Costs of radium-223 and the pharmacy preparation 177Lu-PSMA-I&T for metastatic castration-resistant prostate cancer in Dutch hospitals.

OBJECTIVE: The radiopharmaceuticals radium-223 and the pharmacy preparation 177Lu-PSMA-I&T are reimbursed in the Netherlands for metastatic castration-resistant prostate cancer (mCRPC) treatment. Although shown to be life-prolonging in patients with mCRPC, the treatment procedures associated with these radiopharmaceuticals can be challenging for both patients and hospitals. This study investigates the costs of mCRPC treatment in Dutch hospitals for currently reimbursed radiopharmaceuticals with a demonstrated overall survival benefit. METHODS: A cost model that calculated the direct medical per-patient costs of radium-223 and 177Lu-PSMA-I&T was developed, following clinical trial regimens. The model considered six 4-weekly administrations (i.e. ALSYMPCA regimen) of radium-223. Regarding 177Lu-PSMA-I&T, the model used both the VISION regimen (i.e. five 6-weekly administrations) and the SPLASH regimen (i.e. four 8-weekly administrations). Based on health insurance claims, we also estimated the coverage a hospital would receive for providing treatment. No fitting health insurance claim for 177Lu-PSMA-I&T is currently available; therefore, we calculated a break-even value for a potential health insurance claim that would exactly counterbalance the per-patient costs and coverage. RESULTS: Radium-223 administration is associated with per-patient costs of €30,905, and these costs are fully covered by the coverage a hospital receives. The per-patient costs of 177Lu-PSMA-I&T range between €35,866 and €47,546 per administration period, depending on the regimen. Current healthcare insurance claims do not fully cover the costs of providing 177Lu-PSMA-I&T: hospitals must pay €4,414-€4,922 for each patient out of their own budget. The break-even value for the potential insurance claim covering 177Lu-PSMA-I&T administration with a VISION (SPLASH) regimen is €1,073 (€1,215). CONCLUSION: This study shows that, without consideration of the treatment effect, radium-223 treatment for mCRPC leads to lower per-patient costs than treatment with 177Lu-PSMA-I&T. The detailed overview of the costs associated with radiopharmaceutical treatment provided by this study is relevant for both hospitals and healthcare insurers.

Prostate cancer is the most common form of cancer among men in the Netherlands, and its treatment is increasingly expensive. Given the limited hospital budget, it is important to consider costs in the treatment of prostate cancer. Radiopharmaceuticals are one of the multiple treatment options for metastatic prostate cancer. The current study looked at the costs of two radiopharmaceuticals, radium-223 and 177Lu-PSMA-I&T, while using multiple treatment regimens.The cost of radium-223 treatment is €30,905 per patient and is fully covered by insurance. The cost of 177Lu-PSMA-I&T treatment ranges from €35,866 to €47,546 per patient and is partially paid from the budget of the hospitals considering current reimbursement amounts. The study shows that, without consideration of the treatment effects, radium-223 treatment for prostate cancer leads to lower per-patient costs than treatment with 177Lu-PSMA-I&T. The detailed overview of the costs associated with radiopharmaceutical treatment provided by this study is relevant for both hospitals and healthcare insurers to manage prostate cancer treatment costs.

Cost-effectiveness analysis of enzalutamide for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer in Japan.

BACKGROUND: We aimed to evaluate cost-effectiveness of enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer patients in Japan. METHODS: A Markov model was developed to capture time spent by patients in various health states: stable, progression and death. Abiraterone acetate and docetaxel were set as active comparators. Clinical outcomes were obtained from the PREVAIL, COU-AA-302 and TAX327 trials. Treatment sequence, concomitant drugs and therapies for adverse events were estimated from responses to a survey by 14 Japanese prostate cancer experts. The analytic perspective was public healthcare payer, with a 10-year time horizon. The incremental cost-effectiveness ratio was estimated from quality-adjusted life-years and Japanese public healthcare costs. Probabilistic sensitivity analysis was performed to assess the robustness of the findings. RESULTS: According to the survey, the most common treatment sequences were (i) enzalutamide â†’ docetaxel â†’ cabazitaxel (enzalutamide-first sequencing), (ii) abiraterone â†’ enzalutamide â†’ docetaxel (abiraterone-first sequencing) and (iii) docetaxel→ enzalutamide â†’ cabazitaxel (docetaxel-first sequencing). In the base-case analysis, enzalutamide-first sequencing saved 1.74 million Japanese Yen versus abiraterone-first sequencing, with a 0.129 quality-adjusted life-year gain (dominant). Enzalutamide-first sequencing had a cost increase of 4.44 million Japanese Yen over docetaxel-first sequencing, with a 0.371 quality-adjusted life-years gain. The incremental cost-effectiveness ratio of enzalutamide-first sequencing versus docetaxel-first sequencing was estimated as 11.94 million Japanese Yen/quality-adjusted life-years. Probabilistic sensitivity analyses demonstrated that, compared with abiraterone-first sequencing, enzalutamide-first sequencing had an 87.4% probability of being dominant. CONCLUSIONS: Results modeled herein suggest that the enzalutamide-first sequencing is more cost-effective than the abiraterone-first sequencing, but less cost-effective than docetaxel-first sequencing for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

Patients' preferences for delaying metastatic castration-resistant prostate cancer: Combining health state and treatment valuation.

