CONTEXT: Novel prospective randomized controlled observations addressing combination therapy in metastatic hormone-sensitive prostate cancer (mHSPC) have demonstrated promising overall survival (OS) outcomes. OBJECTIVE: To compare these novel findings and systematically review and address them within formal network meta-analyses (NMAs) that include observations from other prospective randomized controlled trials (RCTs). EVIDENCE ACQUISITION: First, we focused on abiraterone, enzalutamide, apalutamide, and docetaxel effects on OS in mHSPC using the PRISMA methodology. PubMed and abstracts identified prospective RCTs in first-line mHSPC. Second, we focused on mature studies that reached median OS and tested OS between abiraterone and docetaxel with tumor burden stratification. EVIDENCE SYNTHESIS: The first part included seven studies (n = 6639) and the second part, five studies (n = 4462). In the first part, abiraterone ranked first for high-volume mHSPC. Conversely, enzalutamide ranked first for low-volume mHSPC. In the second part, abiraterone treatment in high-volume mHSPC resulted in median OS of 50.1 mo and exceeded that with docetaxel (45.9 mo) and ADT alone (34.0 mo). Docetaxel treatment in low volume mHSPC resulted in median OS of 69.5 mo versus 67.7 mo with ADT alone. CONCLUSIONS: In conventional NMA that relied on conventional hazard ratios, differences were identified with respect to the relative efficacy of the combination therapies examined; abiraterone dominated the alternatives in high-volume mHSPC. In part two, which relied on trials for which median OS is available, comparison of abiraterone versus docetaxel revealed a 4-mo difference in OS in high-volume mHSPC. Conventional NMA may have overestimated the importance of treatment efficacy instead of focusing on median OS duration, which might represent a more important clinical endpoint. PATIENT SUMMARY: We reviewed studies on hormonal treatments and chemotherapy used for prostate cancer that has spread outside the prostate gland (metastatic prostate cancer, mPC). We found that the best overall survival was with the hormone agents abiraterone in high-volume mPC and enzalutamide in low-volume mPC. In comparison to the chemotherapy drug docetaxel, median overall survival with abiraterone was 4 months longer among patients with mPC.

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montreal Health Center Montreal QC Canada

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montreal Health Center Montreal QC Canada; Department of Neurosciences Reproductive Sciences and Odontostomatology University of Naples Federico 2 Naples Italy

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montreal Health Center Montreal QC Canada; Department of Urology and Division of Experimental Oncology Urological Research Institute IRCCS San Raffaele Scientific Institute Milan Italy

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montreal Health Center Montreal QC Canada; Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany

Department of Urology and Division of Experimental Oncology Urological Research Institute IRCCS San Raffaele Scientific Institute Milan Italy

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Weill Cornell Medical College New York NY USA; Department of Urology University of Texas Southwestern Dallas TX USA; Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic; Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia; Division of Urology Department of Special Surgery Jordan University Hospital The University of Jordan Amman Jordan

Department of Urology University Hospital Frankfurt Frankfurt am Main Germany

Department of Urology University Hospital Frankfurt Frankfurt am Main Germany; Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montreal Health Center Montreal QC Canada

Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany

Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany; Department of Urology University Hospital Hamburg Eppendorf Hamburg Germany

Citace poskytuje Crossref.org

Overall survival and adverse events after treatment with darolutamide vs. apalutamide vs. enzalutamide for high-risk non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis