Skeletal-related Events Costs Research Articles

Patterns of care and economic consequences of using bone-targeted agents for castration-sensitive prostate cancer patients with bone metastases to prevent skeletal-related events in Switzerland - the SAKK 95/16 prostate study.

International guidelines state that bone-targeted agents such as denosumab or zoledronic acid at doses used for bone metastasis are not indicated for patients with metastatic castration-sensitive prostate cancer (mCSPC) with bone metastases. Whereas denosumab has never been studied in this patient population, zoledronic acid has been shown to be ineffective in decreasing the risk for skeletal-related events. This study estimates the prevalence and economic consequences of real-world use of bone-targeted agents for mCSPC patients in Switzerland. To estimate the frequency of bone-targeted agent administration and skeletal-related events, data from a non-interventional, cross-sectional survey involving oncologists across Switzerland (SAKK 95/16) was combined with data from the Swiss National Institute for Cancer Epidemiology and Registration (NICER). Economic parameters were calculated from the perspective of the healthcare system over the median time to prostate-specific antigen (PSA) progression for the extrapolated patient group, using data from NICER. The cost calculation covered costs for bone-targeted agents, their administration and skeletal-related events. The time to PSA progression (33.2 months), as well as the probability and cost of skeletal-related events were derived from the literature. The survey was answered by 86 physicians treating 417 patients, of whom 106 (25.4%) had prostate cancer, with 36 (34.0%) of these mCSPC. The majority of mCSPC patients (52.8%, n = 19) received bone-targeted agents monthly. Denosumab was the treatment of choice in 84.2% of patients (n = 16). Extrapolation using data from NICER indicated that 568 mCSPC patients may be treated with bone-targeted agents at doses used for bone metastasis  every year in Switzerland, leading to estimated total costs of more than CHF 8.3 million over 33.2 months. Because of its more frequent prescription and higher price, it appears that almost 93% of the total costs can be attributed to denosumab. For both denosumab and zoledronic acid, the most expensive components were the cost of administration and the drug cost, making up more than 90% of the total costs, with the rest being costs of skeletal-related events. This study found that the administration of bone-targeted agents in doses used for bone-metastatic diseases to prevent skeletal-related events is frequent in the setting of mCSPC and results in significant costs for the healthcare system.

The burden of skeletal-related events in four Latin American countries: Argentina, Brazil, Colombia, and Mexico

Aim Skeletal-related events (SREs) are major bone complications that frequently occur in patients with solid tumors (ST) and bone metastases, and in patients with multiple myeloma (MM). SREs include pathological fracture, spinal cord compression, radiation to bone, and surgery to bone. Limited data are available regarding the burden of SREs in Latin America. We built an economic model to quantify the current and future economic burden of SREs among adults in four Latin American countries: Argentina, Brazil, Colombia, and Mexico. Methods A comprehensive literature review with a systematic search strategy was conducted to parameterize the economic burden of illness (BOI) model. Economic analyses were conducted using a prevalence-based model. Aggregate SRE costs obtained from country-specific sources were used. We also included patient productivity losses. Costs were expressed in 2020 USD for the total annual burden, annual burden per 1,000 at risk, and projected five-year burden. Results The estimated total number of SREs was 251,503 in 2020, amounting to a total annual cost of USD 1.4 billion. The total projected five-year cost was USD 6.9 billion. Annual costs were highest in Brazil (USD 779.1 million), followed by Mexico (USD 281.8 million), Argentina (USD 174.6 million), and Colombia (USD 120.1 million). The average financial burden per 1,000 at risk was greatest in Brazil (USD 3.6 million), followed by Mexico (USD 3.4 million), Colombia (USD 2.9 million), and Argentina (USD 2.7 million). Conclusion Despite recommendations by medical societies for the use of bone-targeted agents in patients with solid tumors and bone metastasis or with multiple myeloma and bone lesions, a large proportion of patients at risk of experiencing SREs are not treated. Early detection of bone metastases and SREs and the use of the most effective preventative treatments are needed to decrease the clinical and economic burden of SREs in Latin America.

Trends of skeletal related events in patients with breast cancer metastasized to bone.