PURPOSE: Men with castration-resistant prostate cancer (CRPC) experience disease progression at different rates. The purpose of this study was to quantify the strength of patient preferences for delaying prostate cancer progression utilizing a discrete choice experiment (DCE) and valuing 3 health states in the continuum of CRPC. PATIENTS AND METHODS: Men with CRPC, recruited from US patient panels, completed a cross-sectional web-based survey. The survey consisted of vignette-based time trade-off and a DCE designed to quantify patients' willingness to pay to delay metastatic CRPC. Three health states were presented: (1) living with non-metastatic castration-resistant prostate cancer (nmCRPC) (2) living with metastatic CRPC (mCRPC) before chemotherapy, and (3) living with mCRPC either on or after chemotherapy. The DCE consisted of 15 hypothetical choices with attributes characterizing CRPC (pain, fatigue, out of pocket cost, dosing, and time until cancer metastasizes). Patients' willingness to pay for changes in each attribute were derived. RESULTS: A total of 176 patients with CRPC were surveyed (mean age: 64.2 years; 74% nmCRPC). Patients valued the nmCRPC health state (0.865) significantly higher than mCRPC before chemotherapy (0.743) or mCRPC on or after chemotherapy (0.476), both P < 0.001. In the DCE, patient treatment valuation was most affected by increasing the number of months until cancer metastasized; patients were willing to pay an additional $682 per month to delay time to metastases from 6 to 24 months (95% Confidence Interval: $387-$977) and additional $1,041 per month to delay time to metastasis to 48 months (95% Confidence Interval: $591-$1,490). CONCLUSIONS: The results of this study demonstrated men with CRPC place significant value on delaying metastases. This study represents the first time 2 stated preference methods, time trade-off and DCE, were used together to understand patients' preferences and valuation of health states in CRPC.

Cabazitaxel schedules in metastatic castration-resistant prostate cancer: a review.

Cabazitaxel (25 mg/m2 every 3 weeks) is the standard second-line chemotherapy for patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. It is associated with a risk of neutropenic complications, which may be a barrier to its use in daily clinical practice, particularly in frail elderly patients. Here the authors reviewed key studies conducted with cabazitaxel (TROPIC, PROSELICA, AFFINITY, CARD and the European compassionate use program) and pilot studies with adapted schedules. Based on this review, the use of prophylactic granulocyte colony-stimulating factor from cycle 1 appears crucial to maximize the benefit-risk ratio of cabazitaxel in metastatic castration-resistant prostate cancer. Preliminary data with alternative schedules look promising, especially for frail patients. Results of the ongoing Phase III CABASTY trial (ClinicalTrials.gov: NCT02961257) are awaited.

Cost-effectiveness analysis of cabazitaxel for metastatic castration resistant prostate cancer after docetaxel and androgen-signaling-targeted inhibitor resistance.

BACKGROUND: The aim of our study was to evaluate the cost-effectiveness of cabazitaxel versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel who had progression within 12 months while receiving an alternative inhibitor (abiraterone or enzalutamide) from a US payer's perspective. METHODS: To conduct the cost-effectiveness analysis, a Markov decision model was established. Three health states (progression-free survival (PFS), progressive disease (PD) and death) were included, and the incremental cost-effectiveness ratio (ICER) was regarded as the primary endpoint. The willingness-to-pay (WTP) threshold was set at $100,000.00/quality-adjusted life year (QALY), and discounted rates were set at 3% annually. Efficacy data were derived from the CARD trial and Weibull distribution curves were modeled to fit the survival curves. The robustness of the analysis was tested with a series of one-way sensitivity analyses and probabilistic sensitivity analyses. RESULTS: Overall, the incremental effectiveness and cost of cabazitaxel versus androgen-signaling-targeted inhibitors (ASTIs) were 0.16 QALYs and $49,487.03, respectively, which yielded an ICER of $309,293.94/QALY. Our model was mostly sensitive to the duration of PFS in the cabazitaxel group, cost of cabazitaxel and utility of the PFS state. At a WTP threshold of $100,000.00/QALY, cabazitaxel was the dominant strategy in 0% of the simulations. CONCLUSIONS: Cabazitaxel is unlikely to be a cost-effective treatment option compared with ASTIs in patients with mCRPC previously treated with docetaxel who had progression within 12 months while receiving ASTIs.

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.

Time spent in hormone-sensitive and castration-resistant disease states in men with advanced prostate cancer, and its health economic impact: registry-based study in Sweden.

