Study Protocol to Assess Efficacy of Anti-Androgen Therapy plus SBRT in High-Risk Patients

Chicago—The current standard of care in patients with very high risk prostate cancer is radiotherapy and 18 to 28 months of androgen deprivation therapy (ADT); however, according to Sean Matthew McBride, MD, and colleagues, biochemical failure is frequent. Dr. McBride et al. designed a single arm, phase 2 trial to test the hypothesis that stereotactic, hypofractionated radiotherapy (SBRT) delivered with a total of 6 months of apalutamide, abiraterone, and leuprolide will result in a superior 3-year rate of biochemical control in that patient population compared with 42 to 48 conventionally fractionated radiation therapy and long-term ADT. The researchers defined high risk of prostate cancer as Gleason score 9-10 or two high risk features or more than four Gleason 8 cores.

The trial is designed to determine the efficacy of anti-androgen therapy combined with SBRT in very high-risk prostate cancer. The researchers described study protocol during a poster session at the ASCO 2018 Annual Meeting in a poster titled Apalutamide + Abiraterone + Leuprolide with Stereotactic, Ultra-Hypofractionated Radiation (AASUR) in Very High Risk Prostate Cancer (PCa).

The primary end point is the proportion of patients with biochemical failure, defined as nadir plus 2 at 36 months post ADT completion. Eligible patients will receive 6 months of leuprolide, abiraterone, and apalutamide 3 months prior to SBRT; ADT will continue for 3 months post-SBRT. Patient assessment will occur every 4 weeks (±1 week) (cycle=28 days) throughout the study treatment period as well as at least once during SBRT.

Prior to the initiation of SBRT, patients will be required to undergo a prostate biopsy, and two additional biopsies (one at 24 months and, if applicable, upon metastatic progression) will be performed. Partial exome analyses will be performed on all biopsies; additional correlatives include circulating tumor cell evaluation and cell-free DNA measurements pre- and post-treatment.

Should toxicities exceed historical controls, interim analysis will ensure early termination. The study plans to enroll 58 patients; 32 have been enrolled to date. The trial is open at five sites and managed by the Prostate Cancer Clinical Consortium and is funded by Janssen.

Clinical trial information: NCT02772588

Source: McBride SM, Zelefsky MJ, Spratt DE, et al. Apalutamide + abiraterone + leuprolide with stereotactic, ultra-hypofractionated radiation (AASUR) in very high risk prostate cancer (PCa). Abstract of a poster presented at the American Society of Clinical Oncology 2018 Annual Meeting, June 2, 2018, Chicago, Illinois.