Cost-effectiveness of adding enzalutamide vs standard non-steroidal antiandrogen drugs for patients with metastatic hormone-sensitive prostate cancer undergoing standard first-line therapy: a within-trial, secondary end-point analysis of the ENZAMET phase 3, international randomized trial (ANZUP 1304).

Background: The ENZAMET randomized trial demonstrated adding enzalutamide to testosterone suppression, compared with a less potent comparator, significantly improved overall and progression-free survival in men with metastatic hormone-sensitive prostate cancer (mHSPC). This study evaluated cost-effectiveness of adding enzalutamide to standard therapy over 60 months. Methods: A within-trial cost-effectiveness analysis was conducted from an Australian health system perspective using prospectively collected, observed data from ENZAMET open-label, phase 3 RCT. This study is registered with ClinicalTrials.gov, NCT02446405, ANZCTR, ACTRN12614000110684, and EudraCT, 2014-003190-42. The analysis was conducted utilizing a data cut-off date of January 19, 2022, with a median follow-up of 68 months. Information on disease status, healthcare utilization, and health-related quality of life were extracted from trial records, linked Medicare claims and patient questionnaires. Costs were calculated in 2023 Australian dollars. EQ-5D-5L scores were converted to health utilities using a validated algorithm. Quality-adjusted life years (QALYs) were estimated by multiplying mean health utility with corresponding life-years accumulated. Deterministic and probabilistic sensitivity analyses examined the effect of varying unit price of study drugs, per diem rates of hospital stays, benefits paid from Medicare claims, and health utility values on robustness of results. Data were assessed for missingness and imputation applied where relevant. Findings: Enzalutamide was associated with an additional AUD$127,262 per patient in healthcare costs, 0.24 life-years and 0.15 QALYs gained in the first 5 years, compared with non-steroidal antiandrogen therapy. The incremental cost-effectiveness ratio, (ICER) was AUD$543,880 per life-year gained and AUD$835,580 per QALY gained. Results were sensitive to the cost of study drug, with a purchase price of AUD$6.73 per tablet yielding an ICER that met the willingness-to-pay threshold of AUD$50,000 per QALY gained. Of note, hospitalizations were slightly higher in the enzalutamide group; as was use of musculoskeletal medicines, the latter indicating falls and fractures. Interpretation: Although Enzalutamide improves quality-adjusted survival for men with mHSPC, it is unlikely to be cost-effective. Long-term bone health management in survivors is an important clinical consideration. Funding: Astellas Pharma and Australian National Health and Medical Research Council.