OBJECTIVE: To investigate time spent in hormone-sensitive and castration-resistant disease states in men with advanced prostate cancer in Sweden, and the associated health economic impact. MATERIALS AND METHODS: Registry study (NCT03619980) of the Prostate Cancer data Base Sweden with data from the National Prostate Cancer Register, including the Patient-overview Prostate Cancer (PPC) and other national healthcare registries. The primary endpoint was time in each disease state. Secondary endpoints were co-medications, comorbidities and healthcare resource utilization (HRU) and cost in each disease state. RESULTS: In total, 1,869 men with advanced prostate cancer registered in PPC between 2014 and 2016, with data on the start of androgen deprivation therapy, were identified. Median time to progression and median survival were 4 and 11 years, respectively, for men with non-metastatic (nm) hormone-sensitive prostate cancer (HSPC); 1 and 7 years for men with metastatic (m) HSPC; and 1 and 8.5 years for men with nm castration-resistant prostate cancer (CRPC). Median survival for men with mCRPC was 4 years. Total annual mean costs for HRU per patient increased with increasing severity of disease, from 41,064 Swedish krona (SEK) for nmHSPC to 288,242 SEK for mCRPC. CONCLUSION: Progression time from mHSPC and nmCRPC to the mCRPC state was short and survival in the mCRPC state was approximately 4 years. Survival times were longer than expected, likely due to the selection of long-term survivors among prevalent cases. Healthcare costs were high for men with mCRPC. Further studies are needed to confirm our pilot study findings.

Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer.

In the absence of curative therapies, treatment of metastatic castrate-resistant prostate cancer (mCRPC) using currently available drugs can be improved by integrating evolutionary principles that govern proliferation of resistant subpopulations into current treatment protocols. Here we develop what is coined as an 'evolutionary stable therapy', within the context of the mathematical model that has been used to inform the first adaptive therapy clinical trial of mCRPC. The objective of this therapy is to maintain a stable polymorphic tumor heterogeneity of sensitive and resistant cells to therapy in order to prolong treatment efficacy and progression free survival. Optimal control analysis shows that an increasing dose titration protocol, a very common clinical dosing process, can achieve tumor stabilization for a wide range of potential initial tumor compositions and volumes. Furthermore, larger tumor volumes may counter intuitively be more likely to be stabilized if sensitive cells dominate the tumor composition at time of initial treatment, suggesting a delay of initial treatment could prove beneficial. While it remains uncertain if metastatic disease in humans has the properties that allow it to be truly stabilized, the benefits of a dose titration protocol warrant additional pre-clinical and clinical investigations.

Predictors of survival, healthcare resource utilization, and healthcare costs in veterans with non-metastatic castration-resistant prostate cancer.

OBJECTIVES: The objective of this study was to evaluate the association of prostate-specific antigen doubling time (PSADT) with metastasis-free survival (MFS) and overall survival (OS), and to describe healthcare resource utilization (HRU) and costs among patients with non-metastatic castrate-resistant prostate cancer (nmCRPC) in the Veterans Health Administration setting. METHODS AND MATERIALS: Patients with nmCRPC were identified from the Veterans Health Administration electronic health record database (1/2007-8/2017). PSADT was categorized as <3 months, 3 to 9 months, 9 to 15 months, ≥15 months, and unknown. MFS and OS were assessed using multivariable Cox proportional hazards regression, including PSADT as a predictor. HRU and costs were described per-patient-per-year (PPPY). RESULTS: Among 12,083 patients in the study, shorter PSADT was associated with shorter MFS and OS (PSADT <3 months vs. PSADT ≥15 months hazard ratio [HR] [95% confidence interval (CI)] = 0.307 [0.281, 0.335] and 0.371 [0.335, 0.410], respectively). Patients who developed metastasis had a 3-fold higher risk of death compared to those without metastasis (HR [95% CI] = 2.933 [2.763, 3.113]). Mean HRU increased following the onset of nmCRPC and metastatic castrate-resistant prostate cancer (mCRPC); mean inpatient stays more than doubled (0.2 vs. 0.5 and 0.6 vs. 2.8 PPPY, respectively). Similar increases in healthcare costs were observed; pharmacy costs more than tripled following nmCRPC ($2,074 vs. $6,839 PPPY). From nmCRPC to mCRPC, large increases were observed for inpatient costs ($7,257-$61,691), emergency room costs ($844-$1,958), and pharmacy costs ($4,115-$26,279) PPPY. CONCLUSIONS: In Veterans with nmCRPC, shorter PSADT was significantly associated with shorter MFS and OS. Onset of nmCRPC and mCRPC was associated with substantial HRU and cost increases.

Economic Outcomes in Patients with Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide or Abiraterone Acetate Plus Prednisone.

