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. In the Docetaxel Injection every three week arm, a statistically significant overall survival advantage was demonstrated compared to mitoxantrone. Efficacy results for the Docetaxel Injection every 3 week arm versus the control arm are summarized in Table 18 and Figure 5 Table 18: Efficacy of Docetaxel Injection in the Treatment of Patients with Metastatic Castration- Resistant Prostate Cancer (Intent-to-Treat Analysis) Docetaxel Injection + Prednisone every 3 weeks Mitoxantrone + Prednisone every 3 weeks Number of patients Median survival (months) 95% CI Hazard ratio 95% CI p-value* 335 18.9 (17.0-21.2) 0.761 (0.619-0.936) 0.0094 337 16.5 (14.4-18. 6) - - -
The use of triplet therapy is not directly mentioned in the provided drug labels as a treatment for castrate-resistant prostate cancer. However, Docetaxel Injection in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer.
- The efficacy of Docetaxel Injection in combination with prednisone was evaluated in a randomized multicenter active control trial.
- A statistically significant overall survival advantage was demonstrated compared to mitoxantrone in the Docetaxel Injection every three week arm.
- The median survival was 18.9 months for the Docetaxel Injection + Prednisone every 3 weeks arm, compared to 16.5 months for the Mitoxantrone + Prednisone every 3 weeks arm. However, the question of whether triplet therapy is effective against castrate-resistant prostate cancer cannot be directly answered based on the provided information 1.
From the Research
Triplet therapy is effective against castrate-resistant prostate cancer, with the most recent and highest quality study 2 demonstrating improved overall survival and progression-free survival compared to standard dual therapy. The most studied triplet combination includes androgen receptor pathway inhibitors (like enzalutamide or abiraterone) plus a taxane chemotherapy agent (docetaxel) and androgen deprivation therapy (ADT).
- Recent clinical trials, such as the PEACE-1 trial 3, demonstrate that this approach can significantly improve progression-free survival and potentially overall survival compared to standard dual therapy.
- Another emerging triplet approach combines ADT with PARP inhibitors (like olaparib) and AR pathway inhibitors for patients with specific genetic mutations, particularly in DNA repair genes like BRCA1/2.
- The rationale behind triplet therapy is that it targets multiple cancer survival pathways simultaneously, potentially overcoming resistance mechanisms that develop with single or dual agent approaches. However, triplet therapy typically comes with increased toxicity, including fatigue, gastrointestinal effects, and myelosuppression, requiring careful patient selection and monitoring, as seen in studies such as 4 and 5. In terms of specific treatment regimens, the study by 2 found that triplet therapy with darolutamide or abiraterone with docetaxel and ADT improved overall survival, with a hazard ratio of 0.70 (95%CI 0.61-0.80) compared to docetaxel+ADT. Overall, the evidence suggests that triplet therapy is a promising approach for the treatment of castrate-resistant prostate cancer, with potential benefits in terms of overall survival and progression-free survival, although careful consideration of toxicity and patient selection is necessary.