What is the best first-line therapy for metastatic castration-sensitive prostate cancer in 2019? A network meta-analysis

Abstract

Background: The treatment landscape of metastatic castration-sensitive prostate cancer (mCSPC) has evolved rapidly over past few years. Following publications of several large-scale randomised controlled trials (RCTs) Abiraterone (AA) and Docetaxel (DOC), in addition to androgen deprivation therapy (ADT) have been approved as first line therapies for high risk and high volume mCSPC respectively. In 2019, the picture is further complicated bypositiveresults from TITAN, ENZAMET and ARCHES studies. Both Apalutamide (APA) and Enzalutamide (EZA) have been shown to besuperior to placebo (plus ADT) in mCSPC. However, nohead to head comparison has been made for these four drugs in first line treatment. We therefore conducted a network meta-analysis to guide the selection of best first line therapy for mCSPC. Methods: A systematic reviewofRCTs of AA-/ADT-/APA-/DOC-/EZA-containing treatment regimens in newly diagnosed patients with mCSPC identified seven RCTs. (STAMPEDEarmCand armG,CHARRTED,GETUG-AFU15and LATITUDE, TITAN, ENZAMET and ARCHES trials). We conductedanetwork meta-analysis with random-effects model under frequentist framework. The reported hazard ratios for overall survival (OS) and progression-free survival (PFS) were incorporated into the model. We used P score to rank the treatments. Treatments having higher P scores are suggested to be more preferred. Results: Comparing with ADT alone, the hazard ratio (HR) for OS ranged from 0.62 to 0.77 with a highest P score of 0.85 for AA+ADT. For PFS, the HR ranged between 0.38 to 0.63. P Score is again highest at 0.38 for AA+ADT. As exploratory analyses, wecompare theOSand PFSofAA+ADT, ENZ+ADT and APA+ADT against DOC +ADT.For OS, HR for AA+ADTis0.8 whileHRfor ENZ+ADT and APA +ADT are not statistically significant. For PFS,HRforboth ENZ+ADT and AA+ADT are significant(0.62 and0.61 respectively). AA+ADT has a higher P score than ENZ (0.84 versus 0.81). Conclusions: Our findings suggest that AA + ADT appears to be more effective than APA-ADT, DOC+ADT, and ENZ+ADT in reducing the riskofdeath inmen with mCSPC and preventing disease progression. This network meta-analysis provides useful guidance to clinicians in choosing the first line therapy in mCSPC patients.