TRIPLE-SWITCH (SWOG/CCTG-PR26): A randomized phase III clinical trial for the addition of docetaxel to androgen receptor pathway inhibitors in patients with metastatic castration sensitive prostate cancer (mCSPC) and suboptimal PSA response (NCT06592924).

Abstract

TPS5149 Background: Management of patients (pts) with mCSPC remains a challenge due to its incurable nature and heterogeneous response to androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPI). Analyses of phase III ADT + ARPI trials have indicated that pts with mCSPC with suboptimal PSA response (≥0.2ng/ml at 6-12 months) have a short time to castration-resistance (CRPC) and poor median overall survival (OS) of 30-36 months. There is equipoise about the use of docetaxel in mCSPC pts on ARPI because of: 1) an absence of randomized data for docetaxel in this setting; 2) toxicity of docetaxel with impact on quality of life; and 3) selection of docetaxel treatment by disease volume rather than disease biology. Methods: PR26 is a joint CCTG-SWOG international, open-label, randomized phase III trial comparing continuing standard ADT + ARPI with the addition of up to 6 cycles of docetaxel to ADT + ARPI in mCSPC pts with suboptimal PSA response(PSA ≥0.2 ng/mL after 6-12 months of ADT and ≥4 months of ARPI). Stratification will be based on PSA levels, ARPI type, presence of liver metastasis, disease recurrence status, and time since ADT initiation. The sample size is 830 pts to detect a targeted 33% improvement in overall survival (hazard ratio 0.75) using a 1-sided 0.025 level test with 85% power. Key eligibility criteria are: ≥18 years, histologically confirmed prostate adenocarcinoma, metastatic disease present and confirmed by conventional imaging (CT and/or bone scan), PSA ≥5.0 ng/mL prior to ADT, receipt of ADT for 6-12 months and ARPI for ≥4 months, PSA ≥0.2 ng/mL within 14 days of enrolment, adequate organ and marrow function, ECOG performance status 0-2, eligible for docetaxel chemotherapy, no evidence of disease or biochemical progression on ADT prior to enrolment. Primary endpoint is OS. Secondary endpoints include PSA response, PSA kinetics, and clinical progression free-survival. Correlative studies will explore the prognostic and predictive value of circulating tumor DNA and the association between molecular signatures and clinical outcomes. Conduct to date: Study activation, January 2025. First patient enrolled, May 2025. Accrual to date: 6. Supported by CIHR grant 39527, NCTN grant #CA180863 and CCS grant #707213.