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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)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.
Abstracts by Ronald De Wit:
A randomized phase II multicenter trial on the effects of budesonide on cabazitaxel-induced diarrhea: CABARESC.Meeting: 2016 ASCO Annual Meeting | Abstract No: 5073
KEYNOTE-057: Phase 2 study of pembrolizumab for patients (pts) with Bacillus Calmette Guerin (BCG)-unresponsive, high-risk non-muscle-invasive bladder cancer (NMIBC).Meeting: 2016 ASCO Annual Meeting | Abstract No: TPS4576
Final analysis of COMET-1: Cabozantinib (Cabo) versus prednisone (Pred) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) previously treated with docetaxel (D) and abiraterone (A) and/or enzalutamide (E).Meeting: 2015 Genitourinary Cancers Symposium | Abstract No: 139