Within-trial hospitalization resource utilization and budget impact analysis for darolutamide in metastatic hormone-sensitive prostate cancer using ARASENS.

BACKGROUND: ARASENS was a randomized, double-blind, phase 3 trial comparing darolutamide + docetaxel + androgen deprivation therapy (ADT) with placebo + docetaxel + ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC). OBJECTIVE: To use clinical trial data from ARASENS to understand whether the addition of darolutamide to docetaxel + ADT leads to increased hospitalizations and to estimate the budget impact on the US health care system. METHODS: We used mixed-effects negative binomial regression to estimate hospitalization and intensive care unit (ICU) admission rates and length of hospital stay (LoHS) counts. Hospitalization rates were estimated per treatment arm for the period during and after administration of docetaxel. Based on these estimates, a budget impact analysis evaluated the hospitalization costs (including ICU admissions) and standalone ICU hospitalization costs for the totality of the US population over a 5-year time horizon. The analysis compared a scenario without darolutamide vs one with darolutamide included in the US payer formulary. Hospitalization estimates were varied in a one-way sensitivity analysis. RESULTS: The first 4 months of treatment (when patients were receiving docetaxel) were associated with increased hospitalizations across both arms. The addition of darolutamide was associated with a numerical reduction in the rate of hospitalization (per year) due to any reason both during docetaxel treatment (1.01 visits per year [95% CI = 0.82-1.20] vs 1.18 visits per year [95% CI = 0.96-1.41]) and after docetaxel treatment (0.28 visits per year [95% CI = 0.23-0.34] vs 0.33 visits per year [95% CI = 0.27-0.40]). Darolutamide was associated with a marginally longer LoHS per hospitalization compared with placebo (+1.90 days per year) both during and after docetaxel treatment. ICU admissions were low in the ARASENS data; admission rates were assumed to be the same during and after docetaxel treatment. ICU admission rate estimates were equivalent across arms (0.02 visits per year [95% CI = 0.01-0.03]). The budget impact per treated member per month represents a cost-neutral option after Year 5 with a cumulative budget impact of -$9.71. CONCLUSIONS: The addition of darolutamide to docetaxel + ADT was associated with a numerically lower rate of hospitalization but marginally longer LoHS compared with docetaxel + ADT alone. Darolutamide represents a cost-neutral alternative per treated member per month compared with docetaxel + ADT with regard to hospitalizations at the end of a 5-year time horizon.

Real-world treatment of metastatic hormone-sensitive prostate cancer in the USA, Europe and Asia.

Aim: To characterize real-world patients with metastatic hormone-sensitive prostate cancer (mHSPC) and treating physicians and evaluate treatment trends and baseline concordance versus guidelines internationally. Materials & methods: Retrospective, cross-sectional data from the Ipsos Global Oncology Monitor database 2018-2020 were used for descriptive analysis of mHSPC patients, treating physicians and treatment utilization. Results: Among the 6198 mHSPC patients from five countries, the most common treatment was either androgen deprivation therapy (ADT) monotherapy or first-generation androgen receptor inhibitor + ADT. Second-generation androgen receptor inhibitor use was only initiating but increasing over the study period. Conclusion: Despite contemporaneous guidelines recommending treatment intensification of ADT in combination with novel antihormonals or docetaxel, 76.1% of reported mHSPC patients received non-guideline-concordant care.

Prostate cancer is the second most common cancer among men worldwide and a leading cause of cancer-related death globally. Metastatic hormone-sensitive prostate cancer (mHSPC) refers to the stage of prostate cancer where it has spread to other parts of the body ('metastatic') but still responds to hormonal therapy ('hormone-sensitive'), such as androgen deprivation therapy (ADT). Treatment guidelines around the world for men with mHSPC have changed over time, but there remains a lack of understanding of how well guidelines are followed in real-world practice. Consequently, this study analyzes real-world data from five countries between 2018 and 2020 to understand treatment patterns, baseline concordance versus guidelines and potential drivers of treatment trends. The study found prevalent use of ADT monotherapy and older antihormonal agents, and only marginal but increasing use of novel antihormonals in real-world practice. These practices deviate from guidelines from the study period, which generally recommended ADT combination with either newer antihormonal agents or docetaxel for patients with mHSPC. Overall, the proportion of the 6198 patients treated with non­guideline-concordant therapies was 76.1%. Since guideline-recommended care is associated with better outcomes, this baselining finding highlights the need for appropriate treatment selection and intensification for mHSPC patients.

The Health Inequality Impact of a New Cancer Therapy Given Treatment and Disease Characteristics.

