From the Guidelines
Adding docetaxel to ADT plus apalutamide is a recommended treatment option for high volume metastatic prostate cancer recurring after definitive initial treatment, as it has shown to improve outcomes in terms of morbidity, mortality, and quality of life. The standard approach for high-volume disease typically begins with ADT using LHRH agonists or antagonists, often combined with more potent agents such as docetaxel chemotherapy or novel hormonal therapies like apalutamide 1. According to the ASCO guideline update, the combination of ADT and docetaxel is a standard of care for men with high-volume de novo M1 disease 1.
For patients with high volume metastatic prostate cancer recurring after definitive initial treatment, the treatment options include:
- ADT using LHRH agonists (leuprolide 7.5mg monthly or 22.5mg every 3 months) or antagonists (degarelix 240mg loading dose followed by 80mg monthly)
- Intensification of ADT with either docetaxel chemotherapy (75mg/m² every 3 weeks for 6 cycles with prednisone 5mg twice daily) or novel hormonal therapies like apalutamide (240mg daily)
- Additional options for patients with progressive disease despite ADT, including cabazitaxel chemotherapy (20-25mg/m² every 3 weeks), radium-223 (for bone-predominant disease, 55 kBq/kg IV every 4 weeks for 6 cycles), or PARP inhibitors like olaparib (300mg twice daily) for those with homologous recombination repair gene mutations
- Palliative radiation therapy may be used for symptomatic bone metastases 1.
Treatment selection should be individualized based on disease characteristics, prior therapies, comorbidities, and patient preferences, with close monitoring for disease progression and treatment side effects 1. The ASCO Expert Panel recommends that treatment options be guided by the most recent and highest quality evidence, and that patients be closely monitored for disease progression and treatment side effects 1.
From the FDA Drug Label
The safety and efficacy of Docetaxel Injection in combination with prednisone in patients with metastatic castration-resistant prostate cancer were evaluated in a randomized multicenter active control trial A total of 1006 patients with Karnofsky Performance Status (KPS) ≥60 were randomized to the following treatment groups: Docetaxel Injection 75 mg/m2 every 3 weeks for 10 cycles. Docetaxel Injection 30 mg/m2 administered weekly for the first 5 weeks in a 6-week cycle for 5 cycles. Mitoxantrone 12 mg/m2 every 3 weeks for 10 cycles All 3 regimens were administered in combination with prednisone 5 mg twice daily, continuously.
There is no direct information in the provided drug labels that supports the benefits of adding Docetaxel to ADT plus apalutamide in the case of high volume metastatic prostate cancer recurring 3 years after definitive initial treatment. The labels discuss the use of Docetaxel in combination with prednisone for metastatic castration-resistant prostate cancer, but do not provide information on its use with ADT plus apalutamide. 2 2
Key points:
- Docetaxel is used in combination with prednisone for metastatic castration-resistant prostate cancer.
- There is no direct information on the use of Docetaxel with ADT plus apalutamide.
- The provided drug labels do not support the benefits of adding Docetaxel to ADT plus apalutamide in the specified scenario.
From the Research
Treatment Options for High-Volume Metastatic Prostate Cancer
- The addition of docetaxel to androgen deprivation therapy (ADT) has been shown to improve overall survival (OS) in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) 3.
- Triplet therapy, which includes androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus ADT, has been found to outperform doublet therapy in terms of OS and progression-free survival (PFS) in patients with mHSPC 4, 5.
- The ranking analysis showed that triplet therapy had the highest likelihood of improved OS in patients with high-volume disease, while doublet therapy using ARSI + ADT had the highest likelihood of improved OS in patients with low-volume disease 4, 5.
Benefits of Adding Docetaxel to ADT plus Apalutamide
- There is evidence to suggest that adding docetaxel to ADT plus apalutamide may improve OS and PFS in patients with high-volume mHSPC 6, 7.
- However, the optimal selection of patients who would benefit most from this combination therapy remains unclear 4.
- Further studies are needed to confirm the benefits of adding docetaxel to ADT plus apalutamide in patients with high-volume mHSPC 5.
Comparison of Treatment Regimens
- A network meta-analysis found that triplet therapy (DAR + DOC + ADT and ABI + DOC + ADT) had the greatest improvement in OS, followed by REZ + ADT 6.
- Another study found that triplet therapy outperformed DOC + ADT in terms of OS and PFS, with no statistically significant difference between patients with low- and high-volume disease 5.
- The ranking analysis showed that darolutamide plus docetaxel plus ADT had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT had the highest in patients with low-volume disease 4.