Emergence of triplet therapy for metastatic castration-sensitive prostate cancer: An updated systematic review and network meta-analysis

Introduction: There have been a growing number of treatment options available for men with metastatic castration-sensitive prostate cancer. Not only have newer agents entered the clinical landscape, there is a trend toward treatment intensification by combining multiple agents simultaneously. We aim to assess the best contemporary treatment option for men with mCSPC.Materials and methods: We perform an updated systematic review and network meta-analysis of randomized control trials that evaluated systemic therapies in men with castration-sensitive prostate cancer. We searched multiple databases up to April 2022. We included all randomized trials assessing the effect of systemic agents. We performed subgroup analyses based on disease volume and timing of presentation. Statistical analysis was performed with Bayesian methods.Results: We found 10 eligible trials with 10,065 patients who were included in this analysis. Triplet therapy with darolutamide or abiraterone with docetaxel and ADT improved overall survival. In the sensitivity analysis, the respective hazard ratios for triplet therapy was HR 0.70 (95%CI 0.61-0.80) compared to docetaxel+ADT and 0.77 (95%CI 0.65-0.91) compared to androgen receptor pathway inhibitors +ADT combinations. It was estimated that there was 96% chance that one of the triplet therapy combinations were the best treatment option from an OS perspective. Triplet therapy also improved progression-free survival. These benefits were pronounced in men with high-volume disease burden and those with de novo metastatic disease.Conclusion: The finding suggest that triplet therapy is likely the most efficacious available option in men with metastatic, castration-sensitive prostate cancer, especially in those with high-volume disease burden. & COPY; 2022 Elsevier Inc. All rights reserved.