INTRODUCTION: Prostate cancer (PC) is the second leading cause of cancer death among US men and accounts for considerable healthcare expenditures. We evaluated economic outcomes in men with chemotherapy-naïve metastatic castration-resistant PC (mCRPC) treated with enzalutamide or abiraterone acetate plus prednisone (abiraterone). METHODS: We performed a retrospective analysis on 3174 men (18 years or older) utilizing the Veterans Health Administration (VHA) database from 1 April 2014 to 31 March 2018. Men with mCRPC were included if they had at least one pharmacy claim for enzalutamide or abiraterone (first claim date = index date) following surgical or medical castration, had no chemotherapy treatment within 12 months prior to the index date, and had continuous VHA enrollment for at least 12 months pre- and post-index date. Men were followed until death, disenrollment, or end of study and were 1:1 propensity score matched (PSM). All-cause and PC-related resource use and costs per patient per month (PPPM) in the 12 months post index were compared between matched cohorts. RESULTS: We identified 1229 men with mCRPC prescribed enzalutamide and 1945 prescribed abiraterone with mean ages of 74 and 73 years, respectively. After PSM, each cohort had 1160 patients. The enzalutamide cohort had fewer all-cause (2.51 vs 2.86; p < 0.0001) and PC-related outpatient visits (0.86 vs 1.03; p < 0.0001), with corresponding lower all-cause ($2588 vs $3115; p < 0.0001) and PC-related ($1356 vs $1775; p < 0.0001) PPPM outpatient costs compared with the abiraterone cohort. All-cause total costs (medical and pharmacy) PPPM ($8085 vs $9092; p = 0.0002) and PC-related total costs PPPM ($6321 vs $7280; p < 0.0001) were significantly lower in the enzalutamide cohort compared with the abiraterone cohort. CONCLUSIONS: Enzalutamide-treated men with chemotherapy-naïve mCRPC had significantly lower resource utilization and healthcare costs compared with abiraterone-treated men.

Prostate cancer (PC) is the second leading cause of death among men with cancer in the USA. Healthcare costs associated with PC, including hospitalizations, outpatient visits, and medications prescribed to treat adverse effects, depend on the severity of the disease and intensity of treatment, but are generally very high. Enzalutamide and abiraterone acetate with prednisone (abiraterone) are both approved treatments for men with PC that does not respond to treatments that reduce the male hormone testosterone, known as castration-resistant PC (CRPC). These drugs are associated with varying treatment duration and different adverse effects, and therefore could result in differences in the use of healthcare resources and overall cost of treatment. Here we evaluated the healthcare resource utilization (HCRU), which was calculated as the average number of healthcare encounters, including inpatient stays, outpatient visits, and pharmacy visits, and length of inpatient stays, and treatment costs associated with use of enzalutamide or abiraterone by men with metastatic CRPC (mCRPC), who had not received prior chemotherapy in the Veterans Health Administration. We found that men with chemotherapy-naïve mCRPC treated with enzalutamide used less healthcare resources and incurred lower total healthcare costs than men treated with abiraterone. On average, all-cause total healthcare costs were $1007 per patient per month lower and PC-related total healthcare costs were $959 per patient per month lower for patients treated with enzalutamide than those treated with abiraterone. These results support the hypothesis that the long-term HCRU and costs of enzalutamide may be lower compared with abiraterone.

Budget Impact of Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Prostate cancer is the most common cancer and second-leading cause of cancer death among men in the United States. Prostate cancer poses a large economic burden, which increases with progression from localized to metastatic disease. Newly approved treatments for non-metastatic castration-resistant prostate cancer (nmCRPC) delay disease progression and reduce the risk of metastatic disease. Quantifying the potential budget impact of these new treatments is of interest to health care decision makers. OBJECTIVE: To estimate the budget impact of enzalutamide for the treatment of patients with nmCRPC in the United States over a 3-year time horizon. METHODS: An Excel-based model was developed to estimate the budget impact to a U.S. health plan of enzalutamide, a second-generation antiandrogen, as an add-on to androgen deprivation therapy (ADT) for the treatment of high-risk nmCRPC patients (prostate-specific antigen doubling time of ≤ 10 months). Comparators include apalutamide + ADT, bicalutamide + ADT, and ADT only. The analysis includes treatment costs for nmCRPC and for treatment after progression to metastatic castration-resistant prostate cancer (mCRPC). The treated population size was estimated from epidemiological data and literature. Dosing, duration of therapy, and adverse event rates were based on package inserts and pivotal studies. RED BOOK, Centers for Medicare & Medicaid Services fee schedules, and literature were used to obtain costs of drugs, adverse events, and health care visits. Market shares were estimated for each comparator before and after enzalutamide adoption. A 1-way sensitivity analysis was performed to quantify the impact of parameter uncertainty. RESULTS: In a hypothetical 1-million-member plan with 3% annual growth, it was estimated that there would be approximately 19 eligible incident nmCRPC patients in year 1, increasing to 20 eligible incident patients in year 3. With an assumed market share of approximately 6% for enzalutamide in year 1, the budget impact would be $106,074 ($0.009 per member per month [PMPM]). With a 26% enzalutamide share in year 3, the budget impact would be $632,729 ($0.048 PMPM). Cumulative budget impact to the health plan over 3 years is estimated to be $1,082,095 ($0.028 PMPM). The increased cost of the treatment regimen is partly offset by reduced postprogression costs. CONCLUSIONS: Treatment of nmCRPC patients with enzalutamide has a modest budget impact that is partly offset by delaying progression to mCRPC. DISCLOSURES: This research was sponsored by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. All authors contributed to the development of the manuscript and maintained control over the final content. Schultz is employed by Astellas Pharma and owns stock in Gilead Sciences and Shire. O'Day and Sugarman are employees of Xcenda, which received consultancy fees from Astellas Pharma. Ramaswamy is employed by Pfizer. A synopsis of the current study was presented in poster format at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2019, in San Diego, CA, on March 25-28, 2019.

