A randomized phase II study of ADT + abiraterone versus ADT + abiraterone + docetaxel in patients with low-volume metastatic hormone-sensitive prostate cancer.

TPS5121 Background: The PEACE-1 and ARASENS phase III trials showed benefit of “triplet” therapy in patients with metastatic hormone sensitive prostate cancer (mHSPC). Triplet therapy is defined as androgen deprivation therapy (ADT), docetaxel and an androgen receptor signaling inhibitor. Both trials showed improved outcomes in patients with a high volume of disease per CHAARTED criteria (≥ 4 bone lesions with ≥1 beyond the axial skeleton or visceral metastasis). The benefit was less clear in patients with low volumes of disease, this may be due to the use of docetaxel as the control arm in this patient population. In the CHAARTED study the benefit of docetaxel in addition to ADT was most pronounced in patients with high volume mHSPC, and the benefit was less certain in low volume disease. To address this uncertainty, we are conducting this phase II trial evaluating ADT/abiraterone versus ADT/abiraterone plus docetaxel in patients with low volume mHSPC. Methods: This is a multisite, randomized trial of ADT (physician’s choice) and abiraterone (1000mg daily + 5 mg prednisone) versus ADT, abiraterone and docetaxel (75 mg/m 2 q3 weeks for 6 cycles). Patients may have started ADT up to 12 weeks prior to randomization. Key eligibility criteria include a tissue-confirmed diagnosis of prostate cancer (PCa) and evidence of metastatic disease on CT, MRI and/or bone scan that meets CHAARTED criteria for low volume disease. Recurrent PCa and exposure to ADT prior to the diagnosis of metastatic disease are allowed, as is concurrent treatment with radiation therapy. The primary objective is to assess and compare radiographic progression free survival (rPFS) between treatment arms. Power calculations assume the median rPFS of the control arm is 33 months (based on the LATITUDE trial) versus 55 months in the docetaxel arm (based on the PEACE-1 trial). A sample size of 120 patients will provide 80% power with a one-sided α = 0.10 Type I error rate based on the log rank test to detect a hazard ratio = 0.60. Assuming a 36-month accrual duration and an additional 3 years of follow up, a total of 70 events are expected to occur on this study. The study will enroll 150 patients (75 per arm) to obtain 120 evaluable patients (assuming a 20% attrition rate). Secondary endpoints include overall survival, PSA response rate, overall response rate, time to castration resistant PCa and time to initiation of subsequent anti-neoplastic therapy. Exploratory endpoints include quality of life assessments and rates of adverse events. Enrollment in this trial began in Dec 2023. It is open at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and other satellite sites affiliated with Northwestern University. Clinical trial information: NCT06060587 .