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 castrationsensitive prostate cancer (mCSPC) has evolved rapidly over the past few years. Following publications of several large-scale randomized controlled trials (RCTs)Abiraterone (AA) andDocetaxel (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 was 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 meta-analysis to guide the selection of best first-line therapy for mCSPC. Method: 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 the random-effectsmodel under the 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 the highest P score of .85 for AA+ADT. For PFS, the HR ranged from 0.38 to 0.63. P Score is again highest at .38 for AA+ADT. As exploratory analyses, we compare the OS and PFS ofAA+ADT, ENZ+ADT, andAPA+ADT againstDOC+ADT. ForOS,HR for AA+ADT is 0.8 while HR for ENZ+ADT and APA +ADT are not statistically significant. For PFS, HR for both ENZ+ADT and AA+ADT is significant (0.62 and 0.61, respectively). AA+ADT has a higher P score than ENZ (.84 versus .81). Conclusions: Our findings suggest that AA + ADT appears to be more effective than APA-ADT, DOC + ADT, and ENZ+ADT 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.