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. 2019 Jul;20(4):278-286.e1.
doi: 10.1016/j.cllc.2019.03.007. Epub 2019 Apr 5.

Efficacy and Safety of BRAF Inhibitors With or Without MEK Inhibitors in BRAF-Mutant Advanced Non-Small-Cell Lung Cancer: Findings From a Real-Life Cohort

Elizabeth Dudnik  1 , Jair Bar  2 , Nir Peled  3 , Elias Bshara  4 , Teodor Kuznetsov  5 , Aharon Yonathan Cohen  6 , Tzippy Shochat  7 , Hovav Nechushtan  8 , Amir Onn  2 , Abed Agbarya  9 , Mor Moskovitz  10 , Shoshana Keren  11 , Noa Popovits-Hadar  12 , Damien Urban  5 , Moshe Mishaeli  13 , Natalie Maimon Rabinovich  13 , Ronen Brenner  14 , Alona Zer  15 , Ofer Rotem  15 , Laila C Roisman  6 , Mira Wollner  16 ; Israel Lung Cancer Group
Affiliations

Efficacy and Safety of BRAF Inhibitors With or Without MEK Inhibitors in BRAF-Mutant Advanced Non-Small-Cell Lung Cancer: Findings From a Real-Life Cohort

Elizabeth Dudnik et al. Clin Lung Cancer. 2019 Jul.

Abstract

Background: Real-life comparative data on BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitors (MEKi) combination in BRAF-mutant (BRAFm) non-small-cell lung cancer (NSCLC) is lacking.

Patients and methods: Consecutive BRAFm advanced NSCLC patients (n = 58) treated in 9 Israeli centers in 2009-2018 were identified. These were divided according to mutation subtype and treatment into groups A1 (V600E, BRAFi; n = 5), A2 (V600E, BRAFi + MEKi; n = 15), A3 (V600E, no BRAFi; n = 7), B1 (non-V600E, BRAFi ± MEKi; n = 7), and B2 (non-V600E, no BRAFi; n = 23); one patient received both BRAFi and BRAFi + MEKi. Safety, objective response rate, progression-free survival with BRAFi ± MEKi, and overall survival were assessed.

Results: Objective response rate was 40%, 67%, and 33% in groups A1, A2, and B1, respectively (P = .5 for comparison between groups A1 and A2). In group B1, G469A and L597R mutations were associated with response to BRAFi + MEKi. Median progression-free survival was 1.2 months (95% confidence interval [CI], 0.5-5.3), 5.5 months (95% CI, 0.7-9.3), and 3.6 months (95% CI, 1.5-6.7) for groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .04). Median overall survival with BRAFi ± MEKi was 1.7 months (95% CI, 0.5-NR), 9.5 months (95% CI, 0.2-14.9), and 7.1 months (95% CI, 1.8-NR) in groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .6). Safety profiles differed slightly, and similar treatment discontinuation rates were observed with BRAFi and BRAFi + MEKi.

Conclusion: In the real-life setting, activity and safety of BRAFi + MEKi in V600E BRAFm NSCLC are comparable to those observed in prospective clinical trials; the combination of BRAFi + MEKi is superior to monotherapy with a BRAFi. Further research should be done to explore the impact of BRAFi + MEKi treatment on the natural history of BRAFm NSCLC.

Keywords: Dabrafenib; Lung cancer; Non-V600E; Trametinib; Vemurafenib.

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