Retrospective evaluation of the clinical benefit of long-term continuous use of zoledronic acid in patients with lung cancer and bone metastases

Abstract

Background:

For patients with bone metastases, skeletal-related events including fracture are common, can cause considerable morbidity, and may reduce overall survival (OS). This retrospective analysis assessed the effect of Zometa (zoledronic acid, ZOL), an intravenous bisphosphonate (IV-BP), on fracture risk and OS in patients with bone metastases from lung cancer (LC). (Zometa is a registered trademark of Novartis Pharmaceuticals Corporation, USA.)

Methods:

A claims-based analysis using commercial and Medicare Advantage data from >45 US managed-care plans was used to evaluate the association between fracture risk and treatment persistency (31–90, 91–180, 181–365, and ≥366 days) and follow-up duration in LC patients diagnosed with bone metastases between 01/01/2001 and 12/31/2006 and treated with ZOL or without (no IV-BP). Persistency was defined as the absence of a >45-day gap between ZOL treatments. Analysis of variance tests were used to compare follow-up duration, a proxy for OS, between ZOL persistency groups. The effect of time to treatment with ZOL was also assessed.

Results:

In 9874 LC patients with bone metastases (n?=?1090 ZOL; n?=?8784 no IV-BP) the unadjusted relative fracture risk was reduced by 40% with ZOL vs no IV-BP; fracture risk decreased consistently with increasing duration of ZOL treatment. Even short-term (31–90 days) ZOL significantly reduced fracture risk (47%) vs no IV-BP (p?=?0.005) with adjustment for differences in demographic and clinical characteristics. Delaying ZOL until after bone metastases were diagnosed significantly increased fracture risk (p?=?0.0017). For a sub-set of patients included in a survival analysis (n?=?550 ZOL; n?=?4512 no IV-BP), mortality was significantly lower (mean, 38.6 vs 46.8 deaths/100 person-years; p?=?0.038) in those treated with ZOL vs no IV-BP.

Limitations:

Interpretation of this claims-based analysis must be tempered by the inherent limitations of observational data, such as limited clinical information and the ability to control for prognostic factors.

Conclusions:

This retrospective analysis demonstrates that LC patients with bone metastases receiving ZOL had significantly reduced risk of fracture (p?=?0.005) and death (p?<?0.038) vs patients receiving no IV-BP. Longer ZOL persistency consistently yielded better outcomes, with ≥12 months’ treatment producing the greatest benefit.     

Burden of breast cancer with brain metastasis: a French national hospital database analysis

Abstract

Objective:

Incidence of breast cancer with brain metastases (BCBM) is increasing, especially among patients over-expressing HER2. Epidemiology on this sub-type of cancer is scarce, since cancer registries carry no information on the HER2 status. A retrospective database analysis was conducted to estimate the burden of BCBM, especially among HER2-positive patients in a secondary objective.

Methods:

Patients with a new diagnosis of BCBM carried out between January and December 2008 were identified from the national hospital database using the International Disease Classification. Patients receiving a targeted anti-HER2 therapy were identified from the national pharmacy database. Hospital and pharmacy claims were linked to estimate the burden of HER2-positive patients. Data on hospitalizations were extracted to describe treatment patterns and healthcare costs during a 1-year follow-up. Predictors of treatment cost were analyzed through multi-linear regression analysis.

Results:

Two thousand and ninety-nine BCBM patients were identified (mean age (SD)?=?57.8 (13.6)), of whom 12.2% received a targeted anti-HER2 therapy; 79% of patients had brain metastases associated with extracranial metastases, and the attrition rate reached 82%. Patients received mostly palliative care (47.4%), general medical care (40.6%), and chemotherapy (35.0%). The total annual hospital cost of treatment was 8,426,392€, representing a mean cost of 22,591€ (±14,726) per patient, mainly influenced by extracranial metastases, surgical acts, and HER2-overexpression (p?<?0.0001).