OBJECTIVES: This study aimed to perform a simulation study to quantify the health inequality impact of a cancer therapy given cancer and treatment characteristics using the distributional cost-effectiveness framework. METHODS: The following factors were varied in 10 000 simulations: lifetime risk of the disease, median overall survival (OS) with standard of care (SOC), difference in OS between non-Hispanic (NH)-Black and NH-White patients (prognostic effect), treatment effect of the new therapy relative to SOC, whether the treatment effect differs between NH-Black and NH-White patients (effect modification), health utility, drug costs, and preprogression and postprogression costs. Based on these characteristics, the incremental population net health benefits were calculated for the new therapy and applied to a US distribution of quality-adjusted life expectancy at birth. The health inequality impact was quantified as the difference in the degree of inequality in the "post-new therapy" versus "pre-new therapy" quality-adjusted life expectancy distributions. RESULTS: For cancer types characterized by relatively large lifetime risk, large median OS with SOC, large treatment effect, and large effect modification, the direction of the impact of the new therapy on inequality is easy to predict. When effect modification is minor or absent, which is a realistic scenario, the direction of the inequality impact is difficult to predict. Larger incremental drug costs have a worsening effect on health inequality. CONCLUSIONS: The findings provide a guide to help decision makers and other stakeholders make an initial assessment whether a new therapy with known treatment effects for a specific tumor type can have a positive or negative health inequality impact.

Survival Outcomes by Race and Ethnicity in Veterans With Nonmetastatic Castration-Resistant Prostate Cancer.

Importance: Racial and ethnic disparities in prostate cancer are poorly understood. A given disparity-related factor may affect outcomes differently at each point along the highly variable trajectory of the disease. Objective: To examine clinical outcomes by race and ethnicity in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) within the US Veterans Health Administration. Design, Setting, and Participants: A retrospective, observational cohort study using electronic health care records (January 1, 2006, to December 31, 2021) in a nationwide equal-access health care system was conducted. Mean (SD) follow-up time was 4.3 (3.3) years. Patients included in the analysis were diagnosed with prostate cancer from January 1, 2006, to December 30, 2020, that progressed to nmCRPC defined by (1) increasing prostate-specific antigen levels, (2) ongoing androgen deprivation, and (3) no evidence of metastatic disease. Patients with metastatic disease or death within the landmark period (3 months after the first nmCRPC evidence) were excluded. Main Outcomes and Measures: The primary outcome was time from the landmark period to death or metastasis; the secondary outcome was overall survival. A multivariate Cox proportional hazards model, Kaplan-Meier estimates, and adjusted survival curves were used to evaluate outcome differences by race and ethnicity. Results: Of 12 992 patients in the cohort, 826 patients identified as Hispanic (6%), 3671 as non-Hispanic Black (28%; henceforth Black), 7323 as non-Hispanic White (56%; henceforth White), and 1172 of other race and ethnicity (9%; henceforth other, including American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, unknown by patient, and patient declined to answer). Median time elapsed from nmCRPC to metastasis or death was 5.96 (95% CI, 5.58-6.34) years for Black patients, 5.62 (95% CI, 5.11-6.67) years for Hispanic patients, 4.11 (95% CI, 3.96-4.25) years for White patients, and 3.59 (95% CI, 3.23-3.97) years for other patients. Median unadjusted overall survival was 6.26 (95% CI, 6.03-6.46) years among all patients, 8.36 (95% CI, 8.0-8.8) years for Black patients, 8.56 (95% CI, 7.3-9.7) years for Hispanic patients, 5.48 (95% CI, 5.2-5.7) years for White patients, and 4.48 (95% CI, 4.1-5.0) years for other patients. Conclusions and Relevance: The findings of this cohort study of patients with nmCRPC suggest that differences in outcomes by race and ethnicity exist; in addition, Black and Hispanic men may have considerably improved outcomes when treated in an equal-access setting.

Safety differences across androgen receptor inhibitors in nonmetastatic castration-resistant prostate cancer.

Approval of apalutamide, enzalutamide and darolutamide has transformed the treatment landscape and guideline recommendations for patients with nonmetastatic castration-resistant prostate cancer but now raises the issue of decision-making regarding treatment selection. In this perspective, we discuss the efficacy and safety of these second-generation androgen receptor inhibitors and propose that for patients with nonmetastatic castration-resistant prostate cancer, safety considerations for these treatments are especially important. We examine these considerations in the context of patient and caregiver preferences as well as patient clinical characteristics. We further posit that consideration of treatments' safety profiles should include not only the initial direct impacts from potential treatment-emergent adverse events and drug-drug interaction events, but also the full cascade of potentially avoidable healthcare complications.

Prostate cancer is one of the most common cancers in men. Because male hormones fuel the growth of prostate cancer cells, initial treatments generally focus on reducing these hormones to very low levels. Although these treatments are usually effective in controlling the cancer in the short term, over time, patients often stop responding to them. These patients need more advanced treatments to control their prostate cancer. For patients whose cancer has not spread to other body parts ('nonmetastatic castration-resistant prostate cancer'), more advanced treatment options were unavailable until recently, but during 2018­2019, three novel therapies became available. These new therapies have raised the question of how to choose a particular therapy when deciding on a patient's treatment regimen. Here we contend that patient safety is critical when deciding among these treatments, which are all similarly effective in terms of helping patients to live longer. We review the key differences of each drug's safety profile among these treatments. We assert that treatment selection should consider patients' preferences and clinical characteristics, as the latter can influence the potential for serious harm when treatment-related complications arise. Finally, treatment selection should consider the multiple after-effects that can occur following a treatment-related safety event.