1098 Background: Up to three-quarters of women with advanced breast cancer develop bone metastases, predisposing to Skeletal Related Events (SRE), which are associated with a significant health care burden, poor prognosis, loss of functional independence and a decrease in quality of life. We performed a retrospective analysis on predictors of SRE in this population. We also evaluated temporal trends of outcomes and resource utilization in those with SRE. Methods: Adult breast cancer patients with metastases to bone, admitted from January 2012 to September 2015 were identified from the Nationwide Inpatient Sample database. Based on previous studies, SRE was defined by using ICD-9 codes for pathologic fracture, spinal cord compression, necessity for radiation to bone or surgery to bone. Multivariable analysis of predictors of SRE in patients with breast cancer metastatic to bone, as well as mortality in the SRE group were performed. Temporal trends of resource utilization across the years were evaluated. Results: A total of 143,455 patients with breast cancer with metastases to bone were identified, of which 17.2% had SRE. Patients with SRE had a mean age of 66 years and were predominantly white (70.2%). After adjusting for confounders, African Americans and Hispanics were less likely than Whites to develop SRE. On multivariable analysis, only comorbidity burden (in the form of high Charlson comorbidity index) predicted inpatient mortality. Rates of SRE in breast cancer patients with bone metastases did not change over the years (17.2% to 17.1%). Inpatient mortality of patients with SRE remained stable (3.76% to 3.79%). There was a statistically significant increase in surgical intervention (43.4% to 47.7%, p<0.01) and decrease in radiation to bone (25.7% to 19.7%, p<0.001) over time. Length of hospital stay and total hospital charges, after adjusting for inflation, remained largely unchanged. Conclusions: Incidence of SRE, inpatient outcomes and health care costs remained stagnant in those with metastatic breast cancer between 2012 and 2015, despite the advent of novel bone-targeted agents. There has been an increased trend towards surgical intervention and less utilization of local radiation over time. [Table: see text]

Examination of burden of skeletal-related events in patients naive to denosumab and intravenous bisphosphonate therapy in bone metastases from solid tumors population

Objectives: Skeletal-related events (SREs), i.e. pathologic fractures, spinal cord compression, surgery and radiation to bone, are serious skeletal complications that occur frequently in patients with bone metastases (BMs) from solid tumors (STs). Clinical guidelines recommend treatment with denosumab and intravenous bisphosphonates (IVBPs) to prevent SREs. However, therapy may be delayed by physicians due to perceived low risk of SREs or for other clinical reasons. This study estimated SRE incidence rates in treatment-naive (i.e. no denosumab or IVBPs) patients with BMs from STs in the US.Methods: In this retrospective cohort study adult patients with diagnoses of BM and ST between 1 January 2008 and 31 March 2015 were identified from MarketScan Databases. All patients had ≥6 months of data before the first BM diagnosis date (index date) and were followed for ≥6 months from the index date until the earliest of inpatient death, initiation of denosumab/IVBP therapy or end of data. The Kaplan–Meier curve was used to estimate cumulative incidence of SREs. The incremental healthcare cost of SREs was estimated and compared to propensity score matched non-SRE patients.Results: A total of 47,052 patients met the study criteria. Using the Kaplan–Meier method the cumulative incidences of SREs among treatment-naïve patients were 39.9% (95% confidence internal [CI]: 39.4–40.4), 46.3% (95% CI: 45.8–46.8), 52.5% (95% CI: 51.9–53.2) and 59.4% (95% CI: 58.6–60.3) by month 6, 12, 24 and 48 post index date, respectively. The SRE group was associated with higher all-cause total healthcare cost per-patient-per-year compared to those without SREs ($168,277 vs. $101,020, p < .001).Conclusions: Almost half (46.3%) of the treatment-naïve population with BMs from STs experience SREs within 1 year of the first BM diagnosis. SREs were associated with an average $67,257 additional healthcare cost annually. Given the high SRE burden in these patients, early initiation of prophylactic therapy should be considered.

Costs of skeletal-related events (SREs) in patients with metastatic castrate-resistant prostate cancer (mCRPC) treated with oral therapies.

e16539 Background: SREs are associated with increased mortality and costs for mCRPC patients. The impact of mCRPC oral therapies on SREs is not well understood in the real world. This study examined the occurrence of and health care costs associated with SREs among mCRPC patients treated with abiraterone acetate + prednisone (ABI) or enzalutamide (ENZ). Methods: A retrospective study of a large national health claims database identified patients initiated on ABI or ENZ from 9/2012- 6/2015. Patients included had: ≥1 claim with prostate cancer diagnosis (ICD-9-CM 185.x) from 6 mo. pre- to 30 days post-index; ≥6 mo. pre- + ≥3 mo. post-index health plan enrollment. Index was date initiated on first oral therapy (ABI/ENZ). SREs (spinal cord compression, radiation to bone, pathological fracture, bone surgery) were assessed and health care cost calculated for patients with/without SREs in baseline/follow-up. Descriptive analyses and Cox proportional hazards examined SREs; generalized linear models assessed costs. Models adjusted for ABI/ENZ, age, region, baseline comorbidities, bone/brain/visceral metastases, docetaxel, and statin use. Results: The table below summarizes unadjusted results. Total all-cause per patient per month (PPPM) costs of 1,516 patients were highest for those with follow-up SREs. A significant difference in cost exists when comparing across all groups. Among patients without baseline SREs, adjusted analysis found greater hazards of follow-up SREs for baseline bone metastases (HR: 1.62, P = 0.003), baseline visceral metastases (HR: 1.68, P &lt; 0.001), prior docetaxel (HR: 1.46, P = 0.004), and ENZ (vs. ABI) as first treatment (HR: 1.35, P = 0.013). Patients with follow-up SREs (with/without baseline SREs) had 19% higher adjusted costs compared to those without baseline or follow-up SREs (P &lt; 0.001 each). Conclusions: SREs were common among mCRPC patients and associated with a significant financial burden. [Table: see text]

Cost-effectiveness Analysis of Denosumab in the Prevention of Skeletal-related Events in Patients with Prostate Cancer in Kazakhstan.