Conclusions:

The database linkage of hospital and pharmacy claims is a relevant approach to identify sub-type of cancer. Chemotherapy was widely used as a systemic treatment for breast cancer rather than for local treatment of brain metastases whose morbi-mortality remains high. The variability of treatment costs suggests clinical heterogeneity and, thus, extensive individualization of protocols.     

Annual cost of hospitalization,inpatient rehabilitation and sick leave of anal cancer in Germany

Abstract

Objective:

Literature on the economic burden of anal cancer in Germany is scarce. About 84% of these cancers are associated with human papillomavirus infection. This study, therefore, aimed to assess the annual costs of human papillomavirus-related anal cancer incurred by hospitalization, inpatient rehabilitation, and sick leave in 2008 in Germany.

Methods:

A cross-sectional retrospective analysis of five German databases covering hospital treatment, inpatient rehabilitation, and sick leave in 2008 was performed. All hospital, inpatient rehabilitation, and sick leave cases due to anal cancer in 2008 were analyzed. Associated numbers of anal cancer hospitalizations, healthcare resource use, and costs were identified and extracted using the ICD-10 code C21 as the main diagnosis. The annual cost of human papillomavirus-related anal cancer was estimated based on the percentage of anal cancer likely to be attributable to human papillomavirus.

Results:

In 2008, there were 5774 hospitalizations (39% males, 61% females), 517 inpatient rehabilitations, and 897 sick leaves due to anal cancer representing costs of €34.11 million. The estimated annual costs associated with human papillomavirus-related anal cancer were €28.72 million, mainly attributed to females (62%). Direct costs accounted for 90% (86% for hospital treatment, 4% for inpatient rehabilitation) and indirect costs due to sick leave accounted for 10% of human papillomavirus-related costs.

Conclusions:

The economic burden of human papillomavirus-related anal cancer in 2008 in Germany is under-estimated, since costs incurred by outpatient management, outpatient chemotherapy, long-term care, premature retirement, and premature death were not included. However, this study is the first analysis to investigate the economic burden of anal cancer in Germany. The estimated annual costs of human papillomavirus-related anal cancer contribute to a significant economic burden in Germany and should be considered when assessing health and economic benefits of human papillomavirus vaccination in both genders.     

Corroboration of claims algorithm for second-line costs of metastatic colorectal cancer treatment with targeted agents

Abstract

Objective:

To refine a claims algorithm for identifying second-line systemic regimens for metastatic colorectal cancer (mCRC) based on clinical evidence and to compare costs during second-line treatment by targeted therapy administered.

Methods:

This retrospective analysis of a large US managed care database identified patients diagnosed with mCRC during 1 July 2007–30 June 2011. A claims-based algorithm was developed to identify patients with at least two lines of therapy (LOT) and the second LOT contained one targeted agent: bevacizumab or any anti-epidermal growth factor receptor (EGFR). Medical chart data from 92 patients were used to corroborate and refine the LOT algorithm. The positive predictive value (PPV) of the initial algorithm and refined algorithm for identification of second LOT are presented. The final algorithm was applied to claims data and two mutually exclusive second-line cohorts were examined: patients with bevacizumab- or cetuximab-containing regimens. Second-line healthcare costs were analyzed with generalized linear models adjusted for demographic and clinical characteristics.

Results:

The PPV increased from 50.0% (95% CI?=?39.4–60.6) for the initial algorithm to 72.1% (95% CI?=?59.2–82.9) for the final algorithm. Mean age in the cohorts (n?=?569) was 61 years; 58% were men. Days of therapy were similar for the bevacizumab (n?=?450) vs cetuximab (n?=?119) cohorts, respectively: 131 vs 148 in first LOT and 123 (both cohorts) in second LOT (p?≥?0.27). Total costs during second-line treatment in the bevacizumab cohort were lower by $12,318 (p?=?0.02) and medical costs were lower by $13,809 (p?=?0.01). Monthly total and medical costs were lower by $2728 (p?=?0.03) and $3133 (p?=?0.01), respectively. Results are based on commercially or Medicare-insured patients and may not be generalizable to Medicaid or uninsured patients.