Utilization and Outcomes of Surgical Castration in Comparison to Medical Castration in Metastatic Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT) is the gold standard for metastatic prostate cancer, which can be achieved either by surgical or medical castration. In this study, we evaluated the trends of utilization of surgical castration and also assess the survival differences of patients who underwent surgical castration when compared with those who underwent medical castration. MATERIALS AND METHODS: The National Cancer Database was used to identify patients with metastatic prostate cancer from 2004 to 2014. Cochran-Armitage tests were used to assess temporal trends in the proportion of patients receiving surgical castration relative to medical castration. Logistic and Cox regression models were utilized to estimate the odds of utilization of surgical castration and the effect of castration on overall survival (OS). RESULTS: A total of 33,585 patients with metastatic prostate cancer were identified; 31,600 (94.1%) had medical castration, and 1985 (5.9%) underwent surgical castration. There was significant decline in the trend of utilization of surgical castration from 8.6% in 2004 to 3.1% in 2014. On multivariable analysis, being of a non-Caucasian race, having lower median income levels, having non-private insurance, and earlier years of diagnosis were found to be associated with increased odds of choosing surgical castration over medical castration. Notably, the odds of surgical castration were lower at academic centers. On univariable analysis, a survival difference between castration modality was evidenced (P < .01); 5-year OS for medical castration and surgical castration were 24.3% and 18.2%, respectively. However, on multivariable analysis, there was no OS difference between surgical castration and medical castration (P = .13). CONCLUSIONS: In this large contemporary analysis, the utilization of surgical castration has declined over time, with no OS difference when compared with medical castration. Increasing the utilization of surgical castration could help reduce health care expenditures. With rising health care costs, patients and physicians need to be aware of treatment options and their financial implications.

Cost-effectiveness analysis of metformin with enzalutamide in the metastatic castrate-resistant prostate cancer setting.

INTRODUCTION: Enzalutamide (Enza) is an effective treatment for metastatic castrate-resistant prostate cancer (mCPRC). However, Enza is not cost-effective (CE) at willingness to pay (WTP) thresholds from $0-$125 000/quality adjusted life years (QALYs) and is therefore a strain on valuable health care dollars. Metformin (Met) is inexpensive (~$8.00/month) and is thought to improve prostate cancer specific and overall survival compared to those not taking Met. We hypothesized that there must be an added effect Met could provide that would make Enza CE thereby alleviating this financial strain on government health care budgets. MATERIALS AND METHODS: We constructed a Markov model and performed a threshold analysis to narrow in on the added effect needed to make such a combination therapy cost-effective at various WTP thresholds. RESULTS: At a WTP threshold of $50 000/QALY Enza + Met is unlikely to be CE unless it increases Enza's efficacy by more than 30%. At a WTP threshold of $100 000, Enza + Met could be CE barring Met adds 18.73% to the efficacy of Enza. CONCLUSIONS: Enza + Met is unlikely to be CE at WTP thresholds less than $100 000/QALY; these results make sense because a therapy that is not CE at these WTP thresholds by itself is unlikely to be CE with an adjuvant therapy that keep a patient on such a treatment for even longer. Finally, our model suggests that the mCRPC setting is not the optimal place to trial adding Met as the relative costs are high and utility values low.

Health Care Resource Utilization and Costs Associated with Corticosteroid Use in Patients with Castration-Resistant Prostate Cancer: An Administrative Claims Analysis.

