Custirsen Fails in Phase 3 Prostate Cancer Trial
Adding custirsen to docetaxel plus prednisone failed to prolong overall survival compared with docetaxel plus prednisone alone in mCRPC.
Adding custirsen to docetaxel plus prednisone failed to prolong overall survival compared with docetaxel plus prednisone alone among patients with metastatic castration-resistant prostate cancer (mCRPC), according to a study published in The Lancet Oncology.1
The international, open-label, phase 3 SYNERGY trial (ClinicalTrials.gov Identifier: NCT01188187) showed no significant difference in overall survival between patients with received custirsen, docetaxel, and prednisone and those given docetaxel plus prednisone alone (hazard ratio, 0.93; 95% CI, 0.79-1.10; P = .415); median overall survival was 23.4 months (95% CI, 20.9-24.8) and 22.0 months (95% CI, 19.5-24.0), respectively.
The 3-drug combination was reasonably well tolerated, with the most common grade 3 or higher adverse events being neutropenia (33%), febrile neutropenia (11%), and fatigue (12%). Investigators observed 1 or more serious adverse events in 43% of patients treated with custirsen vs 36% of those who received docetaxel and prednisone alone. Five percent of patients in each arm died from adverse events.
The study enrolled 1022 patients with mCRPC who had a prostate-specific antigen (PSA) greater than 5 ng/mL and had received no prior chemotherapy. Participants were randomly assigned 1:1 to receive intravenous docetaxel, oral prednisone, and intravenous custirsen weekly, or docetaxel and prednisone alone.
Custirsen is a second-generation antisense oligonucleotide that reduces the production of clusterin, a cytoprotective chaperone protein associated with treatment resistance and upregulated by apoptotic stressors like chemotherapy.
- Chi KN, Higano CS, Blumenstein B, et al. Custirsen in combination with docetaxel and prednisone for patients with metastatic castration-resistant prostate cancer (SYNERGY trial): a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2017 March 7. doi: 10.1016/S1470-2045(17)30168-7 [Epub ahead of print]