Takeda Pharmaceuticals International Co.;
PubMed | University of Michigan, University of Wisconsin - Madison, Sidney Kimmel Comprehensive Cancer Center, Millennium: The Takeda Oncology Company and 6 more.
Type: Clinical Trial, Phase II | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2014
Orteronel (TAK-700) is an investigational, nonsteroidal, oral, inhibitor of androgen synthesis with greater specificity for 17,20-lyase than for 17-hydroxylase. We investigated orteronel without steroids in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC; M0).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.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.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.