IntroductionBone mass loss (BML) is one of the adverse effects of oncological chemotherapy, especially in cases of hormonal types of cancer, such as a prostate cancer (PC). BML is strongly associated with skeletal-related events (SREs), therefore decreasing the quality of patient’s life. Denosumab shows an advantage over zoledronic acid (ZA) in delaying the first onset of SREs and subsequent SREs in adults with PC in several phase III clinical trials. Since generic ZA recently became available, the purpose of the present study was to assess the cost-effectiveness of denosumab vs. brand or generic ZA in the prevention of SREs in Kazakhstani patients with PC.MethodsA Markov model was constructed in Tree-Age Pro 2013 software program with 4-week model cycles to analyze the cost-effectiveness of the treatments from the perspective of Ministry of Health (MoH) over a 10-year PC cohort. Direct costs (in Kazakhstani monetary units “tenge” in 2014) included costs of drug, SRE (pathologic fracture, surgery to bone, radiation to bone, spinal cord compression), and adverse events treatment. All costs were discounted for 3% per year. Effectiveness was appraised based on the number of SREs. Health states were defined according to SRE occurrence, SRE history, and death. The model assumed that a maximum of 1 SRE could occur in each cycle. Transition probabilities were derived from the relevant phase III trials. Results were present in the incremental total cost per SRE avoided. One-way sensitivity analyses were performed to examine the robustness of the model.ResultsOver the 10-year period, denosumab incurred 103,091 tenge higher costs than brand ZA, 677,133 tenge higher costs than generic ZA, and 0.58 fewer SREs per patient with PC. The estimated incremental total direct costs per SRE avoided with the use of denosumab were 177,743 tenge (instead of brand ZA) and 1,167,470 tenge (instead of generic ZA). Results were robust to one-way sensitivity analyses.ConclusionsWith the assumption that brand and generic ZAs are equally effective in the prevention of SREs in PC patients, denosumab seems to be a cost-effective alternative for brand ZA (insignificant difference in costs – less than 5%) and a costly alternative for generic ZA from the perspective of MoH of Kazakhstan.

Cost-Effectiveness of Denosumab vs. Brand or Generic zoledronic Acid in Patients with Breast Cancer in Kazakhstan.

Denosumab is recomended for preventing skeletal-related events (SREs) in adults with bone metastases from breast cancer (BC). Since recently generic zoledronic acid (ZA) became available, the aim of present study was to access the cost-effectiveness of denosumab vs. brand or generic ZA in the prevention of SREs in Kazakhstani patients with BC. An excel-based Markov model was constructed with 4-week model cycles to analyse the cost-effectiveness of the treatments from the perspective of Ministry of Health with a 10-year time horison for BC cohort. Direct costs (in 2014 tenge) included costs of drug, adverse event and SRE(pathologic fracture, surgery to bone, radiation to bone, spinal cord compression) treatment. A discount rate of 3% per year was applied for all costs. Effectiveness was appraised based on the number of SREs. The health states were defined according to SRE occurance,SRE history and death. The model assumed that a maximum of 1 SRE could occur in each cycle. Transition probabilities were derived from the relevant phase III trials. Results were present in the incremental total cost per SRE avoided. One-way sensitivity analyses were performed to examine the robustness of the model. Over 10-year period, denosumab incurred 1044 tenge lower costs than brand ZA, 568558 tenge higher costs than generic ZA, 1.28 fewer SREs per BC patient. The estimated incremental total direct costs per SRE avoided with the use of denosumab were -816 tenge (instead of brand ZA) and 444186 tenge (instead of generic ZA). Results were robust to one-way sensitivity analyses. With assumption that brand and generic ZAs are equally effective in the prevention of SREs in BC patients, denosumab seems to be cost-effective alternative for brand ZA, and costly alternative for generic ZA from a perspective of Ministry of Health of Republic of Kazakhstan.