BACKGROUND: Corticosteroids are used in the management of castration-resistant prostate cancer (CRPC) to reduce tumor-related symptoms because of CRPC therapies. Since corticosteroids have been associated with a range of toxicities, their use may increase the economic burden sustained by patients with CRPC. However, the economic impact of using corticosteroids in patients with CRPC has not been well characterized. OBJECTIVE: To assess the effect of previous corticosteroid use on health care resource utilization (HRU) and health care costs among men with CRPC. METHODS: Using administrative claims data (2007-2016), adult chemotherapy-naive patients who initiated CRPC treatment following surgical or medical castration were identified. Based on the cumulative corticosteroid dose during the 12 months before CRPC treatment initiation, patients were grouped into 4 cohorts: no corticosteroid (0 gm), low corticosteroid (< 0.5 gm), medium corticosteroid (0.5-2.0 gm), and high corticosteroid (> 2.0 gm). All-cause HRU and costs (2017 U.S. dollars) were compared between cohorts during the 1-year study period following CRPC treatment initiation using the no corticosteroid cohort as reference. Multivariable regression models were used to adjust for baseline covariates, including age, region, index year, Charlson Comorbidity Index score, presence of bone metastases, baseline all-cause HRU, and corticosteroid-related clinical events during baseline. RESULTS: 9,425 patients were included (no corticosteroid = 6,765, low corticosteroid = 1,660, medium corticosteroid = 655, and high corticosteroid = 345). On average, patients in the no corticosteroid cohort were older and had a lower baseline HRU and comorbidity burden than patients in the other 3 cohorts. During the study period, patients with corticosteroid exposure (across all corticosteroid cohorts) had significantly more inpatient admissions (high corticosteroid vs. no corticosteroid adjusted incidence rate ratio [IRR] = 1.56; P < 0.001), emergency department visits (high corticosteroid vs. no corticosteroid adjusted IRR = 1.30; P = 0.001), and outpatient visits (high corticosteroid vs. no corticosteroid adjusted IRR = 1.11; P < 0.001). In addition, compared with the no corticosteroid cohort, patients with corticosteroid exposure had significantly higher monthly total costs (high corticosteroid vs. no corticosteroid adjusted difference = $2,600; P < 0.001), including medical service costs (high corticosteroid vs. no corticosteroid adjusted difference = $1,564; P < 0.001) and pharmacy costs (high corticosteroid vs. no corticosteroid adjusted difference = $825; P < 0.001). CONCLUSIONS: Cumulative corticosteroid exposure before CRPC treatment initiation was associated with significantly higher HRU and costs. This increase in economic burden was more prominent among patients with annual cumulative corticosteroid doses of more than 2.0 gm. These results suggest that previous corticosteroid use may result in a higher economic burden among patients with CRPC. DISCLOSURES: This study was funded by Astellas Pharma (Northbrook, IL) and Medivation, a Pfizer Company (San Francisco, CA), the codevelopers of enzalutamide. The study sponsor was involved in the study design, data interpretation, and review. All authors contributed to the development of the manuscript and maintained control over the final content. Schultz and Wilson are employed by Astellas Pharma. Schultz owns stock in Gilead Sciences and Shire. Song and Yang are employed by Analysis Group, which received consultancy fees from Astellas Pharma. Ramaswamy is employed by Pfizer, and Lowentritt is employed by Chesapeake Urology and has served as a speaker and consultant for Astellas Pharma, Pfizer, Bayer, Dendreon, and Janssen. A synopsis of the current research was presented in poster format at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2019, which took place in San Diego, CA, on March 25-28, 2019.

Evaluation of Treatment Patterns and Costs in Patients with Prostate Cancer and Bone Metastases.

BACKGROUND: There are a lack of guideline recommendations for patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment progression and sequencing. Understanding treatment patterns and associated utilization and costs may help inform stakeholders and guide decision making. OBJECTIVE: To describe treatment patterns and health care costs in prostate cancer (PC) patients with bone metastases treated with agents approved by the FDA for mCRPC. METHODS: 2 large integrated claims databases (MarketScan and PharMetrics) were used to identify males aged ≥ 18 years who were diagnosed and treated for PC (ICD-9-CM code 185.xx or 233.4) with bone metastases (ICD-9-CM code 198.5) from June 2013 to September 2014. Patients were required to be continuously enrolled for ≥ 6 months before and after initiation of treatment with abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, radium-223, sipuleucel-T, or other chemotherapy. Study endpoints included lines of therapy, health care resource utilization per patient per month (PPPM), PPPM costs, and mortality rate. Descriptive analysis was completed for the study sample, and survival function was calculated via Kaplan-Meier estimates. RESULTS: There were 953 patients meeting all inclusion criteria in the MarketScan database and 565 patients in the PharMetrics database. The median follow-up time was 18 months (interquartile range [IQR] = 14-23) for MarketScan and 14 months (IQR = 11-18) for PharMetrics. Mean age (SD) was 71 (± 10.7) and 66 (± 9.3) years, respectively. Before mCRPC treatment initiation, patients received palliative radiation therapy and bone antiresorptive therapy. For MarketScan and PharMetrics, respectively, 14.0% and 18.2% of patients received radiation therapy, 36.1% and 40.0% received denosumab; 16.5% and 16.8% received zoledronic acid; and 0.2% and 0.8% received pamidronate. Across both databases, abiraterone was the most commonly received bone metastasis treatment agent across all lines of therapy, except fourth line. Radium-223, cabazitaxel, and mitoxantrone were the least utilized therapies. The median cost PPPM during the post-index period was $10,916 (IQR=$5,334-$13,457) in MarketScan and $10,292 (IQR = $7,245-$14,699) in PharMetrics. The cost PPPM during the 6-month pre-index period was $2,643 (IQR = $850-$4,357) in MarketScan and $2,742 (IQR = $1,484-$4,730) in PharMetrics. CONCLUSIONS: Patients were treated mainly with abiraterone across most lines of care, with radium-223, cabazitaxel, and mitoxantrone as the least utilized therapies. Median costs PPPM increased by approximately $8,900 after initiation of FDA-approved agents for mCRPC, with the largest increase in cost stemming from oral medications. DISCLOSURES: Funding for this study was provided by Bayer HealthCare Pharmaceuticals. All authors were employees at Bayer HealthCare Pharmaceuticals at the time this study was conducted. This study was presented as a poster at the 2017 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.

