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 by positive results from TITAN, ENZAMET and ARCHES studies. Both Apalutamide (APA) and Enzalutamide (EZA) have been shown to be superior to placebo (plus ADT) in mCSPC. However, no head to head comparison has been made for these four drugs in first line treatment. We therefore conducted a network metaanalysis to guide the selection of best first line therapy for mCSPC. Methods: A systematic review of RCTs of AA-/ADT-/APA-/DOC-/EZA-containing treatment regimens in newly diagnosed patients with mCSPC identified seven RCTs. (STAMPEDE arm C and arm G, CHARRTED, GETUG-AFU 15 and LATITUDE, TITAN, ENZAMET and ARCHES trials). We conducted a network 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 AAþADT. For PFS, the HR ranged between 0.38 to 0.63. P Score is again highest at 0.38 for AAþADT. As exploratory analyses, we compare the OS and PFS of AA þADT, ENZþADT and APAþADT against DOC þADT. For OS, HR for AAþADT is 0.8 while HR for ENZþADT and APA þADT are not statistically significant. For PFS, HR for both ENZþADT and AAþADT are significant (0.62 and 0.61 respectively). AAþADT has a higher P score than ENZ (0.84 versus 0.81). Conclusions: Our findings suggest that AA þ ADT appears to be more effective than APA-ADT, DOC þ ADT, and ENZþADT in reducing the risk of death in men with mCSPC and preventing disease progression. This network meta-analysis provides useful guidance to clinicians in choosing the first line therapy in mCSPC patients.