Cost-effectiveness Of Zoledronic Acid Research Articles

Cost-effectiveness of zoledronic acid compared with sequential denosumab/alendronate for older osteoporotic women in Japan

SummaryAmong hypothetical cohorts of older osteoporotic women without prior fragility fracture in Japan, we evaluated the cost-effectiveness of two treatment strategies using a simulation model. Annual intravenous zoledronic acid for 3 years was cost-saving compared with biannual subcutaneous denosumab for 3 years followed by weekly oral alendronate for 3 years.PurposeOsteoporosis constitutes a major medical and health economic burden to society worldwide. Injectable treatments for osteoporosis require less frequent administration than oral treatments and therefore have higher persistence and adherence with treatment, which could explain better efficacy for fracture prevention. Although annual intravenous zoledronic acid and biannual subcutaneous denosumab are available, it remains unclear which treatment strategy represents a better value from a health economic perspective. Accordingly, we examined the cost-effectiveness of zoledronic acid for 3 years compared with sequential denosumab/alendronate (i.e., denosumab for 3 years followed by oral weekly alendronate for 3 years, making the total treatment duration 6 years) among hypothetical cohorts of community-dwelling osteoporotic women without prior fragility fracture in Japan at ages 65, 70, 75, or 80 years.MethodsUsing a previously validated and updated Markov microsimulation model, we obtained incremental cost-effectiveness ratios (Japanese yen [¥] (or US dollars [$]) per quality-adjusted life-year [QALY]) from the public healthcare and long-term care payer’s perspective over a lifetime horizon with a willingness-to-pay of ¥5 million (or $47,500) per QALY.ResultsIn the base case, zoledronic acid was cost-saving (i.e., more effective and less expensive) compared with sequential denosumab/alendronate. In deterministic sensitivity analyses, results were sensitive to changes in the efficacy of zoledronic acid or the cumulative persistence rate with zoledronic acid or denosumab. In probabilistic sensitivity analyses, the probabilities of zoledronic acid being cost-effective were 98–100%.ConclusionsAmong older osteoporotic women without prior fragility fracture in Japan, zoledronic acid was cost-saving compared with sequential denosumab/alendronate.

Cost-effectiveness of zoledronic acid and strontium-89 as bone protecting treatments in addition to chemotherapy in patients with metastatic castrate-refractory prostate cancer. (ISRCTN 12808747) TRAPEZE.

e16108 Background: Bony metastatic CRPC has a poor prognosis and high morbidity. TRAPEZE is a factorial RCT using 3 agents, docetaxel (D), zoledronic acid (ZA) and strontium-89 (Sr89). All have pal...

PCN67 Cost Effectiveness of Zoledronic Acid (ZOL) in Postmenopausal Women With Early Breast Cancer Receiving Adjuvant Letrozole From German and Italian Perspectives

In the ZO-FAST trial, postmenopausal women with early breast cancer (pmBCa) and a bone mineral density (BMD) T-score ≥–2 and receiving adjuvant Letrozole (2.5 mg/day) were randomized to either immediate ZOL (4 mg/6 months) treatment (“Upfront ZOL”) or to the same therapy but only when BMD T-score decreased to <−2 or fracture occurrence (“Delayed ZOL”). After 60 months, Upfront ZOL increased both BMD and disease-free survival (P<.05) relative to Delayed ZOL. The present analysis assessed the cost effectiveness of Upfront vs. Delayed ZOL in this population, from German (DE) and Italian (IT) payer perspectives. A Markov state-transition model was constructed to estimate the lifetime costs and QALY for hypothetical cohorts of pmBCa women receiving Letrozole with Upfront or Delayed ZOL. Consistent with ZO-FAST, at baseline, patients were 57 years old and BCa-recurrence free. Patients could progress over time to “Local Recurrence”, “Contralateral Tumor”, “Distant Recurrence”, or Death. Annual transition probabilities were derived from ZO-FAST, supplemented with literature estimates. Direct costs and utilities were literature-based. All results were discounted using country-specific rates. In IT, Upfront ZOL treatment was associated with 15.01 QALYs and €21 998. Delayed ZOL was associated with 13.98 QALYs and €19 458. Thus, Upfront ZOL cost €2 453/QALY. In DE, Upfront ZOL treatment resulted in 15.44 QALYs and €24 032. Delayed ZOL was associated with 14.37 QALYs and €23 081. Therefore, Upfront ZOL cost €888/QALY. In both countries, the results were very insensitive to changes in individual model input values. Compared to Delayed ZOL, Upfront ZOL treatment cost ≤€20 000/QALY in >95% of 1000 probabilistic sensitivity analysis model runs in both IT and DE. This analysis suggests that treatment with Upfront ZOL may reduce recurrence and increase QALY and is highly cost effective relative to a Delayed ZOL strategy from an IT and DE health care perspective.

