Background: AA and E improve overall survival (OS) in metastatic castration resistant prostate cancer (mCRPC). AA also improves OS in metastatic castration sensitive disease (mCSPC). However, concerns exist over the cost implications of earlier treatment versus the clinical benefit gained. We aimed to quantify and compare the clinical value of AA and E and their drug costs in both the mCRPC and mCSPC settings. Methods: We identified 6 randomized Phase 3 trials of AA and E in mCRPC and mCSPC. Net clinical benefit was quantified by the ASCO Value Framework version 2 (range < 180) and ESMO MCBS version 1.1 (range 1-5)—both consider benefits in overall survival, progression free survival, and quality of life, against increase in drug toxicity. A higher score indicates greater value. Incremental cancer drug costs were also calculated, using average wholesale price from the REDBOOK and the trials’ reported duration of treatment. Results: (Table). Conclusions: AA and E administered in early mCSPC do not provide consistent increases in net clinical benefit compared to mCRPC, but they incur exponential cost considerations. Alternatives such as chemotherapy, which may provide similar net clinical benefit at less incremental costs, still warrant major consideration for clinicians and patients. Until more information is available to define the optimal sequencing of AA, E and other available treatment modalities, current cost implications may hinder moving these agents to earlier treatment settings.

*Calculated with failure-free survival