Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Dabrafenib given in combination with trametinib has shown “promising activity” against biliary tract cancer with a BRAF V600E mutation, report the phase II ROAR trial investigators.
The majority (91%) of the 43 patients recruited to the open-label basket study had primary tumours of the intrahepatic bile ducts, with one case of gallbladder involvement and one perihilar bile duct primary tumour.
The patients were followed up for a median of 10 months after beginning dabrafenib 150 mg twice daily plus trametinib 2 mg/day, with treatment ongoing in 16% of patients at the time of data cutoff.
The investigator-assessed RECIST overall response rate was 51% with a median duration of response of 9 months. And there was a comparable 47% rate of response by independent reviewer assessment, report Vivek Subbiah, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors in The Lancet Oncology.
Investigator-assessed progression-free survival was a median 9 months and overall survival was a median 14 months, which the researchers describe as comparing “favourably with other treatments for biliary tract cancer.”
The study authors say the combination had a “manageable safety profile”, with the most common grade 3 or 4 adverse event (AE) being gamma-glutamyltransferase elevations (12%) and the most common serious treatment-related AE being pyrexia (19%).
Dose reductions and interruptions were required by 35% and 56% of patients, respectively, with one patient discontinuing treatment after sepsis. There were no treatment-related deaths.
Exploratory biomarker analysis included targeted DNA sequencing for 16 patients and showed a “heterogeneous genetic landscape” that did not identify any mutations linked to response, say the researchers. However, the team emphasizes the small number of patients assessed and the need for validation of this finding.
“Together, these observations support the combination of dabrafenib and trametinib as an option for patients with refractory BRAFV600E-mutated biliary tract cancer, a treatment-resistant population for whom, to our knowledge, no effective treatment is currently available”, Vivek Subbiah and co-authors conclude.
They add: “Routine testing for BRAFV600E mutations should be considered in all patients with biliary tract cancer.”
Subbiah V, Lassen U, Élez E, et al. Dabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial. Lancet Oncol; Advance online publication 17 August 2020. https://doi.org/10.1016/S1470-2045(20)30321-1
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