Cost-effectiveness of zoledronic acid (ZOL) in postmenopausal women with early breast cancer receiving adjuvant letrozole.

553 Background: In the ZO-FAST trial, postmenopausal women with early breast cancer and a bone mineral density (BMD) T-score ≥ –2 and receiving adjuvant letrozole (2.5 mg/day) were randomized to either immediate ZOL (4 mg/6 months) treatment (upfront ZOL) or to the same therapy but only when BMD T-score decreased to &lt; –2 or fracture occurrence (delayed ZOL). After 60 months, upfront ZOL increased both BMD and disease-free survival (P &lt; .05) relative to delayed ZOL. The present analysis assessed, from a US payer perspective, the cost effectiveness of upfront ZOL vs delayed ZOL in this population. Methods: A Markov state-transition model was developed to estimate the lifetime costs and quality-adjusted life-years (QALYs) for a hypothetical cohort of postmenopausal women with early breast cancer receiving letrozole with upfront or delayed ZOL. Consistent with ZO-FAST, patients were 57 years of age and breast cancer recurrence-free at baseline. Patients could progress over time to Local Recurrence, Contra-lateral Tumor, Distant Recurrence, or Death. Transition probabilities were derived from ZO-FAST, supplemented with literature. Costs and utilities were literature based. All outcomes were discounted 3% per year. Results: Compared to delayed ZOL, upfront ZOL resulted in better overall survival, disease-free survival, and QALYs, but at a higher cost (Table). In the base case, the incremental cost/QALY gained with upfront vs delayed ZOL was $7,967. In &gt; 95% of 1,000 probabilistic sensitivity analysis runs, upfront ZOL costs less than $38,376/QALY gained. Conclusions: Upfront ZOL may increase survival and QALY and, at a cost per QALY well under the $50,000/QALY threshold, is very cost-effective in this population. [Table: see text]

Pharmacoeconomics of Bisphosphonates for Skeletal-Related Event Prevention in Metastatic Non-Breast Solid Tumours

Bisphosphonates reduce the risk of skeletal-related events (SREs; i.e. spinal cord compression, pathological fracture, radiation or surgery to the bone, and hypercalcaemia) in patients with metastatic cancer. A number of analyses have been conducted to assess the cost effectiveness of bisphosphonates in patients with bone metastases secondary to breast cancer, but few in other solid tumours. This is a review of cost-effectiveness analyses in patients with non-breast solid tumours and bone metastases. A literature search was conducted to identify cost-effectiveness analyses reporting the cost per QALY gained of bisphosphonates in patients with metastatic bone disease secondary to non-breast solid tumours. Four analyses met inclusion criteria. These included two in prostate cancer (one of which used a global perspective but expressed results in $US, and the other reported from a multiple country perspective: France, Germany, Portugal and the Netherlands). The remaining analyses were in lung cancer (in the UK, France, Germany, Portugal and the Netherlands), and renal cell carcinoma (in the UK, France and Germany). In each analysis, the cost effectiveness of zoledronic acid versus placebo was analysed. Zoledronic acid was found to be cost effective in all European countries across all three indications but not in the sole global prostate cancer analysis. Across countries and indications, assumptions regarding patient survival, drug cost and baseline utility (i.e. patient utility with metastatic disease but without an SRE) were the most robust drivers of modelled estimates. Assumptions of SRE-related costs were most often the second strongest cost driver. Further review indicated that particular attention should be paid to the inclusion or exclusion of nonsignificant survival benefits, whether health state utilities were elicited from community or patient samples or author assumptions, delineation between symptomatic and asymptomatic SREs, and the methods with which SRE disutility was modelled over time. While the field of cost-effectiveness analysis in solid tumours other than breast cancer is still evolving, outcomes will likely continue to be driven by drug cost and assumptions regarding treatment benefits. Although considerations such as adverse events and administration costs are important, they were not found to influence cost-effectiveness estimates greatly. As zoledronic acid will lose patent protection in 2013 and subsequently be greatly reduced in price, it is likely that the field of cost effectiveness will change with regard to SRE-limiting agents. Meanwhile, research should be conducted to improve our understanding of the impact on quality of life and medical costs of preventing SREs.

