KEY TAKEAWAYS
- This Phase 2 ROAR trial of dabrafenib and trametinib combination therapy was conducted on patients with BRAFV600E-mutated cancers.
- The primary endpoint was an investigator-assessed overall response rate in eight patient cohorts.
- Secondary endpoints included median duration of response, progression-free survival, overall survival, and safety data.
- Results showed encouraging tumor-agnostic treatment activity, with median overall survival ranging from 13.5 to 33.9 months.
The phase 2 basket trial evaluated the combination of dabrafenib (a BRAF kinase inhibitor) and trametinib (a MEK inhibitor) in eight cohorts of patients who had advanced rare cancers with BRAFV600E mutations is studied. These cohorts included patients with anaplastic thyroid carcinoma (n=36), biliary tract cancer (n=43), gastrointestinal stromal tumor (n=1), adenocarcinoma of the small intestine (n=3), low-grade glioma (n=13), high-grade glioma (n=45), hairy cell leukemia (n=55), and multiple myeloma (n=19). The primary endpoint of ORR was evaluated, and the results were: 56%, 53%, 0%, 67%, 54%, 33%, 89%, and 50%, respectively. The secondary endpoints included median DoR, PFS, OS, and safety. For each cohort, the median DoR was 14.4 months, 8.9 months, 7.7 months, 31.2 months, not reached, and 11.1 months, respectively. Following each cohort, the median PFS was 6.7 months, 9.0 months, not attained, not evaluable, 9.5 months, 5.5 months, not evaluable, and 6.3 months. The median OS for each cohort was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable, and 33.9 months, respectively. The most common treatment-related adverse events (occurring in at least 20% of patients) were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%), and rash (20.4%). These results indicate that the combination of dabrafenib and trametinib may have a promising therapeutic potential as a tumor-agnostic treatment option for patients.
Source: https://pubmed.ncbi.nlm.nih.gov/37059834/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02034110
Subbiah V, Kreitman RJ, Wainberg ZA, Gazzah A, Lassen U, Stein A, Wen PY, Dietrich S, de Jonge MJA, Blay JY, Italiano A, Yonemori K, Cho DC, de Vos FYFL, Moreau P, Fernandez EE, Schellens JHM, Zielinski CC, Redhu S, Boran A, Passos VQ, Ilankumaran P, Bang YJ. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. Nat Med. 2023 Apr 14. doi 10.1038/s41591-023-02321-8. Epub ahead of print. PMID: 37059834.
