KEY TAKEAWAYS
- NCT01336634 was a phase 2 study examining the efficacy of dabrafenib + trametinib (dab-tram) in BRAFV600-mutated advanced NSCLC.
- The study aimed to compare the efficacy of dab-tram to other therapeutic options for patients with BRAF-mutated aNSCLC.
- The researchers used real-world data from a de-identified database (2011-2020) to create cohorts and assess treatment impact.
- Results showed a reduced risk of death and prolonged median overall survival with first-line dab-tram versus PBC.
Rare BRAF mutations in patients with NSCLC lead to few therapeutic options. Results from a phase 2 research led to the approval of dabrafenib plus trametinib (dab-tram) for BRAFV600-mutated advanced NSCLC (aNSCLC) (NCT01336634). This study looked back at the results of clinical trials using dab-tram and compared them to the current gold standard of therapy for patients with BRAF-mutated advanced non-small cell lung cancer.
Data from a de-identified real-world database (2011-2020) was used to create cohorts of patients with BRAF-mutated aNSCLC treated with either first-line platinum-based chemotherapy (PBC), first-line ICIs + PBC, or second-line ICIs. The average treatment impact of the treated was estimated using weighting-by-odds.
In unweighted and weighted analyses, the hazard ratio (HR; 95% confidence interval) for death was 0.65 (0.39-1.1) and 0.51 (0.29-0.92; p = 0.03) for first-line dab-tram versus PBC, respectively, and the median overall survival was 17.3 (12.3-40.2) months versus 14.5 (9.2-19.6) months versus 9.7 (6.4-19.6) months. The unweighted and weighted hazard ratios for death comparing first-line dab-tram to PBC plus ICI were 0.56 (0.29-1.1) and 0.57 (0.28-1.17), and the hazard ratios for death comparing second-line dab-tram to ICI were 0.65 (0.39-1.07) and not given (Cox proportional-hazards assumption violated).
The risk of death was reduced, and the median overall survival was prolonged with first-line dab-tram versus PBC in this indirect comparison of individuals with BRAF-mutated aNSCLC. Analyses comparing dab-tram to first-line PBC with ICI or second-line ICI yielded equivocal results with overlapping confidence ranges due to small sample sizes. The study has several flaws, but the information it does provide will be helpful for this special group of patients.
Source:https://pubmed.ncbi.nlm.nih.gov/35592617/
Clinical trial:https://clinicaltrials.gov/ct2/show/NCT01336634
Johnson, B. E., Baik, C. S., Mazieres, J., Groen, H. J. M., Melosky, B., Wolf, J., Zadeh Vosta Kolaei, F. A., Wu, W. H., Knoll, S., Ktiouet Dawson, M., Johns, A., & Planchard, D. (2022). Clinical Outcomes With Dabrafenib Plus Trametinib in a Clinical Trial Versus Real-World Standard of Care in Patients With BRAF-Mutated Advanced NSCLC. JTO clinical and research reports, 3(5), 100324. https://doi.org/10.1016/j.jtocrr.2022.100324