Cost-effectiveness of zoledronic acid vs clodronic acid for newly-diagnosed multiple myeloma from the United Kingdom healthcare system perspective

Objective:In the Medical Research Council Myeloma IX Study (MMIX), zoledronic acid (ZOL) 4 mg 3–4/week reduced the incidence of skeletal-related events (SREs), increased progression free survival (PFS), and prolonged overall survival (OS), compared with clodronic acid (CLO) 1600 mg daily, in 1970 patients with newly-diagnosed multiple myeloma (MM).Methods:An economic model was used to project PFS, OS, the incidence of SREs and adverse events and expected lifetime healthcare costs for patients with newly-diagnosed MM who are alternatively assumed to receive ZOL or CLO. The incremental cost-effectiveness ratio [ICER] of ZOL vs CLO was calculated as the ratio of the difference in cost to the difference in quality-adjusted life years (QALYs). Model inputs were based on results of MMIX and published sources.Results:Compared with CLO, treatment with ZOL increases QALYs by 0.30 at an additional cost of £1653, yielding an ICER of £5443 per QALY gained. If the threshold ICER is £20,000 per QALY, the estimated probability that ZOL is cost-effective is 90%.Limitations:The main limitation of this study is the lack of data on the effects of zoledronic acid on survival beyond the end of follow-up in the MMIX trial. However, cost-effectiveness was favourable even under the highly conservative scenario in which the timeframe of the model was limited to 5 years.Conclusions:Compared with clodronic acid, zoledronic acid represents a cost-effective treatment alternative in patients with multiple myeloma.

PCN73 Cost Effectiveness of Zoledronic Acid vs. Pamidronate or No therapy for the Treatment of Bone Metastases Secondary to Prostate Cancer

Zoledronic acid (ZOL) is the only approved bisphosphonate for SRE prevention in hormone-refractory prostate cancer (mHRPC). However, in the UK (UK), 19% and 4% of metastatic, mHRPC patients, do not receive bisphosphonates or receive non-approved/unproven bisphosphonates (i.e., pamidronate [PAM]), respectively for the prevention of skeletal-related events (SREs). This analysis sought to estimate, from a UK payer perspective, the cost effectiveness of providing ZOL to those mHRPC patients not receiving ZOL. This analysis was based on the results of a published randomized phase III clinical trial wherein mHRPC patients received ≤15 months of ZOL or placebo (PBO) (Saad et al, 2002). Since PAM has been shown to be no different than PBO in mHRPC in a pooled analysis of two trials (Small et al 2003) (i.e., 25% of subjects experienced an SRE at 6 months), the PBO cohort data from the ZOL trial was as a surrogate for PAM data in the absence of a direct comparison of ZOL versus PAM (or other bisphosphonates). Costs were estimated using hospital tariffs and published/internet sources. Quality adjusted life years (QALYs) gained were based on a previously published analysis of the Saad et al (2002) data. Survival was assumed to be identical for both groups. Compared with the use of PAM/PBO, treatment with ZOL (at list price of £174.14/infusion vs £80/infusion with PAM) resulted in increased QALYs (+0.03566/pt), fewer SREs (-0.8314/pt, i.e., 0.8315 vs 1.6629), and fewer SRE-related costs (-£1,639/pt, i.e., £2,004 vs. £3,643). Total costs were higher with ZOL (+£702/pt). ZOL cost £19,689/QALY. The use of ZOL for the prevention of SREs in UK patients with bone metastases secondary to mHRPC is cost effective relative to providing no or unapproved bisphosphonates.

