There was a high medical need for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) when several next-generation anti-androgens (apalutamide, enzalutamide, and darolutamide) demonstrated clinically relevant delays in metastasis onset. However, to date, few publications have assessed the pooled effect of these treatments on overall survival (OS). We performed a systematic review and meta-analysis of all randomized, placebo-controlled studies investigating a systemic treatment in nmCRPC. Publications were identified by searching several databases on April 7, 2021. The primary objective of this analysis was to determine the OS benefit. Secondary outcomes included the relative risk (RR) of adverse events (AEs) and grade 3-4 AEs. A sensitivity analysis with simulated data was also conducted to examine the influence of the study designs on the results. Three randomized controlled studies (SPARTAN, PROSPER, ARAMIS) met our inclusion criteria. Pooled meta-analyses showed a significant benefit in OS with the active agents versus placebo (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.65-0.83), as well as increased risk of any grade (RR 1.09, 95% CI 1.01-1.17) and grade 3-4 AEs (RR 1.50, 95% CI 1.23-1.83). The sensitivity analysis with SPARTAN-like simulated populations demonstrated that when using ARAMIS statistical design, OS would be statistically significant in 98.1% of the cases, at a shorter follow-up and with lower number of events. First-line treatment of nmCRPC patients with anti-androgens increased OS with an acceptable safety profile. In light of the different study designs and follow-up, results should be interpreted separately.
Clinical genitourinary cancer. 2021 Nov 21 [Epub]
Alejo Rodriguez-Vida, Andrés Rodríguez-Alonso, Eduardo Useros-Rodríguez, Fernando Lopez-Campos, Oscar Amor-Carro, Alberto Arribas-Ruiz, Javier Martinez-Torres, Javier Roca-Pardiñas, Alba Quesada-García, Jacobo R Muñoz-Del-Toro, Álvaro Juárez-Soto
Medical Oncology Department, Hospital del Mar, IMIM Research Institute, Barcelona, Spain. Electronic address: ., Urology Department, Complexo Universitario de Ferrol, Coruña, Spain., Urology Department, Infanta Elena University Hospital, Madrid, Spain., Radiation Oncology Department. Ramón y Cajal University Hospital, Madrid, Spain., Medical Affairs Department, Janssen, Madrid, Spain., Market Access, Janssen, Madrid, Spain., Applied Mathematics Department, University of Vigo, Vigo, Pontevedra, Spain., Statistics and Operational Research Department, University of Vigo, Vigo, Pontevedra, Spain., Urology Department, Jerez University Hospital, Cádiz, Spain.