Clinical and economic burden of bone metastasis and skeletal-related events in prostate cancer

We review the clinical trials and observational studies literature regarding the clinical and economic burden of bone metastasis and skeletal-related events (SREs) in prostate cancer, and discuss current gaps in understanding the impact of bone metastasis in this disease. Trial data indicate that SREs occur in half of prostate cancer patients with bone metastasis in the absence of treatment, and 30-45% among those who receive bone-modifying agents. In the United States, the cost of SRE ranged from $7553 per radiation episode to $88 838 per bone surgery episode. Prevalence of SRE, time to SRE occurrence, and cost of SRE varied across studies because of differences in study populations, follow-up period, and the algorithm used to measure SRE. There is limited evidence on the clinical and economic impact by SRE subtype. Information regarding patient-reported outcomes and costs from the patient's perspective is lacking. Bone metastasis and SREs in prostate cancer patients are associated with considerable morbidity, reduced survival, and substantial economic burden. Consistent study methodology, particularly the measurement of SREs, is necessary to allow comparison of estimates across studies. The inclusion of patient-centered clinical and economic outcomes in future research will provide pertinent information regarding the burden of bone metastasis and SREs.

Healthcare costs associated with skeletal-related events in breast cancer patients with bone metastases

Background:Patients with bone metastases secondary to breast cancer are pre-disposed to skeletal-related events (SREs), including spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (SB), and radiotherapy to bone (RT).Objective:To document current patterns of healthcare utilization and costs of SREs in patients with breast cancer and bone metastases.Methods:This was a retrospective, observational study using the Thomson MedStat MarketScan Commercial Claims and Encounters database from 9/2002 to 6/2011. Study subjects included all persons with claims for breast cancer and for bone metastases, and ≥1 claims for an SRE. Unique SRE episodes were identified based on a gap of at least 90 days without an SRE claim, and classified by treatment setting (inpatient or outpatient) and SRE type (SCC, PF, SB, or RT).Results:Of 17,266 patients with breast cancer and bone metastases, 9142 (53%) had one or more SRE episodes. Among 5809 patients who met all other criteria, there were 7617 SRE episodes over mean (SD) follow-up of 17.2 (15.2) months. The percentage of episodes that required inpatient treatment ranged from 11% (RT) to 76% (SB). On average, inpatient SCC episodes (n = 83 episodes) were most costly; while outpatient PF episodes (n = 552 episodes) were least costly. Of the total SRE costs (mean [SE] $21,072 [$36,462]/episode), 36% were attributable to outpatient RT (n = 5265 episodes) and 31% to inpatient PF (n = 838 episodes).Limitations:The administrative claims data used in this study may lack sensitivity and specificity for identification of clinical events and may not be generalizable to other populations. Also, for some SRE episode categories, the number of events was small and cost estimates may lack precision.Conclusion:In patients with breast cancer and bone metastases, SREs are associated with high costs and hospitalizations.

The Economic Burden of Skeletal-Related Events Among Elderly Men with Metastatic Prostate Cancer

Advanced prostate cancer patients with bone metastasis are predisposed to skeletal complications termed skeletal-related events (SREs). There is limited information available on Medicare costs associated with treating SREs. The objective of this study was to ascertain SRE-related costs among older men with metastatic prostate cancer in the US. We analysed patients aged 66years or older who were diagnosed with incident stage IV (M1) prostate cancer between 2000 and 2007 from the linked Surveillance, Epidemiology and End Results (SEER)-Medicare dataset. A propensity score for the incidence of an SRE was estimated using a logistic regression model including demographic and clinical baseline variables. Patients with SREs (cases) were matched to patients without SREs (controls) based on the propensity score, length of follow-up (i.e. date of prostate cancer diagnosis to last date of observation) and death. Health resource utilization cost differences between cases and controls over time were compared using generalized linear models. Healthcare costs were examined by type of SRE (pathological fracture only, pathological fracture with concurrent surgery, spinal cord compression only, spinal cord compression with concurrent surgery, and bone surgery only) and by source of care (inpatient, physician/non-institutional provider, skilled nursing facility, outpatient and hospice). All costs were adjusted to 2009 US dollars, using the medical care component of the Consumer Price Index. Application of the inclusion criteria resulted in 1,131 metastatic prostate cancer patients with SREs and 6,067 patients without SREs during follow-up. The average age of the sample was 79years, and 14% were African American. A total of 928 patients with SREs were matched to 928 patients without SREs. The average health care utilization cost of patients with SREs was US$29,696 (95% confidence interval [CI] US$24,730-US$34,662) higher than that of the controls. The most expensive SRE group was spinal cord compression with concurrent surgery (US$82,868: 95% CI US$67,472-US$98,264) followed by bone surgery only (US$37,496: 95% CI US$29,684-US$45,308), pathological fracture with concurrent surgery (US$34,169: 95% CI US$25,837-US$ 42,501), spinal cord compression only (US$25,793: 95% CI US$20,933-US$30,653) and pathological fracture only (US$14,649: 95% CI US$6,537-US$22,761). The largest cost difference by source of care was observed for hospitalizations (p<0.01). Metastatic prostate cancer patients with SREs incur higher costs compared to similar patients without SREs. SRE costs among older stage IV (M1) prostate cancer patients vary by SRE type, with spinal cord compression and concurrent surgery costing at least twice as much as other SREs.

