Little Evidence of OS Benefit for Orteronel + Prednisone in mCRPC

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Little Evidence of OS Benefit for Orteronel + Prednisone in mCRPC
Little Evidence of OS Benefit for Orteronel + Prednisone in mCRPC

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).”

RELATED: Male Reproductive Cancers Resource Center

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).


  1. Dreicer R, Jones R, Oudard S, et al. Abstract 7. Presented at: 2014 Genitourinary Cancers Symposium. Jan. 30-Feb. 1, 2014; San Francisco.

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