Treatments for BRAF-Mutated NSCLC Depend on Class of Mutation

Lyudmila A. Bazhenova, MD, a medical oncologist and professor of medicine at UC San Diego Health, discusses targeted therapies for patients with BRAF-mutated non–small cell lung cancer (NSCLC).

According to Bazhenova, BRAF mutations include class I, II, and III types. Class I mutations include the V600E mutation, which has a targeted therapy available using the combination of dabrafenib (Tafinlar) and trametinib (Mekinist).

An open-label non-comparative phase 2 trial (NCT01336634) determined that this combination had efficacy for both pretreated and previously untreated patients with BRAF V600E-mutated NSCLC. The overall response rate (ORR) was 68% for the pretreated patients and 64% for treatment-naive patients, and the median progression-free survival (PFS) was 10.2 months for pretreated patients and 10.8 months for previously untreated patients. This combination is now a frontline option for patients who test positive for BRAF V600E mutations.

This combination has not shown efficacy for class II or III BRAF mutations, Bazhenova says. However, ongoing trials of BRAF dimer inhibitors and RAF dimer breakers could offer new approaches to treating these patients with targeted therapies.

TRANSCRIPTION:

0:08 | I also talked about BRAF patients and separating different BRAF mutations, which are currently separated into 3 classes: class I, class II, class III. Your class I mutation is your typical BRAF with 600E mutations where we have data on the efficacy of dabrafenib and trametinib in both first-line setting and the second-line setting showing ORR of 64%, the median PFS of [10.8] months [as first-line therapy]. So, in my practice, I use dabrafenib/trametinib in newly diagnosed patients.

We also know that if you do not have a class I mutation, so-called non-V600E mutations, dabrafenib and trametinib usually do not have any efficacy, so those patients should not be treated for those with those compounds. There are clinical trials with a new class of drugs, which are called BRAF dimer inhibitors and RAF dimer breakers that could be appropriate for those patients.