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]

Cost-effectiveness of zoledronic acid (ZOL) versus denosumab (Dmab) in prevention of skeletal-related events (SREs) in castration-resistant prostate cancer metastatic to the bone (mCRPC).

4581 Background: A phase III trial found that Dmab reduced the proportion of mCRPC patients (pts) developing ≥1 SREs by 4.7 absolute percentage points vs. ZOL (from 40.6% to 35.9%). However, overall survival, disease progression, serious adverse events, and bone pain were similar across treatments. In the United States (US), the acquisition cost of Dmab ($1650) per injection is nearly 2x that of ZOL’s ($887). This analysis assessed the cost-effectiveness of Dmab vs. ZOL in mCRPC 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 mCRPC pts receiving Dmab or ZOL for 27 months. Model inputs were selected to reproduce the phase III trial outcomes. QALYs were estimated by assigning utilities to health states (prior to SRE; SRE; post-SRE, and death). Cost for individual SREs ranged from $4,039 to $20,734. Future outcomes were discounted at 3%/year. Results: Compared to ZOL (Table), Dmab resulted in fewer SREs, more QALYs, and lower SRE-related costs, but higher drug-related and total costs ($5,313). Overall, Dmab resulted in an incremental cost of $1,250,000 per QALY gained. Conclusions: The use of Dmab in mCRPC is predicted to result in an incremental cost per QALY gained of $1.25 million. This high cost per QALY is attributed to Dmab having a higher drug acquisition cost, limited prevention of SREs, and no additional overall survival or disease progression benefits vs. ZOL. The cost per QALY of Dmab in this setting is far higher than what is considered in the US to be good value for a medical intervention ($50,000 to $100,000 per QALY), thus raising questions about the value of using Dmab in mCRPC. ZOL Dmab Difference SREs/pt 1.29 1.04 -0.25 Discounted QALYs/pt 0.93 0.94 +0.00493 Discounted costs Drug, administration, monitoring $12,963* $20,277 $+7,313 SREs $9,528 $7,604 $-1,924 Total $22,491 $27,881 +5,390 Cost/QALY gained $1,248,051 * Costs in 2010 U.S. dollars.

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

9025 Background: Dmab has been approved in the United States 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 ($1,650) is nearly 2x that of ZOL’s ($887). This analysis assessed the cost effectiveness of Dmab vs. ZOL in mBC from a U.S. 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 >$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. ZOL Dmab Difference Cumulative SREs/pt 1.010 0.694 -0.317 Total discounted QALYs/pt 0.9405 0.9512 +0.0107 Discounted costs Drug, administration, monitoring $15,994 $25,016 +$9,023 SREs $7,290 $5,152 -$2,138 Total $21,284 $30,168 +$6,884 Cost/QALY gained $643,726 Costs in 2010 U.S. dollars.

Cost-Effectiveness of Zoledronic Acid in the Management of Skeletal Metastases in Patients With Lung Cancer in France, Germany, Portugal, The Netherlands, and the United Kingdom

Background Zoledronic acid (ZOL) significantly reduces the risk of new skeletal-related events (SREs) in patients with non–small cell lung cancer (NSCLC) who have bone metastases. Objective The purpose of this study was to assess the cost and cost-effectiveness of ZOL in the management of skeletal metastases in this population across 5 European countries (France, Germany, United Kingdom, Portugal, and the Netherlands) from the perspective of national health care. Methods This cost-effectiveness analysis was based on a subset of patients with NSCLC who were enrolled in a Phase III trial of patients with bone metastases secondary to a variety of solid tumors. In this trial, patients were randomized to receive ZOL or placebo every 3 weeks for up to 21 months. Survival, SRE incidence, and number of infusions administered were derived from the clinical trial. Costs of SREs were estimated using hospital Diagnosis Related Group tariffs and published data. Drug, drug administration, and supply costs were obtained from published and internet sources. Quality-adjusted life-years (QALYs) were estimated based on the published utilities and modeled survival and frequency of SREs. Uncertainty surrounding outcomes was addressed via univariate and probabilistic sensitivity analyses. Results Compared with patients receiving placebo (n = 120), patients receiving ZOL (n = 124) experienced an estimated 0.79 fewer SREs and gained an estimated 0.02 QALYs. ZOL use in patients with NSCLC and bone metastases was associated with a reduction in SRE costs (ranging from €1547 to €1893 [2007–2008 €], depending on the country). After adding drug and drug administration costs, ZOL use resulted in a net savings of €288 per patient in Germany, €209 in the United Kingdom, and €113 in Portugal. In France and the Netherlands, costs increased (€17 and €178, respectively), but the costs per QALY gained were low (€786 and €8278, respectively). In univariate sensitivity analyses, the cost per QALY for ZOL versus placebo was ≤€50,000 for all scenarios tested. The results were most sensitive to assumptions regarding survival, number of ZOL infusions, and the costs of SREs. The probabilistic sensitivity analysis indicated that ZOL cost ≤€50,000 per QALY in 65% to 83% of model simulations (depending on country). However, some degree of uncertainty remained as the 95th percentile of cost per QALY was high. Conclusions This analysis is subject to the usual limitations of cost-effectiveness models, which combine assumptions and data from multiple sources. Nevertheless, based on the assumptions used herein, the present model suggests that ZOL increases QALYs and is cost saving and/or cost effective compared with placebo in patients with NSCLC in France, Germany, the United Kingdom, Portugal, and the Netherlands.

