Phase 3, randomized, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients (pts) with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) (ELM-PC 4 trial)

Genitourinary (Prostate) Cancer
Session Type and Session Title: 
Oral Abstract Session, Genitourinary (Prostate) Cancer
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 5008)
Ronald De Wit, Karim Fizazi, Viorel Jinga, Eleni Efstathiou, Peter C.C. Fong, Manfred Wirth, Kazuhiro Suzuki, Susan Moran, Ling Wang, Hideyuki Akaza, Joel Nelson, Howard I. Scher, Robert Dreicer, Niels Geert Borgstein, Fred Saad; Erasmus University Medical Center, Rotterdam, Netherlands; Institut Gustave Roussy, University of Paris Sud, Villejuif, France; UMF Bucharest, Bucharest, Romania; Alexandra General Hospital of Athens, Oncology Department, Department of Clinical Therapeutics, Medical School, University of Athens, Athens, Greece; Auckland City Hospital, Auckland, New Zealand; University Hospital Carl Gustav Carus Dresden, Dresden, Germany; Gunma University Graduate School of Medicine, Gunma, Japan; Takeda Pharmaceuticals International Co., Cambridge, MA; The University of Tokyo Research Center for Advanced Science and Technology, Tokyo, Japan; University of Pittsburgh, School of Medicine, Pittsburgh, PA; Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY; Cleveland Clinic, Cleveland, OH; University of Montréal Hospital Center, Montréal, QC, Canada

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Abstract Disclosures


Background: Orteronel, an investigational, non-steroidal, selective 17,20-lyase inhibitor, demonstrated improved radiographic PFS (rPFS) but not OS in men with mCRPC post-docetaxel (Dreicer et al, ASCO GU 2014, Abstract 7). The double-blind ELM-PC 4 trial (NCT01193244) evaluated orteronel in pts with chemotherapy-naïve mCRPC. Methods: Men with progressive mCRPC (rising PSA and/or radiographic evidence) and testosterone < 50 ng/dL (post-orchiectomy or with maintained GnRH suppression) were randomized 1:1 to orteronel 400 mg twice daily (BID) + prednisone 5 mg BID (O+P) or placebo + prednisone (P), stratified by region and radiographic progressive disease at baseline. Co-primary endpoints were OS and rPFS. Based on 90% power to test OS (> 90% for rPFS), an initial HR of 1.25 in favor of orteronel was anticipated with 1454 pts and 900 deaths (pre-assigned alpha: OS 0.045, rPFS 0.005). The final analysis for rPFS was conducted at an interim analysis (IA) for OS; the final analysis for OS was conducted at 600 deaths, with 78% power. Results: 1560 pts were randomized. The study met the co-primary endpoint of rPFS; at the IA (final for rPFS), median rPFS with O+P v P was 11 v 8.3 months (HR 0.7; 95% CI: 0.5–0.8; P < .001). At the final analysis for OS the updated median rPFS benefit with O+P v P had increased to 5.1 months (median 13.8 v 8.7 mo; HR 0.7; 95% CI: 0.6–0.8; P < .00001). The co-primary endpoint of OS was not met. Median OS with O+P v P was 31.4 v 29.5 months (HR 0.9; 95% CI: 0.8–1.1; P = .314), with no notable differences across regions. More pts had a ≥ 50% PSA decrease (43% v 25%, P < .00001) and a favorable circulating tumor cell count (15% v 9%, P = .00016) at 12 weeks with O+P v P. Common all-grade adverse events with O+P v P included nausea (36% v 15%), fatigue (34% v 20%), constipation (33% v 15%), and diarrhea (28% v 14%); 30% v 18% of pts discontinued due to AEs. In O+P v P groups, 45% v 51% of pts received subsequent therapy, including docetaxel/abiraterone/enzalutamide in 31%/14%/6% v33%/20%/6%. Conclusion: O+P demonstrated a significant improvement in rPFS but no statistically significant improvement in OS v P in chemotherapy-naive mCRPC. Clinical trial information: NCT01193244.