Frequency, Health Care Resource Use (HCRU), and Costs Associated With Skeletal Related Events (SREs) In US Patients With Multiple Myeloma (MM)

BackgroundExisting data demonstrate that SREs can impose a significant economic burden. Much of the cost data for MM patients are combined with other tumor types and do not make comparisons between MM patients with SRE and MM patients without SRE. This research provides updated, comprehensive cost data in MM patients to address these gaps. MethodsPatients 18 years of age or older were required to have ≥2 claims in any position with a diagnosis of MM (ICD-9-CM codes 203.00, 203.01, 203.02), at least 30 days apart, between 01 January 2005 and 31 December 2010; the date of the first MM diagnosis was the index date. Marketscan(r) data were used to select patients continuously enrolled in a non-capitated commercial health plan with a medical and pharmacy benefit for 12 months before the index date (i.e., baseline period) and at least 3 months after the index date (post-index period). Patients were followed until the earliest of death or disenrollment from the health plan or end of the study period on 31 December 2011. MM patients with ≥ 1 SRE were compared to those without SRE to characterize the associated incremental cost of SRE. Frequency of SREs, HCRU (events/person-mth), and costs (USD/person-mth) were determined. Cost is defined as total gross payment to providers for a specific service, which includes amount paid by the patient and payer. Due to skewed distributions, bootstrapping (replication=1000) methodology was used to estimate standard error of rates of HCRU and costs and to compare cohorts. P-values were generated utilizing 2-sample t-tests. ResultsMM patients with SRE (n=596, mean age=67.8, 45.6 % male, mean Charlson/Deyo [CD] =1.1) were compared to MM patients without SRE (n=432, mean age=65.7, 47.5 % male, mean CD=0.8). Patients are categorized by number of SREs experienced during the study period in Table 1. MM patients with SRE experienced significantly greater HCRU during both the baseline and post-index periods (Tables 2&3). The HCRU increases translated into mean total costs for patients with SRE that were significantly greater during both the baseline (w/o SRE: USD 953; w/SRE: USD 1328; p=0.005) and post-index (w/o SRE: USD 3307; w/SRE: USD 4763; p<0.0001) periods. Increasing frequency of SRE was significantly associated with increasing trend of HCRU and cost throughout the study (all p values <0.0001). [Display omitted] [Display omitted] [Display omitted] ConclusionIn addition to the clinical burden, SREs significantly add to the economic burden associated with MM in US patients by increasing the rate of HCRU and cost. Disclosures:Smyth:Eli Lilly and Company: Employment, Equity Ownership. Off Label Use: The frequency of bisphosphonate use (both oral and IV) will be described in the poster. Conti:Eli Lilly and Company: Employment, Equity Ownership. Wooldridge:Eli Lilly and Company: Employment, Equity Ownership. Bowman:Eli Lilly and Company: Employment, Equity Ownership. Li:Eli Lilly and Company: Employment, Equity Ownership. Nelson:Eli Lilly and Company: Employment. Xie:Eli Lilly and Company: Employment, Equity Ownership. Ball:Eli Lilly and Company: Employment, Equity Ownership.

Cost of skeletal-related events in European patients with solid tumours and bone metastases: data from a prospective multinational observational study

Objectives:Patients with bone metastases often experience skeletal-related events (SREs: radiation or surgery to bone, pathologic fracture, and spinal cord compression). This study examined health resource utilization and costs associated with SREs.Methods:Data presented are from the European cohort (Germany, Italy, Spain, and the UK) of patients with solid tumours enrolled in a multi-national, prospective, observational study in patients with solid tumours or multiple myeloma. Patients with Eastern Cooperative Oncology Group score 0–2 and life expectancy ≥6 months, who experienced an SRE up to 97 days before enrolment, were eligible. Health resource utilization associated with SREs (including number/length of inpatient stays, numbers of procedures and outpatient visits) were collected through chart review for up to 97 days before enrolment and prospectively during follow-up. Country-specific cost calculations were performed.Results:In total, 478 eligible patients contributed 893 SREs to this analysis. Radiation to bone occurred most frequently (66% of total). Spinal cord compression (7%) and surgery to bone (10%) were the least common events, but most likely to require inpatient stays. The most costly SREs were also spinal cord compression (mean per SRE across countries, €4884–€12,082) and surgery to bone (€3348–€9407). Inpatient stays were the main cost drivers.Limitations:Health resource utilization used to calculate the costs associated with SREs may have been under-estimated as a result of exclusion of patients with low performance status or life expectancy; unavailable information and exclusion of resource consumption associated with pain. Thus, the estimate of associated costs is likely to be conservative.Conclusions:SREs result in considerable health resource utilization, imposing a substantial financial burden driven by inpatient stays. Treatments that prevent/delay SREs may help ease this burden, thereby providing cost savings across European healthcare systems.

