BRAF-mutant metastatic NSCLC

Dr Stefan Rauh, a medical oncologist at Centre Hospitalier Emile Mayrisch in Luxembourg, discusses targeted therapy for BRAFV600E-mutant metastatic NSCLC, found in about 1-3% of cases. This mutation, significant in melanoma, is targetable in NSCLC, offering hope for improved survival through personalised medicine. Although the number of patients is small, targeted therapy has become a key approach.

Two main treatment regimens are approved for BRAFV600E-mutant metastatic NSCLC. The first, dabrafenib and trametinib, received approval following an open-label, phase 2 trial in both first- and second-line settings. However, significant toxicity, such as diarrhea, vomiting, and fatigue, led to dose reductions or treatment discontinuation in many patients.

A newer combination, encorafenib and binimetinib, approved after another open-label, phase 2 trial, showed less toxicity, including reduced nausea, diarrhea, and fever. Despite the small patient sample size, this combination may be a valuable alternative based on toxicity profiles.

Current guidelines recommend dabrafenib plus trametinib or encorafenib plus binimetinib as preferred first-line treatment options or as subsequent treatment for BRAFV600E-mutant metastatic NSCLC.

In clinical practice, targeted therapy for BRAF-mutant NSCLC is essential, but managing toxicity is crucial. Oncologists must balance treatment efficacy with side effects, adjusting doses to maintain patient quality of life. As the data remains limited due to the rarity of BRAF-mutant NSCLC, future advances in targeted approaches, are eagerly awaited.