Cost-effectiveness analyses and cost analyses in castration-resistant prostate cancer: A systematic review.

BACKGROUND: Treatment of metastatic prostate cancer is associated with high personal and economic burden. Recently, new treatment options for castration-resistant prostate cancer became available with promising survival advantages. However, cost-effectiveness of those new treatment options is sometimes ambiguous or given only under certain circumstances. The aim of this study was to systematically review studies on the cost-effectiveness of treatments and costs of castration-resistant prostate cancer (CRPC) and metastasizing castration-resistant prostate cancer (mCRPC) on their methodological quality and the risk of bias. METHODS: A systematic literature search was performed in the databases PubMed, CINAHL Complete, the Cochrane Library and Web of Science Core Collection for costs-effectiveness analyses, model-based economic evaluations, cost-of-illness analyses and budget impact analyses. Reported costs were inflated to 2015 US$ purchasing power parities. Quality assessment and risk of bias assessment was performed using the Consolidated Health Economic Evaluation Reporting Standards checklist and the Bias in Economic Evaluations checklist, respectively. RESULTS: In total, 38 articles were identified by the systematic literature search. The methodological quality of the included studies varied widely, and there was considerable risk of bias. The cost-effectiveness treatments for CRPC and mCRPC was assessed with incremental cost-effectiveness ratios ranging from dominance for mitoxantrone to $562,328 per quality-adjusted life year gained for sipuleucel-T compared with prednisone alone. Annual costs for the treatment of castration-resistant prostate cancer ranged from $3,067 to $77,725. CONCLUSION: The cost-effectiveness of treatments of CRPC strongly depended on the willingness to pay per quality-adjusted life year gained/life-year saved throughout all included costs-effectiveness analyses and model-based economic evaluations. High-quality cost-effectiveness analyses based on randomized controlled trials are needed in order to make informed decisions on the management of castration-resistant prostate cancer and the resulting financial impact on the healthcare system.

Treatment Duration, Healthcare Resource Utilization, and Costs Among Chemotherapy-Naïve Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide or Abiraterone Acetate: A Retrospective Claims Analysis.

INTRODUCTION: Enzalutamide and abiraterone acetate (plus prednisone) are new hormonal treatments for metastatic castration-resistant prostate cancer (mCRPC). This study compared treatment duration, healthcare resource utilization (HRU), and treatment costs for chemotherapy-naïve mCRPC patients treated with enzalutamide or abiraterone acetate in the USA. METHODS: Chemotherapy-naïve mCRPC patients initiating treatment with enzalutamide or abiraterone acetate were identified from administrative claims. Continuous enrollment ≥ 6 months before and ≥ 3 months after the index date (initiation date of enzalutamide or abiraterone acetate) was required. Treatment duration, all-cause and prostate cancer-related HRU, and costs were estimated during the post-index period. Multivariable analyses compared HRU and costs between cohorts, adjusting for baseline characteristics. RESULTS: Overall, 920 chemotherapy-naïve patients initiated enzalutamide and 2310 initiated abiraterone acetate (median follow-up, 10.7 and 13.5 months, respectively). More enzalutamide-treated patients had corticosteroid-sensitive comorbidities at baseline. Treatment duration was longer with enzalutamide versus abiraterone acetate (median, 10.7 vs. 8.8 months; P = 0.008). Enzalutamide was associated with fewer all-cause inpatient admissions [adjusted incidence rate ratio (95% confidence interval) 0.87 (0.76, 0.99)], days of hospitalization [0.84 (0.70, 1.02)], and outpatient visits [0.94 (0.90, 0.98)], and fewer prostate cancer-related outpatient visits [0.92 (0.87, 0.96)] compared with abiraterone acetate. Enzalutamide was also associated with lower prostate cancer-related inpatient and emergency department costs [adjusted differences, $122 (P = 0.024) and $28 (P = 0.009), respectively]. CONCLUSION: Chemotherapy-naïve mCRPC patients treated with enzalutamide versus abiraterone acetate had longer treatment duration and incurred lower HRU and prostate cancer-related inpatient and emergency department costs. FUNDING: Astellas Pharma Inc.

Burden of illness of chemotherapy in castration-resistant prostate cancer patients in Japan: a retrospective database analysis.

