Purpose: Orteronel (TAK-700) is an investigational, non-steroidal, oral, inhibitor of androgen synthesis with greater specificity for 17,20-lyase than for 17α-hydroxylase.
We investigated orteronel without steroids in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC; M0).
Experimental Design: Patients with nmCRPC and rising prostate-specific antigen (PSA) received orteronel 300 mg twice daily until PSA progression, metastases, or unacceptable toxicity. The primary endpoint was percentage of patients achieving PSA ≤ 0.2 ng/mL (undetectable levels) at 3 months. Secondary endpoints included safety, PSA response, time to metastases, and correlated endpoints.
Results: Thirty-nine patients with a median baseline PSA doubling time of 2.4 months (range 0.9‒9.2) received a median of fourteen 28-day treatment cycles. PSA decreased >30% in 35 patients and 6 (16%) achieved PSA ≤ 0.2 ng/mL at 3 months. Median times to PSA progression and metastasis were 13.8 and 25.4 months, respectively. Kaplan-Meier estimates of freedom from PSA progression were 57% and 42% at 12 and 24 months, and of freedom from metastasis were 94% and 62% at 12 and 24 months, respectively. At 3 months, median testosterone declined by 89% from baseline. Adverse events led to therapy discontinuation in 12 patients, and grade ≥3/4 adverse events occurred in 22 patients. Most frequent all-cause adverse events included fatigue (64%), hypertension (44%), diarrhea (38%), and nausea (33%), which were primarily grade 1/2.
Conclusions: Single-agent orteronel produced marked and durable declines in PSA in patients with nmCRPC. Orteronel has moderate but manageable toxicities and its chronic administration without steroids appears feasible.
Written by:
Hussain M, Corn PG, Michaelson MD, Hammers H, Alumkal JJ, Ryan CJ, Bruce JY, Moran S, Lee SY, Lin HM, George DJ. Are you the author?
Hematology/Oncology, University of Michigan; GU Medical Oncology, Unit 1374, MD Anderson; Urologic Oncology, Massachusetts General Hospital Cancer Center; The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University; OHSU Knight Cancer Institute, Oregon Health & Science University; Division of Hematology /Oncology, University of California - San Francisco; Medicine, University of Wisconsin Carbone Cancer Center; Oncology Clinical Research, Takeda Pharmaceuticals International Co; Bioststistics, Takeda Pharmaceuticals International Co; Health Economics and Outcome Research, Millennium: The Takeda Oncology Company; Medicine, Duke University.
Reference: Clin Cancer Res. 2014 Jun 25. pii: clincanres.0356.2014.
doi: 10.1158/1078-0432.CCR-14-0356
PubMed Abstract
PMID: 24965748
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