The cost effectiveness of zoledronic acid 5 mg for the management of postmenopausal osteoporosis in women with prior fractures: evidence from Finland, Norway and the Netherlands

Objective:This study was conducted to assess the cost effectiveness of zoledronic acid 5 mg as a first-line treatment for the secondary prevention of fragility fractures in women with postmenopausal osteoporosis in Finland, Norway and the Netherlands.Methods:A discrete-event, individual-patient computer-simulation model was used to compare the cost effectiveness of zoledronic acid with that of basic treatment (calcium and vitamin D) and commonly prescribed bisphosphonates in postmenopausal women aged 50–80 years who have experienced one previous fracture and have a bone mineral density T-score of −2.5.Results:The cost per quality-adjusted life-year (QALY) gained with zoledronic acid compared with basic treatment ranged from being cost saving in all age groups in Norway, to costing approximately €19,000 in Finland and €22,300 in the Netherlands. Compared with the other branded bisphosphonates, zoledronic acid was cost saving in many scenarios, including all age groups in Finland. In Norway, zoledronic acid dominated branded risedronate and ibandronate in all age groups and dominated or had incremental cost-effectiveness ratios (ICERs) of up to NOK83,954 per QALY gained compared with branded alendronate. In the Netherlands, zoledronic acid dominated branded intravenous ibandronate in all age groups; compared with branded risedronate and oral ibandronate, zoledronic acid dominated or had ICERs of up to €4832 per QALY gained; compared with branded alendronate, it had ICERs of up to €48,383 per QALY gained. In all three countries, zoledronic acid may be cost effective compared with generic alendronate when patient compliance with drug therapy is taken into account. Sensitivity analyses showed that the model was robust to changes in key values. The main model limitations were the lack of real-life compliance and persistence data, and lack of country-specific data for some parameters.Conclusions:Using local or commonly used thresholds, this analysis suggests that zoledronic acid would be a cost-effective first-line option compared with other branded bisphosphonates and, in some scenarios, compared with generic alendronate, for the secondary prevention of fractures in women with postmenopausal osteoporosis in Finland, Norway and the Netherlands.

Cost effectiveness of zoledronic acid in the management of skeletal metastases in hormone-refractory prostate cancer patients in France, Germany, Portugal, and the Netherlands

Objective:Zoledronic acid (ZOL) reduces the risk of skeletal related events (SREs) in hormone-refractory prostate cancer (HRPC) patients with bone metastases. This study assessed the cost effectiveness of ZOL for SRE management in French, German, Portuguese, and Dutch HRPC patients.Methods:This analysis was based on the results of a randomized phase III clinical trial wherein HRPC patients received up to 15 months of ZOL (n = 214) or placebo (n = 208). Clinical inputs were obtained from the trial. Costs were estimated using hospital tariffs, published, and internet sources. Quality adjusted life-years (QALYs) gained were estimated from a separate analysis of EQ-5D scores reported in the trial. Uncertainty surrounding outcomes was addressed via univariate sensitivity analyses.Results:ZOL patients experienced an estimated 0.759 fewer SREs and gained an estimated 0.03566 QALYs versus placebo patients. ZOL was associated with reduced SRE-related costs [net costs] (−€2396 [€1284] in France, −€2606 [€841] in Germany, −€3326 [€309] in Portugal and −€3617 [€87] in the Netherlands). Costs per QALY ranged from €2430 (Netherlands) to €36,007 (France).Conclusions:This analysis is subject to the limitations of most cost-effectiveness analyses: it combines data from multiple sources. Nevertheless, the results strongly suggest that ZOL is cost effective versus placebo in French, German, Portuguese, and Dutch HRPC patients.

