What is the role of docetaxel in treating recurrent high-volume metastatic prostate cancer with androgen deprivation therapy (ADT) and apalutamide?

From the Guidelines

Docetaxel should be added to ADT and apalutamide for recurrent high-volume metastatic prostate cancer, as it provides additional survival benefits in this setting. The standard docetaxel regimen is 75 mg/m² administered intravenously every 3 weeks for 6 cycles, typically with prednisone 5 mg twice daily 1. This triplet approach (ADT + apalutamide + docetaxel) leverages multiple mechanisms of action: ADT reduces testosterone levels, apalutamide blocks androgen receptors, and docetaxel disrupts cancer cell division through microtubule inhibition.

Key Considerations

• The rationale for adding docetaxel stems from clinical trials showing that early docetaxel intensification improves overall survival in high-volume metastatic disease 1.
• Patients should be monitored for docetaxel-related side effects including neutropenia, peripheral neuropathy, and fatigue.
• Prophylactic G-CSF support may be needed, particularly in older patients or those with comorbidities.
• Treatment sequencing should be individualized based on disease characteristics, prior therapies, and patient performance status.

Disease Definition

• High-volume metastatic disease is typically defined as visceral metastases or ≥4 bone lesions with at least one beyond the vertebral column and pelvis.

Study Evidence

• The CHAARTED study showed that docetaxel improved OS (HR 0.72; 95% CI 0.59-0.89) in patients with high-volume disease 1.
• The STAMPEDE trial confirmed the survival advantage of adding docetaxel to ADT in patients with M1 disease 1.
• The NCCN guidelines recommend triplet therapy for patients with high-volume castration-sensitive metastatic prostate cancer who are fit for chemotherapy 1.

From the FDA Drug Label

1. 3 Prostate Cancer Docetaxel Injection in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer.

The addition of docetaxel to ADT and apalutamide for recurrent high-volume metastatic prostate cancer is not directly addressed in the provided drug label. Key points:

• The label indicates that docetaxel is used in combination with prednisone for metastatic castration-resistant prostate cancer.
• There is no mention of apalutamide or the specific context of recurrent high-volume metastatic prostate cancer in the provided label. 2

From the Research

Importance of Adding Docetaxel to ADT and Apalutamide

• The addition of docetaxel to androgen deprivation therapy (ADT) has been shown to improve survival in patients with metastatic, hormone-sensitive prostate cancer 3.
• A systematic review and meta-analysis of individual participant data from randomized trials found that the overall pooled effects of docetaxel plus ADT compared with ADT alone resulted in clear benefits on overall survival, progression-free survival, and failure-free survival 3.
• The relative effect of docetaxel on progression-free survival appeared to be greater with increasing clinical T stage, higher volume of metastases, and, to a lesser extent, synchronous diagnosis of metastatic disease 3.
• For patients with high-volume, clinical T stage 4 disease, the addition of docetaxel to hormone therapy resulted in the largest absolute improvement at 5 years for progression-free survival and overall survival 3.

Role of Docetaxel in Treating Recurrent High-Volume Metastatic Prostate Cancer

• The combination of ADT, apalutamide, and docetaxel may be considered for patients with recurrent high-volume metastatic prostate cancer, as triplet therapy has been ranked first for overall survival and radiographic progression-free survival in this population 4.
• However, the addition of docetaxel to ADT and apalutamide may increase the risk of adverse events, particularly grade ≥3 AEs 4.
• Apalutamide plus ADT has been shown to significantly improve overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer, with a median follow-up of 44.0 months 5.
• The final analysis of the TITAN study confirmed that apalutamide plus ADT improved overall survival, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with metastatic castration-sensitive prostate cancer 5.

Considerations for Treatment

• The decision to add docetaxel to ADT and apalutamide should be based on individual patient characteristics, including the volume of metastases, clinical T stage, and overall health status 3, 4.
• Patients with high-volume metastatic prostate cancer may benefit from the addition of docetaxel to ADT and apalutamide, while those with low-volume disease may not require docetaxel 3, 4.
• The potential benefits and risks of adding docetaxel to ADT and apalutamide should be carefully considered and discussed with patients before making treatment decisions 3, 4, 5.