Do Older Patients With Metastatic Hormone-Sensitive Prostate Cancer Benefit From Triplet or Doublet Therapy? A Network Meta-Analysis

Abstract

Introduction: With the expanded approval of androgen receptor axis-targeted (ARAT) agents, clinicians now have more treatment options to offer patients with metastatic hormone-sensitive prostate cancer (mHSPC). Uncertainty remains as to whether older population could benefit similarly from these intensification treatment options.

Patients and methods: A systematic database search was performed for randomized controlled trials (RCTs) evaluating the efficacy of androgen deprivation therapy (ADT) in combination with ARAT agents and/or docetaxel in older patients (aged ≥ 70 or 75 years) with mHSPC. The primary endpoint was overall survival (OS). Indirect comparisons of available treatment options were estimated using a random-effects network meta-analysis.

Results: A total of 11 RCTs were eligible. In comparison with ADT alone or ADT + docetaxel doublet, darolutamide + ADT + docetaxel showed a significant OS benefit, with hazard ratios (HRs) of 0.47 (95% confidence interval [CI]: 0.28-0.77) and 0.61 (95% CI, 0.40-0.93), respectively. However, another triplet (abiraterone + ADT + docetaxel) failed to demonstrate a statistically significant OS benefit, with HRs of 0.61 (95% CI, 0.37-1.02) and 0.80 (95% CI, 0.52-1.24), respectively. Triplet therapies comprising darolutamide and abiraterone ranked first and second, with P score of .90 and .67, respectively, followed by darolutamide + ADT (0.61), apalutamide + ADT (0.60), enzalutamide + ADT (0.56), ADT + docetaxel (0.40), abiraterone + ADT (0.20) and ADT alone (0.06). Furthermore, our data suggest an additional benefit from adding docetaxel as a component of doublet and triplet therapies for older men with mHSPC.

Conclusion: In older patients with mHSPC, triplet therapy comprising darolutamide, ADT, and docetaxel demonstrated the most pronounced OS benefit and ranked highest among currently available treatment options. Further studies are needed to explore the specific toxicities associated with the triplet regimen in this population to better balance oncologic benefits with treatment-related toxicities when making treatment decision.

Keywords: Androgen deprivation therapy; Androgen receptor axis-targeting agent; Treatment intensification.