(UroToday.com) The 2026 American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting, held in Chicago, IL, will host the Prostate, Testicular, and Penile Cancer – Posters Session. Dr. Enrique Gonzalez-Billalabeitia will present REINFORCE: A phase III randomized trial of treatment intensification with docetaxel in mHSPC patients without deep PSA response after initial apalutamide therapy.
Although ADT plus androgen receptor pathway inhibitors (ARPIs) has become the standard of care for metastatic hormone-sensitive prostate cancer (mHSPC), a substantial proportion of patients fail to achieve a deep PSA response, a biomarker consistently associated with inferior long-term outcomes across multiple phase III studies. Patients without deep PSA decline represent a particularly high-risk subgroup for whom treatment personalization strategies remain limited.
Docetaxel has previously demonstrated survival benefit in high-volume mHSPC and may be particularly beneficial in biologically aggressive disease identified through suboptimal early PSA response. The REINFORCE trial was designed to evaluate a PSA-guided treatment intensification strategy using docetaxel in patients without a deep PSA response following upfront treatment with apalutamide plus ADT.
REINFORCE is an international, multicenter, open-label, phase III randomized study enrolling men ≥18 years old with histologically confirmed mHSPC, ECOG performance status ≤1, and PSA >5 ng/mL at the time of metastatic diagnosis. Additional eligibility criteria include adequate organ function, ≤12 weeks of prior ADT exposure before apalutamide initiation, ongoing treatment with apalutamide plus ADT for 24–30 weeks, absence of disease progression, and failure to achieve a predefined deep PSA response.
Deep PSA response is defined as:
- PSA ≤0.2 ng/mL, or
- PSA decline ≥90% in combination with PSA ≤4 ng/mL
Approximately 320 patients across 85 sites in 6 countries will be randomized 1:1 to:
- Treatment intensification with docetaxel (75 mg/m² every 3 weeks for 6 cycles) combined with continued apalutamide plus ADT, or
- Continued apalutamide plus ADT alone
Randomization is stratified according to:
- Timing of metastatic disease (synchronous vs metachronous)
- Presence of visceral metastases
- PSA at study entry (≤4 vs >4 ng/mL)
The primary endpoint is event-free survival (EFS), defined as time from randomization to PSA progression, radiographic progression involving soft tissue, visceral, or bone lesions according to PCWG3 criteria, or death from any cause.
Secondary endpoints include:
- Time to castration resistance
- Radiographic progression-free survival
- PSA progression-free survival
- Overall survival
- PSA response rates
- Safety
- Patient-reported outcomes
Preliminary pharmacokinetic data suggest apalutamide may reduce docetaxel exposure by approximately 10%. Accordingly, the trial incorporates a dedicated pharmacokinetic substudy evaluating potential drug-drug interactions and bioequivalence when docetaxel is co-administered with apalutamide.
An independent data monitoring committee will oversee patient safety throughout the study, including an early safety review after enrollment of the first 18 patients, assessment of interim efficacy analyses, and evaluation of pharmacokinetic findings to guide recommendations regarding study continuation.
Presented by: Enrique González-Billalabeitia, MD, PhD, Medical Oncologist, Hospital Universitario 12 de Octubre, Madrid, Spain
Written by: Julian Chavarriaga, MD, Clinical Assistant Professor, Urologic Oncologist, Department of Urology at Penn State Health @chavarriagaj on X during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026