Cost per patient and potential budget implications of denosumab compared with zoledronic acid in adults with bone metastases from solid tumours who are at risk of skeletal-related events: an analysis for Austria, Sweden and Switzerland

ObjectivesTo assess cost implications per patient, per year, and to predict the potential annual budget impact when patients with bone metastases secondary to solid tumours at risk of skeletal-related events...

Healthcare utilization and costs associated with skeletal-related events in prostate cancer patients with bone metastases

Patients with bone metastases secondary to prostate cancer are predisposed to skeletal-related events (SREs), including spinal cord compression, pathological fracture, surgery to bone and radiotherapy to bone. The objective of this study was to document current patterns of healthcare utilization and costs of SREs in patients with prostate cancer and bone metastases. This was a retrospective, observational study using the Thomson MedStat MarketScan Commercial Claims and Encounters database from September 2002 to June 2011. Study subjects included all persons with claims for prostate cancer and for bone metastases, and one or more claims for an SRE. Unique SRE episodes were identified based on a gap of at least 90 days without an SRE claim, and classified by treatment setting (inpatient or outpatient) and SRE type (spinal cord compression, pathological fracture, surgery to bone or radiotherapy). Of 3919 patients with prostate cancer and bone metastases, 2090 (53%) had one or more SRE episodes. Among 1237 patients who met all other criteria, there were 1623 SRE episodes over a mean (s.d.) follow-up of 16.1 (12.9) months. The percent of episodes that required inpatient treatment ranged from 14% (radiotherapy) to 82% (surgery to bone). On average, inpatient episodes with surgery to bone (n = 36 episodes) were most costly (mean (s.e.) $88,838 ($11,830)/episode), whereas outpatient episodes with surgery to bone (n = 8 episodes) were least costly (mean (s.e.) $4749 ($1690)/episode). Of the total SRE costs (mean (s.e.) $20,984 ($951)/episode), 41% were attributable to outpatient radiotherapy (n = 1169 episodes), 23% to inpatient radiotherapy (n = 184 episodes), and 19% to inpatient treatment of pathological fractures (n = 101 episodes). In patients with prostate cancer and bone metastases, SREs are associated with high costs and hospitalizations.

Health care utilization and costs associated with skeletal-related events (SREs) in patients with breast cancer (BC) and bone metastases (BMets).

72 Background: Patients with BMets secondary to BC are predisposed to SREs, defined as spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (SB), and radiation therapy to bone (RT). Information on health care utilization and costs to treat SRE episodes in BC patients are limited. The objective of this study was to document current patterns of healthcare utilization and costs of SRE in patients with BC and BMets. Methods: This was a retrospective, observational study using the Thomson MedStat MarketScan Commercial Claims and Encounters database from 9/2002 to 6/2011. Study subjects included all persons with claims for BC (ICD-9-CM 174.xx) and for BMets (ICD-9-CM 170.xx or 198.5x), and ≥1 claim(s) for SRE. Key inclusion criteria included no other primary cancer and continuous enrollment ≥6 mos prior to BMets diagnosis. Unique SRE episodes were identified based on a gap of ≥90 days without an SRE claim, and classified by treatment setting (inpatient [IP, hospitalized for SRE during episode] or outpatient [OP]) and SRE type (SCC; PF [and no SCC]; SB [and no SCC or PF]; RT [and no SCC, PF, or SB]). Results: Of 22,709 BC patients with BMets, 11,941 had ≥1 SRE. Among 5,809 patients who met all other criteria, there were 7,617 SRE episodes over a mean (SD) follow-up of 17.2 (15.2) mos. The percent of SRE episodes that required IP treatment ranged from 11% (RT) - 76% (SB) (23% overall). On average, IP SCC episodes were most costly; while OP PF episodes were least costly. Of the total SRE costs (mean [SD] $21,072 [$36,462]/episode), 36% were for OP RT and 31% were for IP PF. Conclusions: In patients with BC and BMets, SREs are frequent and associated with high costs and hospitalizations. OP RT and IP PF account for a large share of SRE costs. Treatments that prevent SREs in these patients may reduce these costs. [Table: see text]

Lifetime cost-effectiveness of denosumab versus zoledronic for prevention of skeletal-related events (SREs) in patients (pts) with castrate-resistant prostate cancer (CRPC) and bone metastases (BM): United States managed care perspective.

