Budget impact analysis of darolutamide for treatment of nonmetastatic castration-resistant prostate cancer.

BACKGROUND: Darolutamide, a structurally distinct androgen receptor inhibitor approved for the treatment of men with nonmetastatic castration-resistant prostate cancer (nmCRPC), has been shown to increase metastasis-free survival among men with nmCRPC compared with placebo. This treatment has a novel chemical structure that may also have safety, tolerability, and efficacy advantages for men with nmCRPC. OBJECTIVE: To estimate the projected budget impact of including darolutamide on a U.S. payer formulary as a treatment option for men with nmCRPC. METHODS: A budget impact model was developed to evaluate darolutamide for nmCRPC for a hypothetical 1-million-member plan over a 5-year period. Costs (drug acquisition, drug administration, and treatment-related adverse events [AEs]) were estimated for 2 scenarios: with and without darolutamide treatment for nmCRPC. The budget impact of darolutamide was calculated as the difference in costs for these 2 scenarios. An analysis for high-risk nmCRPC also was conducted. The model included treatments recommended by the National Comprehensive Cancer Network (e.g., apalutamide and enzalutamide) and potential comparators that are used but are not specifically indicated for nmCRPC. All treatments were assumed to be administered in combination with a weighted average androgen deprivation therapy comparator (consisting of luteinizing hormone-releasing hormone [LHRH] agonists, LHRH antagonists, and first-generation antiandrogens). Market share estimates were derived from interviews with physicians treating men with nmCRPC. The model includes grade 3-4 AEs, and the rates were obtained from clinical trial data. Costs were taken from publicly available sources and varied in a one-way sensitivity analysis. RESULTS: For a plan with 1 million lives, there were approximately 90 incident cases of nmCRPC (46 high risk) each year, with 332 (109 high risk) treatment-eligible cases by year 5. Darolutamide's market share increased from 3.6% in year 1 to 18% in year 5. Given the utilization of other agents, introducing darolutamide along with other targeted therapies was predicted to increase the total budget by $158,640 ($0.0132 per member per month [PMPM]) in year 1, which decreased over time to a cost savings of $149,240 ($0.0124 PMPM) by year 5. The scenario with darolutamide showed reduced AE costs each year. Similar results were observed for the high-risk nmCRPC population. CONCLUSIONS: Adding darolutamide to a U.S. payer formulary for the treatment of nmCRPC can result in a manageable increase in the budget that is partly offset by AE costs in the first 4 years, followed by a cost savings by year 5. DISCLOSURES: This study was conducted by RTI Health Solutions under the direction of Bayer U.S. and was funded by Bayer U.S., which was involved in the design of the study; collection, analysis, and interpretation of the data; writing of the report; and the decision to submit the report for publication. Miles and Purser (and/or their institutions) are employees of RTI Health Solutions and received research funding from Bayer U.S. to develop the budget impact model. Appukkuttan and Farej are employees of Bayer U.S. Wen was an employee of Bayer U.S. at the time of the study. This study was presented as a poster at the AMCP Virtual Learning Event, April 20-24, 2020.

Sipuleucel-T for the Treatment of Metastatic Hormone-Relapsed Prostate Cancer: A NICE Single Technology Appraisal; An Evidence Review Group Perspective.

The National Institute for Health and Care Excellence (NICE) invited Dendreon, the company manufacturing sipuleucel-T, to submit evidence for the clinical and cost effectiveness of sipuleucel-T for asymptomatic or minimally symptomatic, metastatic, non-visceral hormone-relapsed prostate cancer patients in whom chemotherapy is not yet clinically indicated, as part of NICE's single technology appraisal process. The comparator was abiraterone acetate (AA) or best supportive care (BSC). The School of Health and Related Research at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG). This paper describes the company submission (CS), ERG review, and subsequent decision of the NICE Appraisal Committee (AC). The ERG produced a critical review of the clinical and cost-effectiveness evidence of sipuleucel-T based upon the CS. Clinical-effectiveness data relevant to the decision problem were taken from three randomised controlled trials (RCTs) of sipuleucel-T and a placebo (PBO) comparator of antigen-presenting cells (APC) being re-infused (APC-PBO) (D9901, D9902A and D9902B), and one RCT (COU-AA-302) of AA plus prednisone vs. PBO plus prednisone. Two trials reported a significant advantage for sipuleucel-T in median overall survival compared with APC-PBO: for trial D9901, an adjusted hazard ratio (HR) 0.47; (95 % confidence interval [CI] 0.29, 0.76) p < 0.002; for D9902B, adjusted HR 0.78 (95 % CI 0.61, 0.98) p = 0.03. There was no significant difference between groups in D9902A, unadjusted HR 0.79 (95 % CI 0.48, 1.28) p = 0.331. Sipuleucel-T and APC-PBO groups did not differ significantly in time to disease progression, in any of the three RCTs. Most adverse events developed within 1 day of the infusion, and resolved within 2 days. The CS included an indirect comparison of sipuleucel-T (D9902B) and AA plus prednisone (COU-AA-302). As trials differed in prior use of chemotherapy, an analysis of only chemotherapy-naïve patients was included, in which the overall survival for sipuleucel-T and AA was not significantly different, HR 0.94 (95 % CI 0.69, 1.28) p = 0.699. The ERG had several concerns regarding the data and assumptions incorporated within the company's cost-effectiveness analyses and conducted exploratory analyses to quantify the impact of making alternative assumptions or using alternative data inputs. The deterministic incremental cost-effectiveness ratio (ICER) for sipuleucel-T vs. BSC when using the ERG's preferred data and assumptions was £ 108,585 per quality-adjusted life-year (QALY) in the whole licensed population and £ 61,204/QALY in the subgroup with low prostate-specific antigen at baseline. The ERG also conducted an incremental analysis comparing sipuleucel-T with both AA and BSC in the chemotherapy-naïve subgroup. Sipuleucel-T had a deterministic ICER of £ 111,682/QALY in this subgroup, when using the ERG's preferred assumptions, and AA was extendedly dominated. The ERG also concluded that estimates of costs and benefits for AA should be interpreted with caution given the limitations of the indirect comparison. The AC noted that the ICER for sipuleucel-T was well above the range usually considered cost effective, and did not recommend sipuleucel-T for the treatment of asymptomatic or minimally symptomatic, metastatic, non-visceral hormone-relapsed prostate cancer.