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
Copyright © 2019 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Clinical lung cancer - 20(2019), 4 vom: 15. Juli, Seite 278-286.e1 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dudnik, Elizabeth [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.04.2020 Date Revised 03.04.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cllc.2019.03.007 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM296803235 |
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| 100 | 1 | |a Dudnik, Elizabeth |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Efficacy and Safety of BRAF Inhibitors With or Without MEK Inhibitors in BRAF-Mutant Advanced Non-Small-Cell Lung Cancer |b Findings From a Real-Life Cohort |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 03.04.2020 | ||
| 500 | |a Date Revised 03.04.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Evaluation Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Dabrafenib | |
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| 700 | 1 | |a Bar, Jair |e verfasserin |4 aut | |
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| 700 | 1 | |a Bshara, Elias |e verfasserin |4 aut | |
| 700 | 1 | |a Kuznetsov, Teodor |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Aharon Yonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Shochat, Tzippy |e verfasserin |4 aut | |
| 700 | 1 | |a Nechushtan, Hovav |e verfasserin |4 aut | |
| 700 | 1 | |a Onn, Amir |e verfasserin |4 aut | |
| 700 | 1 | |a Agbarya, Abed |e verfasserin |4 aut | |
| 700 | 1 | |a Moskovitz, Mor |e verfasserin |4 aut | |
| 700 | 1 | |a Keren, Shoshana |e verfasserin |4 aut | |
| 700 | 1 | |a Popovits-Hadar, Noa |e verfasserin |4 aut | |
| 700 | 1 | |a Urban, Damien |e verfasserin |4 aut | |
| 700 | 1 | |a Mishaeli, Moshe |e verfasserin |4 aut | |
| 700 | 1 | |a Rabinovich, Natalie Maimon |e verfasserin |4 aut | |
| 700 | 1 | |a Brenner, Ronen |e verfasserin |4 aut | |
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| 700 | 1 | |a Roisman, Laila C |e verfasserin |4 aut | |
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| 700 | 0 | |a Israel Lung Cancer Group |e verfasserin |4 aut | |
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