e15172 Background: Denosumab (Dmab) is superior to zoledronic acid (ZA) for prevention of SREs in pts with CRPC and BM. As Dmab is not cleared renally, it can be used in pts regardless of renal status or concomitant use of nephrotoxic drugs. Previous economic analyses were limited as the analyses were based on short duration-trial based perspectives and/or did not account for disutility associated with IV vs SC administration of ZA and Dmab, respectively. These analyses assess the lifetime cost-effectiveness of Dmab vs ZA in pts with CRPC and BM from a US managed care perspective, with extensive scenario and sensitivity analyses. Methods: A lifetime Markov model was developed, with efficacy of Dmab vs ZA in SRE prevention from a head-to-head phase 3 trial; clinical practice SRE rate in ZA pts from a large commercial claims database analysis; SRE and mode of administration (IV vs SC) quality adjusted life-year (QALY) decrements estimated using the time trade-off method; and SRE costs estimated from a nationally representative commercial claims database. Drug, drug administration, and renal monitoring costs were also included. Costs and QALYs were discounted at 3% per year. Scenario analyses (including adverse events, drug discontinuation, etc), one-way and multivariate probabilistic sensitivity analyses were conducted. Results: Dmab reduced the number of SREs and increased pts’ QALY vs ZA. In the base case and the scenario analyses, cost per QALY gained was below $50,000, which is commonly considered good value. Cost per SRE avoided was below $9,000. In one-way sensitivity analyses, drug costs and SRE rate were the most influential variables. Probabilistic sensitivity analyses showed the probabilities of Dmab being cost-effective vs ZA were 0.83, 0.94, and 0.98 with willingness-to-pay of $100,000, $150,000 and $200,000 per QALY gained, respectively. Conclusions: Dmab is a cost-effective treatment option in preventing SREs in pts with CRPC and BM compared with ZA from a US managed care perspective. The overall value of Denosumab is based on superior efficacy and more efficient administration.

Cost-Effectiveness of Denosumab Versus Zoledronic Acid in the Management of Skeletal Metastases Secondary to Breast Cancer

BackgroundDenosumab has been approved in the United States for the prevention of skeletal-related events (SREs) in metastatic breast cancer. In a Phase III trial in patients with bone-metastatic breast cancer (N = 2033), denosumab was associated with a significantly delayed time to first SRE (by 18%; P < 0.001 noninferiority; P = 0.01 superiority) and time to first and subsequent SREs (by 23%; P = 0.001). Overall survival (HR = 0.95; 95% CI, 0.81–1.11; P = 0.49) and disease progression (HR = 1.00; 95% CI, 0.89–1.11; P = 0.93) did not differ significantly between groups. Denosumab was associated with a nonsignificant reduction in serious adverse events (44.4% vs 46.5%). ObjectivesGiven the current ambiguity regarding the cost-effectiveness of these agents in light of these trial outcomes, the present analysis assessed, from a US payer perspective, the cost-effectiveness of denosumab versus zoledronic acid in patients with bone metastases secondary to breast cancer. MethodsA literature-based Markov model was developed to estimate the survival, quality-adjusted life-years (QALYs) gained, number and costs of SREs, and drug and administration costs in patients receiving denosumab or zoledronic acid over 27 and 60 months. Clinical inputs reproduced the trial outcomes. SRE-related costs and utilities were literature based. Costs and QALYs were discounted 3% annually. ResultsIn the 27-month base-case analysis, denosumab was associated with fewer SREs (−0.298), more QALYs (+0.0102), and lower SRE-related costs (−$2016), but higher drug-related (+$9123) and total costs (+$7107) versus zoledronic acid. The cost per QALY gained (ie, incremental cost-effectiveness ratio [ICER]) was $697,499. In sensitivity analyses, the ICER ranged from $192,472 to $1,340,901/QALY, depending on assumptions regarding treatment benefits, drug costs, and analytical horizon. In the probabilistic sensitivity analysis, denosumab was cost-effective in 2 of 5000 modeled replicates (0.04%). ConclusionsDespite the limitations of restricted availability of clinical data and uncertainty regarding the price of generic zoledronic acid, the findings from the present analysis suggest that the use of denosumab is associated with a high ICER compared with zoledronic acid. This finding may raise important questions regarding the economic value of denosumab in bone-metastatic breast cancer.

Cost-effectiveness of denosumab vs zoledronic acid for prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States

Objective:With increasing healthcare resource constraints, it has become important to understand the incremental cost-effectiveness of new medicines. Subcutaneous denosumab is superior to intravenous zoledronic acid (ZA) for the prevention of skeletal-related events (SREs) in patients with advanced solid tumors and bone metastases. This study sought to determine the lifetime cost-effectiveness of denosumab vs ZA in this setting, from a US managed-care perspective.Methods:A lifetime Markov model was developed, with relative rate reductions in SREs for denosumab vs ZA derived from three pivotal Phase 3 trials involving patients with castration-resistant prostate cancer (CRPC), breast cancer, and non-small-cell lung cancer (NSCLC), and bone metastases. The real-world SRE rates in ZA-treated patients were derived from a large commercial database. SRE and treatment administration quality-adjusted life year (QALY) decrements were estimated with time-trade-off studies. SRE costs were estimated from a nationally representative commercial claims database. Drug, drug administration, and renal monitoring costs were included. Costs and QALYs were discounted at 3% annually. One-way and probabilistic sensitivity analyses were conducted.Results:Across tumor types, denosumab was associated with a reduced number of SREs, increased QALYs, and increased lifetime total costs vs ZA. The costs per QALY gained for denosumab vs ZA in CRPC, breast cancer, and NSCLC were $49,405, $78,915, and $67,931, respectively, commonly considered good value in the US. Costs per SRE avoided were $8567, $13,557, and $10,513, respectively. Results were sensitive to drug costs and SRE rates.Limitations:Differences in pain severity and analgesic use favoring denosumab over ZA were not captured. Mortality was extrapolated from fitted generalized gamma function beyond the trial duration.Conclusion:Denosumab is a cost-effective treatment option for the prevention of SREs in patients with advanced solid tumors and bone metastases compared to ZA. The overall value of denosumab is based on superior efficacy, favorable safety, and more efficient administration.

