From the Guidelines
The first-line treatment for advanced adenocarcinoma of the lung with a BRAF mutation is dabrafenib plus trametinib or encorafenib plus binimetinib, as recommended by the NCCN guidelines. This targeted therapy approach is preferred over traditional chemotherapy or immunotherapy for patients with confirmed BRAF V600E mutations 1. Before initiating treatment, comprehensive molecular testing should be performed to confirm the BRAF mutation status. Treatment is typically continued until disease progression or unacceptable toxicity occurs. Some key points to consider when using these combination therapies include:
- Dabrafenib plus trametinib has been shown to have an overall response rate (ORR) of 64% in patients with BRAF V600E mutation-positive advanced or metastatic NSCLC 1
- The median progression-free survival (PFS) of the dabrafenib plus trametinib group was 10.9 months 1
- Common side effects include fever, fatigue, nausea, skin rash, and joint pain, which require monitoring
- For patients who cannot tolerate or access this combination, immunotherapy with or without chemotherapy may be considered as an alternative approach 1
- Single-agent therapy with dabrafenib or vemurafenib can be considered for those who do not tolerate dabrafenib plus trametinib 1
From the Research
First-Line Treatment for Advanced Adenocarcinoma of the Lung with BRAF Mutation
- The combination of dabrafenib and trametinib is the preferred first-line treatment option for patients with advanced BRAF V600-mutated non-small cell lung cancer (NSCLC) 2.
- This combination therapy has shown an objective response rate of 64%, a median progression-free survival of 10.2 months, and a median overall survival of 24.6 months 2.
- For patients with non-V600E BRAF mutations, such as class III BRAF mutations, targeted therapy with dabrafenib and trametinib may also be effective, as demonstrated in a case report of a patient with a BRAF G466V mutation 3.
- BRAF and MEK-targeted therapy (dabrafenib plus trametinib) has been shown to produce longer progression-free survival compared to chemotherapy with or without bevacizumab as a first-line or second-line therapy 4.
Treatment Outcomes and Resistance Mechanisms
- The efficacy of combination therapy involving EGFR TKI, BRAF inhibitor dabrafenib, and MEK inhibitor trametinib in metastatic NSCLC patients with acquired BRAF V600E and EGFR mutations has been demonstrated in case reports 5.
- However, resistance mechanisms to this combination therapy have also been identified, such as the MAP2K1 K57N mutation, which can confer resistance to furmonertinib, dabrafenib, and trametinib combined therapy 6.
- Molecular profiling at progression and exploration of resistance mechanisms can help optimize subsequent treatment strategies for patients with advanced lung adenocarcinoma and BRAF mutations 5, 6.