Cost-Utility Analysis of Darolutamide Combined with Androgen Deprivation Therapy for Patients with High-Risk Non-Metastatic Castration-Resistant Prostate Cancer in China.

INTRODUCTION: The increasing incidence of prostate cancer (PC) in China leads to a significant disease burden. Although three novel androgen inhibitors (darolutamide, apalutamide, and enzalutamide) have been approved for patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC), the economic evaluation of these novel treatments in China remains unknown. In this study, we aimed to evaluate the cost-utility of darolutamide combined with androgen deprivation therapy (ADT), comparing with apalutamide + ADT and enzalutamide + ADT, in patients with high-risk nmCRPC from a healthcare system perspective in China. METHODS: A partitioned survival model was developed to capture time spent by patients in three health states: nmCRPC, metastatic CRPC (mCRPC), and death. Clinical outcomes from the ARAMIS, PROSPER, and SPARTAN studies were obtained. In the absence of head-to-head studies, indirect treatment comparisons were conducted to capture the comparative effectiveness between darolutamide + ADT, apalutamide + ADT, and enzalutamide + ADT. The prices of apalutamide and enzalutamide were assumed to be the same as the initial launch price of darolutamide, since post-negotiation prices after national reimbursement drug list (NRDL) inclusion remain confidential. Other health resources costs, baseline characteristics, treatment patterns, and utility were collected through literature or clinical expert interviews. Selected sensitivity analyses were also performed. RESULTS: For a 20-year time horizon, darolutamide + ADT was associated with lower cost per quality-adjusted life years (QALYs) than apalutamide + ADT and enzalutamide + ADT (202,897 Chinese yuan (CNY)/QALY vs. 228,998 CNY/QALY and 221,409 CNY/QALY, respectively) (exchange rate, 1 USD = 6.7871 CNY). Darolutamide + ADT had better health outcomes and lower total costs compared to both apalutamide + ADT (+ 0.22 QALYs and - 72,818 CNY) and enzalutamide + ADT (+ 0.09 QALYs and - 67,451 CNY). Across the modelled sensitivity analyses (including hazard ratios and drug costs), darolutamide + ADT remained dominant or cost-effective. CONCLUSIONS: This economic evaluation suggested that, in comparison with apalutamide + ADT and enzalutamide + ADT, darolutamide + ADT was a dominant or cost-effective treatment option for patients with high-risk nmCRPC in China.

Real-world burden of adverse events for apalutamide- or enzalutamide-treated non-metastatic castration-resistant prostate cancer patients in the United States.

BACKGROUND: Second-generation androgen receptor inhibitors (ARIs) have been associated with adverse events (AEs) such as fatigue, falls, fractures, and rash in non-metastatic castration-resistant prostate cancer (nmCRPC) patients as identified in clinical trials. The objectives of this study were to describe the incidence and management of AEs in patients receiving apalutamide and enzalutamide. METHODS: This retrospective chart review study was conducted in nmCRPC-treating sites in the United States. Patients starting apalutamide or enzalutamide between February 1, 2018 and December 31, 2018 were included and any AEs they experienced were recorded. AEs, including those considered to be of special interest as defined in the pivotal clinical trials of the second-generation ARIs, were analyzed and grouped retrospectively in this study. Detailed chart data (patient demographics, clinical characteristics, treatment history, type of AE, outcomes, and resource utilization) were then collected for a randomly selected subset among patients with ≥1 AE to characterize AEs and their management. Descriptive results were summarized. RESULTS: Forty-three sites participated in the study. A total of 699 patients were included, of whom 525 (75.1%) experienced ≥1 AE. The most common AEs were fatigue/asthenia (34.3%), hot flush (13.9%), and arthralgia (13.6%). In the subset of 250 patients randomly selected from those who experienced ≥1 AE, patients were primarily White (72.0%), the mean age was 71 years, 86.0% had an Eastern Cooperative Oncology Group score of 0-1 at nmCRPC diagnosis, and the average prostate specific antigen (PSA) value at diagnosis was 23.2 ng/mL. PSA-doubling time < 10 months was chosen as reason to initiate treatment in 40% of patients. The median duration of follow-up was 1.1 years, with 14.4% of patients progressing to metastasis by end of study period. Grade 3-4 and Grade 5 AEs occurred in 14.4 and 0.4% of patients, respectively. Actions taken to manage AEs included AE-directed treatment (38.0%), ARI discontinuation (10.4%), dose reduction (7.6%), and AE-related hospitalization (4.8%). CONCLUSIONS: This study highlights the burden of AEs among nmCRPC patients treated with apalutamide or enzalutamide, providing a relevant real-world benchmark as clinical trial evidence and the treatment landcape for nmCRPC continues to evolve.

Real-world incidence and burden of adverse events among non-metastatic prostate cancer patients treated with secondary hormonal therapies following androgen deprivation therapy.

Aims: To describe the incidence and identify prognostic factors of central nervous system (CNS) adverse events (AEs) and any AEs (CNS, skin rash, or fracture) and evaluate the healthcare resource utilization (HCRU), direct medical costs, and therapy discontinuation associated with these AEs among non-metastatic prostate cancer (nmPC) patients who received secondary hormone therapies.Methods and results: nmPC patients who had initiated secondary hormonal therapy with enzalutamide, bicalutamide, or abiraterone ≥1 year after androgen deprivation therapy (ADT) were identified in the MarketScan database. Survival analyses were used to describe the incidence of CNS or any AEs. Annual HCRU and costs were compared across patient groups (CNS AE vs no CNS AE; any AE vs no AE) using propensity score weighted generalized linear models. Multivariate Cox proportional hazards models were used to identify AE predictors and compare risks of discontinuation.Results: The analysis included 532 patients who initiated secondary hormonal therapies, among whom 201 (38%) and 244 (46%) experienced a CNS AE and any AE, respectively. Median times to CNS AE and any AE from therapy initiation were 17.90 and 11.00 months, respectively. Predictors of any AE were any AE in the baseline period (≤6 months before starting therapy), Charlson Comorbidity Index (CCI) score (1 vs 0), surgical castration, and older age. Predictors of CNS AEs were CNS AE in the baseline period and CCI score (1 vs 0). CNS and any AEs were associated with significantly higher HCRU. CNS AEs were associated with significantly higher incremental total medical costs ($18,522). CNS AEs and any AEs significantly increased therapy discontinuation risk by 48% and 38%, respectively.Conclusions: AEs increase the economic burden and therapy discontinuation among nmPC patients receiving secondary hormonal therapies subsequent to ADTs. These patients should be carefully evaluated for AEs to reduce therapy discontinuation, HCRU, and direct medical costs.