Randomized double-blind phase 2 trial of 3 doses of TAS-108 in patients with advanced or metastatic postmenopausal breast cancer
Buzdar A et al. – TAS–108 at 40mg and 80mg daily demonstrated clinical activity with an encouraging duration of benefit. Because of its superior safety profile, TAS–108 40mg daily is recommended for further development.Methods
- In this randomized, double-blind, multicenter study, TAS-108 was administered daily at a dose of 40mg, 80mg, or 120mg to postmenopausal patients with locally advanced, or inoperable, or metastatic hormone-receptor positive breast cancer.
- The primary efficacy outcome was clinical benefit (CB), defined as the total number of patients who achieved a complete response, a partial response, or stable disease for ≥24weeks.
- The study was a 2-stage design in which 19 patients per dose group were planned in the first stage.
- If at least 3 patients in any dose group achieved a CB, then that dose group was to be allowed to continue enrolling for the second stage, and the group could include up to a total of 60 patients.
- The 40-mg and 80-mg groups met the criterion and enrolled patients into the second stage.
- In the 40-mg group, there were 13 CB events in 60 patients (21.7%); and, in the 80-mg group, there were 12 CB events in 60 patients (20%).
- The 120-mg daily dose was stopped early, because it failed to achieve the criterion.
- For the 40-mg and 80-mg groups, the median time to progression was 15.0weeks and 15.9weeks, respectively.
- Only 1 drug-related serious adverse event (grade 3 hyperglycemia) was reported.