Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial

BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E -mutated advanced rare cancers: 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 investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS 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 frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E -mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110 . In the final analysis of all cohorts in the phase 2 ROAR basket trial, dabrafenib plus trametinib exhibited tumor-agnostic clinical activity in patients with rare BRAFV800E -mutated cancers, including anaplastic thyroid carcinoma, biliary tract cancer, low-grade glioma and hairy cell leukemia.