OBJECTIVE: The objective was to assess the burden of chemotherapy for castration-resistant prostate cancer (CRPC) in Japan. METHODS: Utilizing a large administrative hospital database we compared a set of outcome measures 12 months before and after initiation of chemotherapy, namely total medical costs, number of outpatient visits, number of hospital admissions and number of days spent in hospital. RESULTS: A total of 598 CRPC patients were identified in the database. Total healthcare costs increased from 143,578 Japanese Yen (JPY) per patient per month (PPPM), before chemotherapy, to 333,628 JPY after start of chemotherapy. The number of hospital admissions increased by 280%, and the number of days spent in hospital by 380%. CONCLUSIONS: The overall costs of chemotherapy for patients diagnosed with castration-resistant prostate cancer in Japan are high. Our findings can serve as a basis for health economic evaluations.

Treatments for Metastatic Prostate Cancer (mPC): A Review of Costing Evidence.

BACKGROUND: Prostate cancer (PC) is the most common cancer in Western countries. More than one third of PC patients develop metastatic disease, and the 5-year expected survival in distant disease is about 35%. During the last few years, new treatments have been launched for metastatic castrate-resistant prostate cancer (mCRPC). OBJECTIVES: We aimed to review the current literature on health economic analysis on the treatment of metastatic prostate cancer (mPC), compare the studies, summarize the findings and make the results available to administrators and decision makers. METHODS: A systematic literature search was done for economic evaluations (cost-minimization, cost-effectiveness, cost-utility, cost-of-illness, cost-of-drug, and cost-benefit analyses). We employed the PubMed® search engine and searched for publications published between 2012 and 2016. The terms used were "prostate cancer", "metastatic" and "cost". An initial screening of all headlines was performed, selected abstracts were analysed, and finally the full papers investigated. Study characteristics, treatment and comparator, country, type of evaluation, perspective, year of value, time horizon, efficacy data, discount rate, total costs and sensitivity analysis were analysed. The quality was assessed using the Quality of Health Economic Studies (QHES) instrument. RESULTS: A total of 227 publications were detected and screened, 58 selected for full-text assessment and 31 included in the final analyses. Despite the significant international literature on the treatment of mCRPC, there were only 15 studies focusing on cost-effectiveness analysis (CEA). Medical treatment constituted two thirds of the selected studies. Significant costs in the treatment of mCRPC were disclosed. In the pre-docetaxel setting, both abiraterone acetate (AA) and enzalutamide were concluded beyond accepted cost/quality-adjusted life year limits. In the docetaxel refractory setting, most studies concluded that enzalutamide was cost-effective and superior to AA. In most studies, cabazitaxel was not recommended, because of high cost. Looking at bone-targeting drugs, generic zoledronic acid (ZA) was recommended. External beam radiotherapy (EBRT) was analysed in three studies, and single fraction radiotherapy was concluded to be cost saving. Radium-223 was documented as beneficial, but costly. The quality of the studies was generally good, but sensitivity analyses, discounting and the measurement of health outcomes were present in less than two thirds of the selected studies. CONCLUSIONS: The treatment of mCRPC was associated with significant cost. In the post-docetaxel setting, single fraction radiotherapy and enzalutamide were considered cost-effective in most studies. Generic ZA was the recommended bone-targeting therapy.

Docetaxel chemotherapy in metastatic castration-resistant prostate cancer: cost of care in Medicare and commercial populations.

OBJECTIVE: To estimate the healthcare costs and characteristics of docetaxel chemotherapy episodes of care for men with metastatic castration-resistant prostate cancer (mCRPC). METHODS: This study used the Medicare 5% sample and MarketScan Commercial (2010-2013) claims data sets to identify men with mCRPC and initial episodes of docetaxel treatment. Docetaxel episodes included docetaxel claim costs from the first claim until 30 days after the last claim, with earlier termination for death, insurance disenrollment, or the end of a 24-month look-forward period from initial docetaxel index date. Docetaxel drug claim costs were adjusted for 2011 generic docetaxel introduction, while other costs were adjusted to 2015 values using the national average annual unit cost increase. RESULTS: This study identified 281 Medicare-insured and 155 commercially insured men, with 325 and 172 docetaxel episodes, respectively. The average number of cycles (unique docetaxel infusion days) per episode was 6.9 for Medicare and 6.3 for commercial cohorts. The average cost per episode was $28,792 for Medicare and $67,958 for commercial cohorts, with docetaxel drug costs contributing $2,588 and $13,169 per episode, respectively. The average cost per episode on docetaxel infusion days was $8,577 (30%) for Medicare and $28,412 (42%) for commercial. Non-docetaxel infusion day costs included $7,074 (25%) for infused or injected drugs for Medicare, $10,838 (16%) for commercial cohorts, and $6,875 (24%) and $9,324 (14%) for inpatient admissions, respectively. LIMITATIONS: The applicability is only to the metastatic castration-resistance clinical setting, rather than the metastatic hormone-sensitive setting, and the lack of data on the cost effectiveness of different sequencing strategies of a range of systemic therapies including enzalutamide, abiraterone, radium-223, and taxane chemotherapy. CONCLUSION: The majority of docetaxel episode costs in Medicare and commercial mCRPC populations were non-docetaxel drug costs. Future research should evaluate the total cost of care in mCPRC.