Elizabeth Dudnik1, Jair Bar2, Nir Peled3, Elias Bshara4, Teodor Kuznetsov5, Aharon Yonathan Cohen6, Tzippy Shochat7, Hovav Nechushtan8, Amir Onn2, Abed Agbarya9, Mor Moskovitz10, Shoshana Keren11, Noa Popovits-Hadar12, Damien Urban5, Moshe Mishaeli13, Natalie Maimon Rabinovich13, Ronen Brenner14, Alona Zer15, Ofer Rotem15, Laila C Roisman6, Mira Wollner16. 1. Thoracic Cancer Service, Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel. Electronic address: elizabetadu@clalit.org.il. 2. Thoracic Oncology Service, Institute of Oncology, Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Soroka University Medical Center, The Cancer Institute, Beer-Sheva, Israel; Ben Gurion University of the Negev, Beer-Sheva, Israel. 4. Thoracic Cancer Service, Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. Thoracic Oncology Service, Institute of Oncology, Sheba Medical Center, Ramat Gan, Israel. 6. Soroka University Medical Center, The Cancer Institute, Beer-Sheva, Israel. 7. Statistical Consulting Unit, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel. 8. Oncology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel. 9. Oncology Department, Bney Zion Medical Center, Haifa, Israel. 10. Thoracic Cancer Service, Rambam Health Care Campus, Haifa, Israel. 11. Oncology Department, Lin Medical Center (associated with Carmel Hospital), Haifa, Israel. 12. Thoracic Cancer Service, Rambam Health Care Campus, Haifa, Israel; Oncology Department, Lin Medical Center (associated with Carmel Hospital), Haifa, Israel. 13. Oncology Department, Meir Medical Center, Kfar Sava, Israel. 14. Oncology Department, Wolfson Medical Center, Holon, Israel. 15. Thoracic Cancer Service, Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel. 16. Thoracic Cancer Service, Rambam Health Care Campus, Haifa, Israel; The Technion, Israeli Institute of Technology, Technion City, Haifa, Israel.
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.
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 NSCLCpatients (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.
Authors: Alessandro Russo; Ana Rita Lopes; Michael G McCusker; Sandra Gimenez Garrigues; Giuseppina R Ricciardi; Katherine E Arensmeyer; Katherine A Scilla; Ranee Mehra; Christian Rolfo Journal: Curr Oncol Rep Date: 2020-04-16 Impact factor: 5.075