Targeting BRAF-mutant non-small cell lung cancer: Current status and future directions. (July 2022)

• Record Type: Journal Article
• Authors: Riudavets, Mariona; Cascetta, Priscilla; Planchard, David
• Is Part Of: Lung cancer. Volume 169(2022)
• Page Start: 102
• Page End: 114
• Publication Date: 2022-07
• Subjects: BRAF mutations -- V600E -- Non-V600 -- Non-small cell lung cancer -- MAPK pathway -- RAF inhibitors; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2022.05.014
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Vemurafenib and dabrafenib showed relevant clinical activity in pre-treated NSCLC with BRAF V600E mutations Dabrafenib/trametinib demonstrated its superiority in pre-treated and treatment-naïve BRAF V600E-mutant NSCLC Available efficacy data on BRAF V600 non-E mutations suggests a comparable efficacy of BRAF/MEK inhibitors Limited activity of BRAF/MEK inhibitors has been observed in BRAF non-V600E mutations Abstract: Lung cancer harbouring BRAF mutations accounts for 4% of all non-small cell lung cancer (NSCLC) cases, identifying a relevant subset of patients that need to be promptly managed. Three subtypes of BRAF mutations have been described: class I (V600E), and class II and III (non-V600), with different prognostic and predictive outcomes. Pivotal phase II trials have demonstrated the efficacy of the double BRAF/MEK inhibition with dabrafenib plus trametinib in patients harbouring V600E mutations, making BRAF a mandatory requirement in the genetic portrait of advanced non-squamous lung cancer patients. However, non-V600 mutations represent around 50% of BRAF -mutant NSCLC patients, for which no specific targeted approaches are approved. A paradigm shift from the double BRAF/MEK inhibition to combinations with agents with distinct mechanisms of action, such as immune-checkpoint inhibitors, pan-RAF and selective ERK 1/2 inhibitors, is under investigation and may change the therapeutic landscape of BRAF -driven NSCLC. This paper provides a practical, concise and updated review on the therapeutic strategies in NSCLC with BRAF mutations.