCa molecular genetic centers by direct sequencing or NGS. Pts with BRAF V600E mutation, 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 boundary 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 boundary. Results: From 10/2014 to 10/2017, 101 NSCLC pts harboring BRAF V600E were enrolled. Median age: 68 years (range 41–85), 68% smokers, 50% females, 100% non-squamous histology and 19% with ECOG PS 2. Most frequent grade ≥3 adverse events (AEs) were asthenia (10% of pts), epidermoid carcinoma (7%), dermatitis (6%) and increased GGT (6%). Three toxic deaths were reported: 1 nausea and vomiting leading to dehydration, 1 pneumonia and 1 neutropenic sepsis. Among the enrolled pts, 100 BRAF V600E NSCLC pts evaluable for the best overall response (BOR), 43 PR, 21 SD, 16 PD, 12 deaths before assessment and 8 not evaluable (no tumor assessment) were observed. The mean objective response rate was 44.9% (95% CI: 35.2; 54.8), the efficacy boundary was reached with a predictive probability greater than 90%. Median duration of response was 6.5 months (5.1-7.3). Median progression-free survival (PFS) was 5.2 months (3.8-6.9) and median OS was 9.3 months. Nine pts were still on treatment at the cut-off date, 91 have stopped vemurafenib (55 PD, 23 AEs, 3 deaths, 1 doctor’s decision, 9 patient’s decisions). Conclusions: Vemurafenib provided reasonable response rate and prolonged PFS in BRAF V600E pretreated NSCLC. These results confirm the activity of BRAF inhibitors in these pts and underline the need of integrating BRAF V600E in biomarkers routine screening. Clinical trial identification: NCT02304809. Legal entity responsible for the study: UNICANCER. Funding: ARC Foundation French National Cancer Institute (INCa) Roche. Disclosure: J. Mazières: Ad Board, Research grant: Roche, BMS, Astra Zeneca. F. Barlesi: Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis Oncology, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda. V. Avrillon: Advisory Board: Roche, BMS. G. Ferretti: Speaker conference: Boehringer, Roche, GEMS. J.Y. Blay: Advisory Board: Roche, Lilly, Ignyta, Deciphera, Novartis, Bayer, BMS; Corporate-sponsored Research: Roche, Lilly, Ignyta, Deciphera, Novartis, Bayer, Novartis, GSK, AstraZeneca, MSD; Other Substantive Relationships: Surveillance committee of Innate Pharma. All other authors have declared no conflicts of interest.