Orteronel to Treat Nonmetastatic Castration-Resistant Prostate Cancer

Chicago—An analysis of an ongoing phase 2 study found that patients with nonmetastatic, castration-resistant prostate cancer (nmCRPC) and rising prostate-specific antigen (PSA) reacted well to and managed toxicities when taking orteronel, an oral investigational drug, as part of a steroid-free regimen.

Results were presented at the ASCO meeting during a poster session. The poster was titled Safety and Activity of the Investigational Agent TAK-700 (Orteronel) Without Prednisone in Men with Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC) and Rising Prostate-Specific Antigen (PSA): Updated Results of a Phase 2 Study.

Patients were included in the study if they were ≥18 years of age, had surgical or ongoing medical castration, and had a histologically or cytologically confirmed diagnosis of adenocarcinoma with no radiographic evidence of metastasis. They also were required to have nmCRPC with progression defined as baseline PSA ≥2 ng/mL and a doubling time ≤8 months or PSA ≥8 ng/mL and a doubling time >8 months.

Exclusion criteria included prior therapy with aminoglutethimide or ketoconazole, antiandrogen therapy within 4 weeks (for flutamide) or within 6 weeks (for all other medications), prior chemotherapy for prostate cancer (other than in the adjuvant setting), and radiation therapy for prostate cancer within 30 days of enrollment.

As of April 13, 2012, the trial included 39 patients who received 300 mg of orteronel twice daily in 28-day treatment cycles without steroids. They took orteronel until PSA progression, metastases, or unacceptable toxicities. The median age was 71 years, 90% of patients were white, and 85% had an Eastern Cooperative Oncology Group Performance Status of 0.

At the data cut-off, 22 of the patients (56%) had been treated for >6 months; the median number of treatment cycles was 7 in the entire group. At 3 months, 16% of the men had PSA ≤0.2 ng/mL, 32% had a ≥90% reduction in PSA, 76% had a ≥50% reduction in PSA, and 82% had a ≥30% reduction in PSA.

After 6 months of treatment, 8% of the men had PSA ≤0.2 ng/mL, 24% had a ≥90% reduction in PSA, 50% had a ≥50% reduction in PSA, and 58% had a ≥30% reduction in PSA.

The authors noted that the Kaplan-Meier estimates of freedom from PSA progression were 97% at 3 months, 91% at 6 months, and 60% at 12 months. The median time to PSA progression was 14.8 months. In addition, the Kaplan-Meier estimates of freedom from mestasis were 97% at 6 and 12 months.

The most common adverse events (AEs) were fatigue (occurring in 62% of patients), diarrhea (38%), hypertension (38%), nausea (36%), and decreased appetite (31%). Two patients discontinued the study because of adrenal insufficiency. Ten men had serious AEs, and 3 men had grade 4 AEs.

This study was supported by Millennium Pharmaceuticals, Inc.