Phase III Randomized Trial of Docetaxel plus Apalutamide Intensification in Metastatic Hormone-Sensitive Prostate Cancer with Inadequate PSA Response

The primary objective is to evaluate the efficacy of treatment intensification with docetaxel plus apalutamide and androgen deprivation therapy in metastatic hormone-sensitive prostate cancer patients who do not achieve a deep PSA response after initial standard treatment. Efficacy is assessed by event-free survival, which is clinically relevant as a composite measure of disease control and progression-related outcomes. Secondary objectives are to assess additional efficacy outcomes, including time to castration resistance, radiographic progression-free survival, PSA progression-free survival, overall survival, time to subsequent treatment, symptomatic skeletal event-free survival, deep and/or ultradeep PSA response rate at 6 months, and time to initiation of opioid use of at least 7 days. The safety profile of treatment intensification is also evaluated. Quality of life is assessed using the Brief Pain Inventory–Short Form, Brief Fatigue Inventory, and Functional Assessment of Cancer Therapy–Prostate questionnaires.

The trial enrolled 28 male patients with metastatic hormone-sensitive prostate cancer. Participants were adults aged 18 years or older and had histologically or cytologically confirmed adenocarcinoma of the prostate. The study population consisted of patients who had not progressed on apalutamide, were tolerating apalutamide 240 mg daily without toxicity greater than grade 1, and were eligible to continue treatment with apalutamide and ADT without contraindication to docetaxel. Selection was based on a non-deep PSA response after 24 to 30 weeks of initial therapy with standard-of-care ADT and apalutamide. Relevant clinical criteria included ECOG performance status ≤1 and adequate hematologic, hepatic, and renal laboratory values at screening. Sexually active men were required to use effective contraception measures and refrain from sperm donation during the specified treatment periods.

The study is a Phase III randomized, international, open-label, controlled clinical trial in men with metastatic hormone-sensitive prostate cancer who have not achieved a deep PSA response after initial treatment with apalutamide and androgen deprivation therapy. The trial evaluates treatment intensification with docetaxel plus apalutamide and androgen deprivation therapy, with event-free survival as the primary endpoint. The overall trial period is planned from March 2026 to March 2030. Study participation begins with a screening visit to confirm eligibility, including informed consent, disease status, prior treatment exposure, performance status, and required laboratory values. Eligible participants then enter the treatment phase and undergo protocol-specified follow-up visits to assess efficacy, safety, adverse events, and disease progression. An end-of-study visit is performed at the end of participation to document final outcomes and study status. The expected duration of participant involvement is not specified. Early termination may occur if disease progression, unacceptable toxicity, treatment discontinuation, or death is observed, or if eligibility criteria are no longer met.

Apalutamide was administered as film-coated tablets for oral use. The available presentations were Erleada 60 mg and Erleada 240 mg film-coated tablets. The stated dose was 240 mg, with administration in the study context as part of treatment with apalutamide and ADT. The trial description indicated initial treatment with standard-of-care ADT and apalutamide, followed by treatment intensification in participants who did not achieve a deep PSA response. Compliance monitoring was not further specified in the source data.

Docetaxel was administered as a solution for infusion for intravenous use. The product was Docetaxel AqVida 20 mg/ml concentrate for solution for infusion. The stated dose was 75 mg/m2. In the trial, docetaxel was used with apalutamide and ADT as treatment intensification. The source data did not provide a detailed dosing schedule beyond the route and dose. Compliance monitoring was not further specified in the source data.

Efficacy will be assessed by event-free survival as the primary endpoint in patients with metastatic hormone-sensitive prostate cancer who do not achieve a deep PSA response after initial treatment with SOC ADT and apalutamide. Secondary efficacy assessments will include time to castration resistance, radiographic progression-free survival, PSA progression-free survival, overall survival, time to subsequent treatment, symptomatic skeletal event free survival, deep and/or ultradeep PSA response rate at 6 months, and time to initiate opioid use (≥ 7 days). Change from baseline over time will also be evaluated for each subscale of FACT-P, the BPI-SF interference subscale, and BFI.