Cost-effectiveness of zoledronic acid in the prevention of skeletal-related events in patients with bone metastases secondary to advanced renal cell carcinoma: application to France, Germany, and the United Kingdom.

BackgroundThe use of zoledronic acid (ZOL) has recently been shown to significantly reduce the risk of new skeletal-related events (SREs) in renal cell carcinoma (RCC) patients with bone metastases. The present exploratory study assessed the cost-effectiveness of ZOL in this population, adopting a French, German, and United Kingdom (UK) government payer perspective.Materials and methodsThis cost-effectiveness model was based on a post hoc retrospective analysis of a subset of patients with RCC who were included in a larger randomized clinical trial of patients with bone metastases secondary to a variety of cancers. In the trial, patients were randomized to receive ZOL (n = 27) or placebo (n = 19) with concomitant antineoplastic therapy every 3 weeks for 9 months (core study) plus 12 months during a study extension. Since the trial did not collect costs or data on the quality-adjusted life years (QALYs) of the patients, these outcomes had to be assumed via modeling exercises. The costs of SREs were estimated using hospital DRG tariffs. These estimates were supplemented with literature-based costs where possible. Drug, administration, and supply costs were obtained from published and internet sources. Consistent with similar economic analyses, patients were assumed to experience quality of life decrements lasting 1 month for each SRE. Uncertainty surrounding outcomes was addressed via multivariate sensitivity analyses.ResultsPatients receiving ZOL experienced 1.07 fewer SREs than patients on placebo. Patients on ZOL experienced a gain in discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the UK. Discounted SRE-related costs were substantially lower among ZOL than placebo patients (−€ 4,196 in France, −€ 3,880 in Germany, and −€ 3,355 in the UK). After taking into consideration the drug therapy costs, ZOL saved € 1,358, € 1,223, and € 719 in France, Germany, and the UK, respectively. In the multivariate sensitivity analyses, therapy with ZOL saved costs in 67–77% of simulations, depending on the country. The cost per QALY gained for ZOL versus placebo was below € 30,000 per QALY gained threshold in approximately 93–94% of multivariate sensitivity analyses simulations.ConclusionsThe present analysis suggests that ZOL saves costs and increases QALYs compared to placebo in French, German, and UK RCC patients with bone metastases. Additional prospective research may be needed to confirm these results in a larger sample of patients.

Cost-effectiveness of zoledronic acid (ZOL) for the treatment of bone loss in postmenopausal women with early-stage breast cancer receiving aromatase inhibitors in the United States (US).

e11007 Background: Treatment guidelines recommend the use of bisphosphonates in postmenopausal women with early-stage breast cancer receiving prolonged aromatase inhibitor therapy and who are at high risk of fractures (e.g., in patients whose bone loss has become clinically significant, e.g., with bone mineral density BMD T score < 2 SD below normal, or who have experienced a fragility fracture). This retrospective modeling analysis assessed the cost-effectiveness of ZOL therapy versus no therapy for the treatment of aromatase inhibitor induced bone loss in US postmenopausal women with breast cancer. Methods: A model was developed to project the lifetime fractures incidence as a function of BMD. In the model, patients were assumed to receive aromatase inhibitors (i.e., letrozole [Femara] 2.5 mg daily), for 5 years with a starting T score of -2 or more. In one arm, patients initiated ZOL (4 mg IV infusion q 6 months) when their BMD T-score decreased to more than 2 SD below normal or had nontraumatic fracture. Data regarding the efficacy of this treatment arm came from the results of the US- based Z-FAST trial. In the comparison group, patients were assumed to receive no ZOL therapy. The progression of bone loss and risk of fracture in the no treatment group were obtained from the published epidemiologic literature. The model simulated the impact of fractures on costs, quality of life and mortality. Results: Compared to the no treatment arm, patients on the ZOL arm experienced a gain of 0.032 quality-adjusted life-years (QALYs), at the incremental costs of $47,995 per QALY. In a sensitivity analysis in which a Medicare payer perspective was adopted, whereby only 80% of costs are included, the costs/QALY improved to $38,396. Conclusions: The use of ZOL for the treatment of aromatase inhibitor induced bone loss in postmenopausal women with breast cancer whose bone loss has become clinically significant or who have experienced a fragility fracture appears cost-effective in the US. These results might be conservative as they exclude the potential benefits of ZOL on disease progression. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis

