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Review
. 2022 Jul:169:102-114.
doi: 10.1016/j.lungcan.2022.05.014. Epub 2022 May 26.

Targeting BRAF-mutant non-small cell lung cancer: Current status and future directions

Affiliations
Review

Targeting BRAF-mutant non-small cell lung cancer: Current status and future directions

Mariona Riudavets et al. Lung Cancer. 2022 Jul.

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.

Keywords: BRAF mutations; MAPK pathway; Non-V600; Non-small cell lung cancer; RAF inhibitors; V600E.

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