(UroToday.com) The 2025 ASCO annual meeting featured a prostate cancer trials in progress session and a presentation by Dr. Michael Ong discussing 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.
Management of patients with mCSPC remains a challenge due to its incurable nature and heterogeneous response to ADT and androgen receptor pathway inhibitors. Recent analyses of phase III ADT + androgen receptor pathway inhibitor trials show that mCSPC with suboptimal PSA response (≥0.2 ng/ml at 6-12 months) have poor prognosis, short time to castration-resistance (CRPC) and a 30-36 month median overall survival.
While docetaxel could also be utilized in mCSPC, there is equipoise about its use in androgen receptor pathway inhibitors-treated patients because of (i) an absence of randomized data for docetaxel in this setting, (ii) toxicity of docetaxel with impact on quality of life for patients, and (iii) selection of docetaxel treatment by disease volume rather than disease biology. CCTG-PR26 (TRIPLE-SWITCH) is a joint CCTG-SWOG trial run through the NCI National Clinical Trials Network. This study investigates whether adding docetaxel prior to development of CRPC, regardless of disease volume, will improve overall survival in androgen receptor pathway inhibitor-treated mCSPC patients that show evidence of suboptimal response.
This international, open-label, randomized phase III trial compares standard ADT + androgen receptor pathway inhibitors against the addition of docetaxel to ADT + androgen receptor pathway inhibitors in mCSPC patients with suboptimal PSA response, defined as PSA ≥0.2 ng/mL after 6-12 months of ADT and ≥4 months of androgen receptor pathway inhibitors. Stratification will be based on PSA levels, androgen receptor pathway inhibitor type, presence of liver metastasis, disease recurrence status, and time since ADT initiation.
Arm 1 will continue standard ADT + androgen receptor pathway inhibitors (abiraterone acetate with prednisone, apalutamide, enzalutamide or darolutamide). Arm 2 will receive docetaxel 75mg/m2 IV every 3 weeks for up to 6 cycles in addition to continuing standard ADT + androgen receptor pathway inhibitors:
The sample size is 830 patients in order 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 androgen receptor pathway inhibitors 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 progression or biochemical progression on ADT prior to enrolment
The primary endpoint is overall survival, and 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 in primary prostate cancer tissue and clinical outcomes.
Enrolment has been initiated in January 2025 and is ongoing.
Presented by: Michael Ong, MD, FRCPC, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.
Related content: TRIPLE-SWITCH Trial: Intensifying Treatment for Suboptimal PSA Response in mHSPC - Michael Ong, Alexandra Sokolova & Tanya Dorff