Cabazitaxel followed by androgen deprivation therapy (ADT) significantly improves time to progression in patients with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) : A randomized, open label, phase III, multicenter trial

Background: Patients with newly diagnosed mHSPC have a poor prognosis with a 3-year overall survival (OS) rate of 50%. Recently, combination of docetaxel (75mg/m2 every 6 weeks for 6 cycles) with ADT has become a new standard for such patients, based on results of 2 large phase 3 trials showing a significant OS benefit. In these trials, docetaxel was initiated within 3 months after ADT start. Timing of ADT and chemotherapy (CT) is controversial. In breast cancer, endocrine therapy is always started after CT, the rational being that ADT will turn clones of tumor cells in to a stage of dormancy where CT is less effective. Methods: This phase 3 trial randomized newly diagnosed mHSPC patients to receive cabazitaxel (CABA), 25 mg/m2 every 3 weeks for 10 cycles, followed by ADT (immediately after last CABA cycle) versus ADT alone. Primary end-point was OS. Secondary end-point was progression free survival. The study planned to include 400 patients but was closed prematurely due to low inclusion rate. A total 31 patients with newly diagnosed mHSPC were included and here we present the results. Results: Median follow up was 31 month. Of the CABA treated patients, 66.8% got six cycles or more and 46.7% completed all 10 courses. Median OS was 32,5 months with CABA followed by ADT and 29,5 months with ADT alone (HR 1.43, 95% CI 0.38-5.38). Median progression free survival was significantly longer in CABA treated patients (29 vs 12 months, HR 3.96 (95% CI 1.49-10.49). Main grade ≥ 3 toxicities were neutropenia (66%). Conclusions: In conclusion, results from this prematurely terminated trial suggest that CABA followed by ADT is effective in newly diagnosed mHSPC and shows a manageable toxicity. These results have to be validated in larger randomized trials.
Supplement:5, Meeting Abstract: 811P