BRAF Inhibitors in Non-Small Cell Lung Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. MAPK Pathway and Its Alterations
2.1. BRAF and MEK Alterations in NSCLC
2.2. BRAF and MEK Inhibitors in NSCLC
3. Discussion
Trial | Phase | Setting | Stage | Pts | Treatment | Primary Endpoints |
---|---|---|---|---|---|---|
NCT04526782 (ENCO-BRAF Trial) [59] | Phase 2 | Naïve or subsequent lines (two different arms) | Extensive stage | 119 | Encorafenib + Binimetinib | ORR |
NCT03915951 [60] | Phase 2 | Any line of treatment | Extensive stage | 97 | Encorafenib + binimetinib | ORR |
NCT04585815 (Landscape 1011 trial) [62] | Phase 1/2 | Any line of treatment | Extensive stage | 375 | Sasalnimab + encorafenib + binimetinib | Durable objective response rate |
NCT04591431 (ROME trial) [63] | Phase 2 | Subsequent lines (no more than two treatments are allowed) | Extensive stage | 384 | Vemurafenib + cobimetinib vs. SOC * | ORR |
NCT03178552 (BFAST Trial) [64] | Phase 2/3 | First line | Extensive stage | 1000 | Vemurafenib + Cobimetinib+ Atezolizumab | Time in response (TIR) |
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Study | Author | Setting | Pts | Treatment | Response Rate (%) | Disease Control Rate (%) | Progression-Free Survival (Months) | Overall Survival (Months) | Toxicity |
---|---|---|---|---|---|---|---|---|---|
Phase 2 (VE-BASKET study) | Subbiah, 2019 [41] | Advanced solid tumours, Cohort NSCLC BRAFV600 | 62 | Vemurafenib | 37.1 | - | 6.5 | 15.4 | Nausea, hyperkeratosis, decreased appetite, arthralgia, cutaneous SCC |
Phase 2 (AcSé-BASKET study) | Mazieres, 2020 [42] | Advanced solid tumours, Cohort NSCLC: BRAFnonV600 BRAFV600 | 115 15 100 | Vemurafenib | 0 44.8 | - - | 1.8 5.2 | 5.2 10 | Asthenia, decreased appetite, acneiform dermatitis, nausea and diarrhoea |
Phase 2 (BRF113928) | Planchard 2016; 2022 [43,44,45] | BRAFV600E advanced NSCLC: Cohort A pretreated Cohort B pretreated Cohort C naïve | 171 78 57 36 | Dabrafenib Dabrafenib+ Trametinib Dabrafenib+ Trametinib | 33 68.4 63.9 | 58 80.7 75 | 5.5 10.2 10.8 | 12.7 18.2 17.3 | Pyrexia, asthenia, hyperkeratosis, decreased appetite, nausea |
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Sforza, V.; Palumbo, G.; Cascetta, P.; Carillio, G.; Manzo, A.; Montanino, A.; Sandomenico, C.; Costanzo, R.; Esposito, G.; Laudato, F.; et al. BRAF Inhibitors in Non-Small Cell Lung Cancer. Cancers 2022, 14, 4863. https://doi.org/10.3390/cancers14194863
Sforza V, Palumbo G, Cascetta P, Carillio G, Manzo A, Montanino A, Sandomenico C, Costanzo R, Esposito G, Laudato F, et al. BRAF Inhibitors in Non-Small Cell Lung Cancer. Cancers. 2022; 14(19):4863. https://doi.org/10.3390/cancers14194863
Chicago/Turabian StyleSforza, Vincenzo, Giuliano Palumbo, Priscilla Cascetta, Guido Carillio, Anna Manzo, Agnese Montanino, Claudia Sandomenico, Raffaele Costanzo, Giovanna Esposito, Francesca Laudato, and et al. 2022. "BRAF Inhibitors in Non-Small Cell Lung Cancer" Cancers 14, no. 19: 4863. https://doi.org/10.3390/cancers14194863