SAN FRANCISCO—Adding the investigational selective inhibitor orteronel (TAK-700) to prednisone improves radiographic progression-free survival (rPFS) but not overall survival (OS) among men with metastatic castration-resistant prostate cancer (mCRPC) that had progressed despite docetaxel-based therapy, according to results of a phase 3, randomized, placebo-controlled trial presented during the 2014 Genitourinary Cancers Symposium.
The authors noted marked regional differences in OS.
“While orteronel + prednisone did not show a statistically significant overall OS improvement versus placebo + prednisone, rPFS findings and striking regional OS differences suggest that orteronel has clinically meaningful activity,” reported lead study author Robert Dreicer, MD, of the Cleveland Clinic in Cleveland, OH, and coauthors.
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Orteronel is an experimental non-steroidal selective inhibitor of the steroid hormone-pathway enzyme 17,20-lyase.
Patients who had taken orteronel, abiraterone, or ketoconazole were not enrolled in the study. A total of 1,099 men were randomly assigned 2:1 to receive prednisone (5 mg twice daily) plus either continuous 28-day cycles of oral orteronel (400 mg twice daily) or placebo. The study identified progressive disease using either radiographic or prostate-specific antigen criteria.
The study was terminated early for failing to meet its primary endpoint of superior OS. Median OS was 17.0 months versus 15.2 months (hazard ratio [HR], 0.886; 95% CI: 0.739-1.062; P = 0.1898, not significant).
But rPFS was significantly better in patients receiving orteronel, with a median 8.3 months versus 5.7 months among patients receiving placebo (HR, 0.76; 95% CI: 0.653-0.885; P = 0.00038), the authors reported.
The authors also noted “substantial regional differences” in OS outcomes: “median OS (orteronel vs. placebo) was 20.9 vs. 16.9 months (HR, 0.889) in North America (n = 112), 18.3 vs. 17.8 months (HR, 1.048) in Europe (n = 590), and 15.3 vs. 10.1 months (HR, 0.709) in the rest of the world (n = 397).”
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Drug-associated toxicities included nausea (30% orteronel vs. 16% placebo), vomiting (23% vs. 8%), fatigue (17% vs. 11%), and diarrhea (16% vs. 9%), the researchers reported. Grade 3 or higher drug-related adverse events included increased lipase (12% vs. <1% among patients in the placebo arm), increased amylase (8% vs. <1%), and fatigue (3% vs. 3%).
The 2014 Genitourinary Cancers Symposium is sponsored by the the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO).
