Systematic Review of Efficacy and Health Economic Implications of Real-world Treatment Sequencing in Prostate Cancer: Where Do the Newer Agents Enzalutamide and Abiraterone Fit in?

CONTEXT: Optimal treatment sequencing of abiraterone and enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) is challenging. Real-world data (RWD) allow a better understanding of health economic implications in the real world. OBJECTIVE: To determine survival and cost outcomes for two real-world treatment sequences, comparing abiraterone to enzalutamide (AA → ENZ) with enzalutamide to abiraterone (ENZ → AA). EVIDENCE ACQUISITION: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Searches were performed in Medline, Embase, and Web of Science. EVIDENCE SYNTHESIS: Seventeen studies met our inclusion criteria. Of studies with survival outcomes, 10 featured AA → ENZ treatment sequences (n = 575), four ENZ → AA sequences (n = 205), and three both sequences. Better survival outcomes were demonstrated in the AA → ENZ cohorts in several studies reporting prostate-specific antigen (PSA) progression-free survival (PSA-PFS), combined PSA-PFS, and PSA decline ≥50%. Three studies showed shorter treatment duration in cohorts receiving second-line enzalutamide compared with abiraterone. Collectively, six RWD costing studies described patients with mCRPC who experienced treatment with enzalutamide (n = 4195), abiraterone (n = 10 372), AA → ENZ (n = 443), and ENZ → AA (n = 91). No study estimated the cost of treatment sequencing of AA → ENZ or ENZ → AA. CONCLUSIONS: No head-to-head studies were found, but we hypothesise that the AA → ENZ sequence may be less costly than ENZ → AA, because time on treatment tends to be longer for a first-line treatment and abiraterone is less costly than enzalutamide. There are indications that PFS of AA → ENZ is superior to that of ENZ → AA, which supports the former sequence as more cost-effective. PATIENT SUMMARY: Better survival outcomes were reported in several studies where patients with advanced prostate cancer received the abiraterone to enzalutamide sequence compared with the enzalutamide to abiraterone sequence. No study estimated the cost of sequencing either treatment approach.