Role of BRAF Mutations in Non-Small Cell Lung Cancer Still Emerging, Evolving

Global results from the study suggested that 9 patients with BRAF^V600E mutations exposed to dabrafenib responded similarly to those treated with vemurafenib. A phase 2 trial of dabrafenib monotherapy in BRAF^V600E NSCLC resulted in a 33% objective response rate and a 58% disease control rate.⁶ Later, an additional cohort testing dabrafenib plus trametinib showed improved responses, with 67% of patients having disease response.⁷

“Moving the combination therapy in the first-line setting, responses and control of the disease were documented at similar rates when compared to the pretreated patients,” Dr Leonetti and colleagues wrote.

Based on these results, the FDA approved this drug combination in patients with NSCLC with BRAF^V600E mutation.

Future Directions

According to the review, future research will need to explore and clarify the role of immunotherapy in patients with BRAF-mutated NSCLC. Checkpoint inhibitors have been shown to be effective in tumors with high mutational burden.

“Considering that BRAF mutations are often found in smokers, in which a higher mutational load has been reported, immunotherapy could represent a strategy in this population,” they wrote.

References

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3. Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicenter, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386:444-451.
4. Hyman DM, Puzanov I, Subbiah V, et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015;373:726-736.
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6. Planchard D, Kim TM, Mazieres J, et al. Dabrafenib in patients with BRAFV600E-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17:642-650.
7. Planchard D, Besse B, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously treated BRAF V600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016;17:984-993.