In combination with docetaxel, apatorsen significantly improves overall survival compared with docetaxel alone among patients with metastatic bladder cancer who had progressed following first-line platinum-based chemotherapy, according to preliminary findings of the phase 2 Borealis-2 trial.1
Apatorsen is a once-weekly intravenous investigational heat shock protein 27 inhibitor designed to overcome treatment resistance. Because early trials have suggested that apatorsen possesses both single-agent activity and synergistic activity in combination with other agents, researchers evaluated the efficacy and tolerability of second-line apatorsen plus docetaxel among patients with metastatic bladder cancer.
For the open-label study (ClinicalTrials.gov Identifier: NCT01780545), researchers enrolled 200 patients with locally advanced or metastatic urothelial carcinoma who were relapsed or refractory to platinum-based chemotherapy.
Participants were randomly assigned to receive apatorsen on days 1, 8, and 15 of each 21-day cycle after a loading dose period plus docetaxel on day 1 of each cycle, or docetaxel alone. In both arms, patients received docetaxel for a maximum of 10 cycles. Apatorsen was continued as maintenance therapy in the intervention arm in patients who did not experience disease progression.
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Patients who received apatorsen had a 20% reduction in the risk of death compared with those who received docetaxel alone (hazard ratio, 0.80; 95% CI, 0.65-0.98; P = .078). The primary analysis was a superiority test of overall survival, performed at a 1-sided 0.10 significance level; the study therefore met its primary endpoint of overall survival.
The safety profile of apatorsen plus docetaxel was similar to that of docetaxel monotherapy. No new safety signals with apatorsen were observed.
- OncoGenex announces positive survival results from apatorsen phase 2 Borealis-2 trial in metastatic bladder cancer. OncoGenex website. http://ir.oncogenex.com/releasedetail.cfm?ReleaseID=995427. Updated October 25, 2016. Accessed October 26, 2016.