Cost-effectiveness of zoledronic acid in the prevention of skeletal-related events in patients with bone metastases from renal cell carcinoma: Comparison between France, Germany, and the United Kingdom

5106 Background: Zoledronic acid (ZOL) significantly reduces the risk of new skeletal-related events (SREs) in patients (pts) with bone metastases from RCC. This study assessed and compared the cost-effectiveness of ZOL in pts with RCC from French, German, and United Kingdom (UK) societal perspectives. Methods: This analysis was based on a retrospective analysis of RCC pts with bone metastases who were enrolled in a 9-mo trial of ZOL or placebo (PBO) plus concomitant antineoplastic therapy. A model was developed to simulate costs and quality-adjusted life-years (QALYs) experienced by study pts. The model included data and assumptions regarding SRE incidence, mortality, drug and administration costs, SRE costs, reduced quality of life (QOL) because of SREs and bone pain, and therapy duration. SRE costs were estimated using diagnosis-related group tariff information and published literature. Consistent with similar economic analyses, it was assumed that QOL decreased 20% to 80% (depending on SRE type) for 1 mo after each SRE experienced. Sensitivity analyses were performed to test the effects of alternate assumptions, with &lt; 30,000/QALY considered cost-effective. Results: Compared with PBO-treated pts (n = 19), ZOL-treated pts (n = 27) experienced 1.07 fewer SREs/pt and gained discounted QALYs of approximately 0.1563 in France and Germany and 0.1575 in the UK. Discounted SRE-related costs were substantially lower among pts treated with ZOL vs PBO (-4,196 in France, -3,880 in Germany, and -3,355 in the UK). After including drug therapy costs, ZOL saved 1,358, 1,223, and 719 per pt in France, Germany, and the UK, respectively. In multivariate sensitivity analyses, ZOL saved costs in 67% to 77% of cases, depending on the country. ZOL resulted in a cost per QALY gained &lt; 30,000 in approximately 93% of cases. Conclusions: Treatment with ZOL reduces SREs, improves QOL, and lowers health-related costs compared with PBO in French, German, and UK pts with bone metastases from RCC. Use of ZOL in these populations therefore provides health-related cost savings and is a cost-effective use of healthcare resources. [Table: see text]

Cost-effectiveness of zoledronic acid plus endocrine therapy in premenopausal women with early stage breast cancer based on results of the ABCSG-12 study.