Cost-effectiveness of denosumab (Dmab) versus zoledronic acid (ZA) for prevention of skeletal-related events (SREs) in patients (pts) with castrate-resistant prostate cancer (CRPC) and bone metastases (BM).

59 Background: It has become more important to understand the incremental cost/benefit of new medicines as healthcare costs rise. Subcutaneous Dmab is superior to intravenous ZA for prevention of SREs in pts with CRPC and BM (Fizazi, 2011). In addition, a lower proportion of pts receiving Dmab progressed to moderate/severe pain than those receiving ZA (Brown, 2011). Dmab can be used in pts regardless of renal status or concomitant use of nephrotoxic drugs. These analyses assess the lifetime, real world cost-effectiveness of Dmab vs ZA in pts with CRPC and BM from a US managed care perspective. Methods: A lifetime Markov model was developed to estimate SREs, quality adjusted life-years (QALYs), and costs. The relative rate reduction in SREs for Dmab vs ZA was based on a large head-to-head phase 3 trial (N=1,901). The real world SRE rate in ZA pts was derived from a large commercial claims database analysis (Hatoum, 2008). SRE QALY decrements were estimated using the time trade-off method (Matza, 2011). SRE costs were estimated from a nationally representative commercial claims database (Barlev, 2010). Wholesale acquisition drug cost (Analysource, 2011), drug administration, and renal monitoring costs (National Fee Analyzer, 2011) were included. Compliance and mortality were assumed to be the same in both groups. Costs and QALYs were discounted at 3% annually. Results: With a median pt survival of 1.7 years, Dmab reduced the number of SREs and increased pts’ QALY vs ZA. The lifetime cost/pt on Dmab was $7,430 higher than ZA. Cost/QALY gained was $65,134, commonly considered good value based on oncologists’ implied threshold in the US (Nadler, 2006). Cost/SRE avoided was $9,212. Conclusions: Dmab is cost-effective in preventing SREs in pts with CRPC and BM compared with ZA in the US. The overall value of Dmab is based on superior efficacy and more efficient administration. [Table: see text]

Cost-effectiveness of zoledronic acid (ZOL) versus denosumab (Dmab) in prevention of skeletal-related events (SREs) in metastatic breast cancer (mBC).

294 Background: Dmab has been approved in the US for prevention of SREs in mBC on the basis of the results of a phase III trial comparing Dmab vs. ZOL in mBC. In this trial, overall survival, disease progression, and serious adverse events (SAEs) were similar across treatments. The cost of a Dmab injection ($1650) is nearly 2x that of ZOLs ($887). This analysis assessed the cost effectiveness of Dmab vs. ZOL in mBC from a US managed care perspective. Methods: A literature-based Markov model was developed to estimate the survival, quality-adjusted life-years (QALYs), number and costs of SREs, and drug and administration (Dmab=$32.46; ZOL=$153.86) costs for patients (pts) receiving Dmab or ZOL. Inputs were selected to reproduce the phase III trial outcomes up to 28 months. QALYs were estimated by assigning utilities to health states (prior to SRE; SRE; post-SRE, and death). SRE-related costs and utilities were obtained from the literature. Per-event SRE costs ranged from $4,039 (vertebral fracture) to $20,734 (bone surgery). In sensitivity analysis, SAEs were included ($15,441/pt with a SAE). Future outcomes were discounted at 3%/year. Results: Dmab resulted in fewer SREs, more QALYs, and lower SRE-related costs, but higher drug-related and total costs vs. ZOL, resulting in an incremental cost of $6,884/pt (TABLE). The cost per QALY gained was $644,000 when excluding SAEs ($613,000/QALY when including SAEs). Conclusions: Dmab is predicted to result in an incremental cost/QALY gained &gt;$600,000. This high cost/QALY is due to the higher drug acquisition cost of Dmab, combined with the limited prevention of SREs and lack of overall survival/disease progression benefits vs. ZOL. The cost/QALY of Dmab is far higher than what is considered to be good value for a medical intervention ($50,000 to $100,000/QALY), thus raising questions regarding Dmab's value in mBC. [Table: see text]