Results from a phase 3, randomized, double-blind, multicenter, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy (ELM-PC 5 trial).

Genitourinary Cancer
Session Type and Session Title: 
General Poster Session A: Prostate Cancer
Oral Abstract Session A: Prostate Cancer (eQ&A)
Abstract Number: 
J Clin Oncol 32, 2014 (suppl 4; abstr 7^)
Robert Dreicer, Robert Jones, Stephane Oudard, Eleni Efstathiou, Fred Saad, Ronald De Wit, Johann Sebastian De Bono, Yuanjun Shi, Bindu Tejura, David B. Agus, Niels Geert Borgstein, Joaquim Bellmunt, Karim Fizazi; Cleveland Clinic, Cleveland, OH; Institute of Cancer Sciences, Glasgow, United Kingdom; HEGP, Oncologie Médicale, Paris, France; University of Athens Medical School, Athens, TX; University of Montreal Hospital Center, Montreal, QC, Canada; Erasmus MC Cancer Institute, Rotterdam, Netherlands; The Institue of Cancer Research, The Royal Marsden NHS Foundation Trust, London, United Kingdom; Takeda Pharmaceuticals International Company, Cambridge, MA; Keck School of Medicine of University of Southern California, Beverly Hills, CA; Dana-Farber Cancer Institute, Boston, MA; Institut Gustave Roussy, University of Paris Sud, Villejuif, France

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Orteronel is an investigational, non-steroidal selective inhibitor of 17,20-lyase; a key enzyme in the production of steroidal hormones. Methods: Eligible men with metastatic castration-resistant prostate cancer (mCRPC) had progressive disease (PD; radiographic or prostate-specific antigen), castrate levels of testosterone, and had received more than or equal to 360 mg/m2docetaxel within the prior 6 months. Prior orteronel, abiraterone, or ketoconazole was not permitted. Patients were randomized 2:1 to continuous 28-day cycles of oral orteronel 400 mg BID + prednisone 5 mg BID, or placebo + prednisone without regard to food. Primary endpoint: overall survival (OS); other key endpoints: radiographical progression-free survival (rPFS), 50% or more PSA decrease at 12 weeks, pain response at 12 weeks and safety (NCT01193257). Results: One thousand ninety nine patients were randomized.The study was terminated for failing to meet its primary endpoint: median overall survival (OS) was 17.0 months (95% CI 15.2, 19.9) in patients receiving orteronel versus 15.2 months (95% CI 13.5, 16.9) in those receiving placebo (HR: 0.886 [95% CI: 0.739, 1.062]; P=0.1898). Substantial regional differences were seen in OS benefit: median OS (orteronel vs. placebo) was 20.9 vs. 16.9 mo (HR: 0.889) in North America (n=112), 18.3 vs. 17.8 mo (HR: 1.048) in Europe (n=590), and 15.3 vs 10.1 mo (HR: 0.709) in the rest of the world (n=397). In the overall population, rPFS was significantly improved in the orteronel arm, with a median of 8.3 months vs. 5.7 months in the placebo arm (HR: 0.76 [95% CI: 0.653, 0.885]; P=0.00038). Drug-related adverse events (AEs; any grade) included (orteronel/placebo) nausea (30/16%), vomiting (23/8%), fatigue (17/11%), and diarrhea (16/9%); grade 3 or higher drug-related AEs included increased lipase (12/less than 1%), increased amylase (8/less than 1%), and fatigue (3/3%). Additional sub-analyses looking at potential factors that affected OS will also be reported. Conclusions: Whileorteronel + 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. Clinical trial information: NCT01193257.