Abstract Abstract #2112 Background: Zoledronic acid (ZOL) has demonstrated antitumor and antimetastatic activity in preclinical and early clinical studies. The Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12) examined the efficacy of ovarian suppression using goserelin combined with 3 years of endocrine therapy (ET) with anastrozole (ANA) or tamoxifen (TAM) with or without ZOL (4 mg q6m) in 1803 premenopausal women with endocrine-responsive early breast cancer. After a median follow-up of 47.8 months, there was no significant difference (p&amp;gt;0.05) between patients who received TAM vs. ANA in disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS). However, the addition of ZOL to ET significantly reduced the risk of DFS events by 36% (HR = 0.64, p = 0.011) and RFS by 35% (HR=0.65, p=0.014) compared with ET alone. There was a nonsignificant trend in OS favoring ZOL (p= 0.101). ZOL was generally well tolerated, and there were no confirmed cases of ONJ or renal toxicity.&amp;#x2028; Methods: A Markov model was used to generate preliminary estimates the cost-effectiveness (cost per quality adjusted life year [QALY] gained) of 3 years of ZOL+ET compared to 3 years of ET alone, in premenopausal women with early stage breast cancer. A lifetime timeframe was employed. Probabilities of recurrence with ZOL+ET and ET alone were based on the results of ABCSG-12 trial (ASCO 2008; #LBA4). Outcomes after recurrence were based on published studies and assumed to be the same for ZOL+ET and ZOL only. A US healthcare system perspective was employed. Costs of study medications were based on wholesale acquisition costs. Costs of ZOL administration were based on Medicare fees. Costs of breast cancer care were based on published sources. Costs and QALYs were discounted at 3% annually. Results were generated under 2 scenarios regarding duration of benefit (reduction in risk of recurrence) with ZOL: (1) benefits persist until death (“lifetime benefit scenario”): (2) benefits persist to the maximum follow-up reported for ABCSG-12 (84 months) (“trial benefit scenario”).&amp;#x2028; Results: The additional cost of 3 years of ZOL 4 mg q6m is approximately $5,000 (including drug administration costs). Under the lifetime benefit scenario, the additional costs of ZOL are more than offset by savings in costs of recurrences, and ZOL+ET is the “dominant strategy”, reducing total costs while increasing QALYs. Under the trial benefit scenario, the additional costs of ZOL are partially offset by savings in the costs of recurrences. However, the cost effectiveness of ZOL+ET vs. ET only is highly favorable (i.e., &amp;lt;$10,000 per QALY gained).&amp;#x2028; Conclusion: In premenopausal women with early stage breast cancer, adding zoledronic acid to adjuvant endocrine therapy is likely to be cost-effective use of healthcare resources from a US healthcare system perspective. Further analyses are ongoing to refine these estimates and examine sensitivity of model results to key assumptions and parameter estimates. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2112.

Cost effectiveness of zoledronic acid in the prevention of skeletal related events in renal cell carcinoma patients with bone metastases: An exploratory analysis for France

16085 Background: Previous European analyses have shown that zoledronic acid (ZOL) is cost effective in patients with bone metastases secondary to breast cancer, lung cancer, and other solid tumors. A recent analysis suggests that ZOL significantly reduce the risk of new skeletal related events (SREs) such as spinal cord compression, pathological fracture, radiation or surgery to bone, in renal cell carcinoma (RCC) patients with bone metastases. The present study assessed the cost effectiveness of ZOL in this population, adopting a French health care payer perspective. Methods: This analysis was based on a retrospective analysis of a trial of ZOL which randomized RCC patients with bone metastases to ZOL (n=27) or placebo (n=19) plus concomitant antineoplastic therapy for 9 months. A model was developed to simulate the costs and quality-adjusted life-years (QALYs) of the trial patients. SRE costs were estimated by pooling data from SRE studies in the Netherlands and Portugal. These estimates were supplemented with literature-based costs. Drug costs were obtained from French tariffs. Consistent with similar economic analyses, it was assumed that quality of life decreased for 1 month after each SRE experienced. Uncertainty was addressed via bootstrapping and multivariate probabilistic sensitivity analyses (PSA), which involved 10,000 model simulations using input values drawn from probability distributions. Results: ZOL and placebo patients experienced an estimated 0.527 vs. 0.402 discounted QALYs, respectively. Discounted SRE-related costs were substantially lower among ZOL than placebo patients (€3,754 v. €10,531, respectively). After taking into consideration drug therapy costs, ZOL saved €4,732 and increased QALYs by 0.125. Thus, ZOL is preferred over placebo both in terms of costs and quality of life. In the PSA, therapy with ZOL saved costs in 93% of simulations. The cost per QALY gained was below the €50,000 per QALY gained threshold in 97% of PSA simulations. Conclusions: The present analysis suggests that ZA is cost saving and increases QALYs compared to placebo in RCC patients with bone metastases in France. These results may need to be confirmed via a larger prospective clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis

No bones about the cost effectiveness of zoledronic acid

No bones about the cost effectiveness of zoledronic acid

No bones about the cost effectiveness of zoledronic acid

No bones about the cost effectiveness of zoledronic acid