First-line Therapy for Metastatic Castration-sensitive Prostate Cancer: a Network Meta-analysis

Abstract

Objective: The treatment landscape of metastatic castration-sensitive prostate cancer (mCSPC) has been transforming in the past decade. Abiraterone acetate plus prednisolone (AAP), apalutamide (APA), enzalutamide (ENZA), and docetaxel (Doce) added to androgen deprivation therapy (ADT) were shown to outperform ADT alone. However, data on direct comparison of the different regimens are sparse. We sought to review current evidence on first-line therapies in mCSPC and compare their results in terms of overall survival (OS) and progression-free survival (PFS) in a network meta-analysis. Methods: We performed a systematic search of PubMed, MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and Cochrane Library databases in September 2020. ADT was the reference category. Treatments were grouped into four categories: Doce+ADT, AAP+ADT, APA+ADT, and ENZA+ADT. The primary endpoint of our study was OS. Results: We analysed eight trials with 7790 total patients, using frequentist network meta-analysis and P-score to rank the treatments. AAP+ADT showed the highest P-score of 86% with a hazard ratio (HR) of 0.63 (95% confidence interval [CI]=0.56-0.71) in OS while ENZA+ADT performed best in PFS (HR=0.40, 95% CI=0.34-0.46) with a P-score of 98%. Conclusion: We found that AAP+ADT treatment was most effective in prolonging OS. ENZA+ADT might provide better PFS in mCSPC. Analysis of OS and PFS provides guidance on selecting the best choice of first-line treatments.