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]