In a systematic review and meta-analysis reported in JAMA Oncology, Riaz et al found that first-line triplet therapy in metastatic castration-sensitive prostate cancer did not appear to offer an overall survival advantage vs androgen pathway inhibitor doublet therapy.
As stated by the investigators, “The effectiveness of triplet therapy compared with androgen pathway inhibitor doublets in a heterogeneous patient population with metastatic castration-sensitive prostate cancer is unknown.”
Key Findings
The network meta-analysis included 10 phase III randomized trials assessing first-line treatment options for metastatic castration-sensitive prostate cancer, with a total of 11,043 patients in nine unique treatment groups. Evidence in the entire population indicated that the triplet of darolutamide, docetaxel, and androgen-deprivation therapy (ADT; hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.57–0.81) and the triplet of abiraterone, docetaxel, and ADT (HR = 0.75, 95% CI = 0.59–0.95) were associated with improved overall survival vs the docetaxel plus ADT doublet, but not compared with androgen pathway inhibitor doublets of abiraterone plus ADT, enzalutamide plus ADT, or apalutamide plus ADT.
Data were not available by volume of disease for darolutamide, docetaxel, and ADT. Among patients with high-volume disease, abiraterone, docetaxel, and ADT improved overall survival vs docetaxel plus ADT (HR = 0.72, 95% CI = 0.55–0.95) but not compared with abiraterone plus ADT, enzalutamide plus ADT, or apalutamide plus ADT. Among patients with low-volume disease, abiraterone, docetaxel, and ADT did not improve overall survival vs apalutamide plus ADT (HR = 1.45, 95% CI = 0.73–2.89), abiraterone plus ADT (HR = 1.27, 95% CI = 0.68–2.33), enzalutamide plus ADT (HR = 1.14, 95% CI = 0.56–2.32), or docetaxel plus ADT (HR = 0.83, 95% CI = 0.50–1.38).
The investigators concluded, “The potential benefit observed with triplet therapy must be interpreted with careful accounting for the volume of disease and the choice of doublet comparisons used in the clinical trials. These findings suggest an equipoise to how triplet regimens compare with androgen pathway inhibitor doublet combinations and provide direction for future clinical trials.”
Irbaz Bin Riaz, MD, PhD, of Dana-Farber Cancer Institute, is the corresponding author for the JAMA Oncology article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
