CHICAGO, IL USA (UroToday.com) - The novel, oral, high-affinity inhibitor of the androgen receptor, ODM-201, was shown to possess high anticancer activity and a favorable tolerability profile in long-term results from the international phase I/II ARADES study, with data at 38 weeks that were consistent with earlier-reported 12-week efficacy and safety among progressive mCRPC patients.
In results that were presented at the 2015 ASCO Annual meeting, at a median follow-up of 38 weeks, among CRPC patients receiving one of three dose levels of ODM-201, the median time to PSA progression was 36 weeks in chemotherapy-naïve patients, and 21 weeks for patients pretreated with chemotherapy. The median time to radiographic progression was not reached for chemotherapy-naïve patients at final analysis, and was 32 weeks for chemotherapy pretreated patients.
Thirty-two percent (32%) of patients experienced treatment-related adverse events, most commonly asthenia/fatigue (6 patients; 9%), decreased appetite (4 patients; 6%), arthralgia (2 patients; 3%), back pain (2 patients; 3%), diarrhea (2 patients; 3%), headache (2 patients; 3%), hot flushes (2 patients; 3%), and myalgia (2 patients; 3%). Most adverse events were mild to moderate.
Among ARADES-enrolled patients, 69 had progressive mCRPC; 37 patients were chemotherapy-naïve; and 32 were pretreated with chemotherapy. The median age of enrolled patients was 69 years (53-83 years). A total of 59 (86%) of patients had bone metastases and 12 (17%) had visceral disease.
In recent published comments about new nonsteroidal anti-androgens, including ODM-201, with its promising emerging data, as well as enzalutamide and ARN-209, another novel anti-androgen under study, the question was raised about as-yet undetermined differences, in efficacy or safety.
Specifically, whether there are differences in binding affinity to the androgen receptor that are clinically relevant. And, given its molecular size, it was noted that ODM-201 should not cross the blood-brain barrier to the same extent as enzalutamide and ARN-509, another novel anti-androgen agent. But, noted an expert, the most common side effects in the phase I/II study with ODM-201 were fatigue and asthenia. These and other questions will likely be elaborated in the phase III ARAMIS trial, now enrolling subjects.
- Massard C, Fizazi K, Bono P, et al. Long-term efficacy and safety of androgen receptor inhibitor OD-201 in ARADES phase I/II trial. 2015 ASCO Annual Meeting, Chicago, Il. Abstract 5079.
- Re: Activity and Safety of ODM-201 in Patients With Progressive Metastatic Castration-resistant Prostate Cancer (ARDES): An Open-label Phase I Dose Escalation and Randomized Phase 2 Dose Expansion Trial. Expert’s Comments. Eur Urology. 2015;67:347-351.
- Fizazi K, Shore ND, Teuvo L, et al. ARAMIS trial: Efficacy and safety phase 3 trial of ODM-201 in men with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). ASCO 2015 Annual Meeting, Chicago, Il. Abstract TPS5080.
Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting - Illumination & Innovation: Transforming Data into Learning - May 29 - June 2, 2015 - Chicago, Illinois USA
Written by: Barbara Jones for UroToday