COST-EFFECTIVENESS OF NOVEL ANDROGEN RECEPTOR INHIBITORS IN METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER: A U.S. ANALYSIS INCORPORATING TWO-WAY SENSITIVITY ASSESSMENT
Author(s)
William V. Padula, PhD1, Benjamin Cohen, MPH, PhD2, Paul G. Steel, MHS2, Bashir Kalayeh, PharmD, RPh3, Sreevalsa Appukkuttan, MPH3;
1University of Southern California, Los Angeles, CA, USA, 2Stage Analytics, Suwanee, GA, USA, 3Bayer, Whippany, NJ, USA
1University of Southern California, Los Angeles, CA, USA, 2Stage Analytics, Suwanee, GA, USA, 3Bayer, Whippany, NJ, USA
OBJECTIVES: Comparative effectiveness of androgen receptor pathway inhibitor (ARPI) plus androgen deprivation therapy (ADT) doublets in metastatic castration-sensitive prostate cancer (mCSPC) remains uncertain, and long-term economic studies in the United States (U.S.) are limited even though these regimens are preferred first-line options. A cost-effectiveness analysis showed darolutamide plus ADT (DAR+ADT) was cost-effective against enzalutamide plus ADT (ENZ+ADT) (ICER: $85,108) and dominated apalutamide plus ADT (APA+ADT) in progression-free mCSPC. This analysis extended these findings by evaluating cost-effectiveness under alternative assumptions for on-treatment and off-treatment health-state utilities in mCSPC.
METHODS: A partitioned survival model was developed from a U.S. healthcare sector perspective over a lifetime horizon. Progression-free and overall survival informed health-state occupancy (mCSPC, progressed disease, death), with comparative outcomes derived from a network meta-analysis. Direct medical costs (2025 USD) and QALYs were discounted at 3% annually, and incremental cost-effectiveness ratios (ICERs) were assessed at a $150,000/QALY threshold. Two-way sensitivity analyses explored the impact of assigning different utilities to the off-treatment mCSPC state while varying the relative baseline utilities of ENZ+ADT and APA+ADT compared with DAR+ADT.
RESULTS: DAR+ADT maintained cost-effectiveness across all plausible combinations of lower ENZ+ADT-treated utility values and increasing off-treatment disutility in the mCSPC state; under reasonable assumptions, the ICER fell as low as $10,722. DAR+ADT dominated APA+ADT in all plausible scenarios that combined reduced utility while on APA with additional off-treatment disutility.
CONCLUSIONS: DAR+ADT is a cost-effective first-line ARPI doublet for mCSPC, particularly when health-state utilities are varied to reflect differences in tolerability, discontinuation, and adverse events, supporting its QALY advantage relative to ENZ+ADT and APA+ADT. These findings may also translate into reduced caregiver strain, preserved productivity, and improved overall well-being that are not fully captured in conventional cost-effectiveness metrics. Novel value frameworks (e.g., GRACE) may better capture this broader value for patients and could support reassessing willingness-to-pay thresholds in metastatic prostate cancer.
METHODS: A partitioned survival model was developed from a U.S. healthcare sector perspective over a lifetime horizon. Progression-free and overall survival informed health-state occupancy (mCSPC, progressed disease, death), with comparative outcomes derived from a network meta-analysis. Direct medical costs (2025 USD) and QALYs were discounted at 3% annually, and incremental cost-effectiveness ratios (ICERs) were assessed at a $150,000/QALY threshold. Two-way sensitivity analyses explored the impact of assigning different utilities to the off-treatment mCSPC state while varying the relative baseline utilities of ENZ+ADT and APA+ADT compared with DAR+ADT.
RESULTS: DAR+ADT maintained cost-effectiveness across all plausible combinations of lower ENZ+ADT-treated utility values and increasing off-treatment disutility in the mCSPC state; under reasonable assumptions, the ICER fell as low as $10,722. DAR+ADT dominated APA+ADT in all plausible scenarios that combined reduced utility while on APA with additional off-treatment disutility.
CONCLUSIONS: DAR+ADT is a cost-effective first-line ARPI doublet for mCSPC, particularly when health-state utilities are varied to reflect differences in tolerability, discontinuation, and adverse events, supporting its QALY advantage relative to ENZ+ADT and APA+ADT. These findings may also translate into reduced caregiver strain, preserved productivity, and improved overall well-being that are not fully captured in conventional cost-effectiveness metrics. Novel value frameworks (e.g., GRACE) may better capture this broader value for patients and could support reassessing willingness-to-pay thresholds in metastatic prostate cancer.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
EE482
Topic
Economic Evaluation
Topic Subcategory
Novel & Social Elements of Value
Disease
SDC: Oncology