From the Guidelines
Triplet therapy is the most effective treatment approach for high-volume castration-resistant metastatic prostate cancer, as it has been shown to improve overall survival and progression-free survival compared to standard approaches. The most common triplet regimen combines androgen receptor pathway inhibitors (such as abiraterone acetate or enzalutamide) with docetaxel chemotherapy and androgen deprivation therapy (ADT) 1. For example, the PEACE-1 trial showed that adding abiraterone (1000mg daily) plus prednisone (5mg daily) to ADT and docetaxel improved median overall survival by approximately 1.5 years in high-volume metastatic disease. Similarly, the ARASENS trial demonstrated that darolutamide (600mg twice daily) combined with ADT and docetaxel reduced the risk of death by 32.5% compared to ADT plus docetaxel alone 1.
Some key points to consider when using triplet therapy include:
- The efficacy of triplet therapy is believed to result from simultaneous targeting of multiple cancer growth pathways, providing more comprehensive blockade of androgen signaling while directly attacking cancer cells through cytotoxic mechanisms, which is particularly important in high-volume disease where rapid disease control is crucial.
- Patients require regular monitoring for side effects including fatigue, hypertension, liver function abnormalities, and myelosuppression.
- The survival benefit of triplet therapy is more pronounced in patients with high-volume disease, with a hazard ratio of 0.63 (95% CI, 0.50–0.79; P,.001) in subgroup analysis 1.
- Triplet therapy is typically initiated at diagnosis and continued until disease progression or unacceptable toxicity.
Overall, the use of triplet therapy is recommended for patients with high-volume castration-resistant metastatic prostate cancer who are fit for chemotherapy, as it has been shown to improve overall survival and progression-free survival compared to standard approaches 1.
From the Research
Efficacy of Triplet Therapy in High-Volume Castration-Resistant Metastatic Prostate Cancer
- The provided studies primarily focus on metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-sensitive prostate cancer (mCSPC), with limited direct information on high-volume castration-resistant metastatic prostate cancer (CRPC) [ 2, 3, 4, 5, 6 ].
- However, the evidence suggests that triplet therapy, consisting of androgen-deprivation therapy (ADT), an androgen receptor pathway inhibitor (ARPI), and docetaxel, improves overall survival in patients with mCSPC, particularly those with high-volume disease [ 2, 4, 5 ].
- The studies demonstrate that triplet therapy is effective in improving overall survival and progression-free survival in patients with mCSPC, with hazard ratios ranging from 0.68 to 0.82 [ 2, 4, 5 ].
- Real-world evidence from an Austrian multicenter study confirms the effectiveness and tolerability of triplet therapy in patients with mHSPC, with a significant proportion of patients achieving a PSA decline and imaging response [ 6 ].
Key Findings
- Triplet therapy improves overall survival in patients with mCSPC, particularly those with high-volume disease [ 2, 4, 5 ].
- The combination of ADT, ARPI, and docetaxel is effective in improving overall survival and progression-free survival in patients with mCSPC [ 2, 4, 5 ].
- Real-world evidence confirms the effectiveness and tolerability of triplet therapy in patients with mHSPC [ 6 ].