Conclusions:

Corroboration of claim-based algorithms with medical chart data improved algorithm performance. Second-line total and medical costs were lower for mCRC patients treated with bevacizumab compared with cetuximab.     

Economic evaluation of extended and conventional prophylaxis with enoxaparin against venous thromboembolism in patients undergoing surgery for abdominal cancer

Summary

This study assesses the cost-effectiveness of extended enoxaparin prophylaxis (EEP) and conventional enoxaparin prophylaxis (CEP) compared with conventional unfractionated heparin prophylaxis (CUP) against venous thromboembolism (VTE) in patients undergoing surgery for abdominal cancer.

A decision tree model compared CEP (enoxaparin 40 mg once daily for 8±2 days), EEP (CEP plus 21 days outpatient prophylaxis with enoxaparin 40 mg once daily), and CUP (unfractionated heparin (UFH) 5,000 IU three times daily for 8±2 days). The primary effectiveness measure was symptomatic VTE. Secondary effectiveness measures included life-years gained.

CEP was associated with reduced costs and similar rates of symptomatic VTE compared with UFH. The cost per life year gained with EEP was estimated to be £15,200 compared with UFH and £22,700 compared with CEP.

Extended prophylaxis reduces symptomatic VTE events but increases cost. In patients undergoing surgery for abdominal malignancy, conventional prophylaxis with enoxaparin 40 mg once daily was found to be at least as effective as UFH, and cost saving at current prices.     

Economic impact of different preparations of leuprolide acetate in the management of advanced prostate cancer

This study aimed to compare the economic impact of 1-,3-and 6-monthly preparations of leuprolide acetate, a luteinising hormone-releasing hormone agonist (LHRHa), in the treatment of prostate cancer.

Using three published open-label multicentre clinical trials involving the use of each of the three LHRHa preparations, a cost minimisation analysis was undertaken.

The mean annual costs of managing advanced prostate cancer patients with the 1-,3-and 6-monthly preparations were e2,839 (standard deviation (sd) e233), e1,777 (sd e1 95) and e1,567 (sDe204), respectively.

The study concludes that, despite a higher unit price, use of the 6-monthly formulation of leuprolide acetate provides the lowest cost treatment option, the cost driver being the reduction in the number of treatments required. Germany was used as a case study to highlight the impact of health policies on the adoption of such cost optimisation treatment options in prostate cancer patients.     

Cost-minimization analysis of panitumumab compared with cetuximab for first-line treatment of patients with wild-type RAS metastatic colorectal cancer

Abstract

Objective:

To compare the costs of first-line treatment with panitumumab?+?FOLFOX in comparison to cetuximab?+?FOLFIRI among patients with wild-type (WT) RAS metastatic colorectal cancer (mCRC) in the US.     

Budget impact analysis of comprehensive genomic profiling in patients with advanced non-small cell lung cancer

Aims: Broad molecular profiling of patients with advanced non-small cell lung cancer (NSCLC) is strongly advised to optimize genomic matching with available targeted treatment options or investigational agents. Unlike conventional molecular diagnostic testing, or smaller hotspot panels, comprehensive genomic profiling (CGP) identifies genomic alterations across hundreds of clinically relevant cancer genes from a single tissue specimen. The present study sought to estimate the budget impact of increased use of CGP using a 324-gene panel (FoundationOne) vs non-CGP (represented by a mix of conventional molecular diagnostic testing and smaller NGS hotspot panels) and the number needed to test with CGP to gain 1 life year.

Materials and methods: A decision analytic model was developed to assess the budget impact of increased CGP in advanced NSCLC from a US private payer perspective. Model inputs were based on published literature (epidemiology and treatment outcomes), real-world data (testing and rates, medical service costs), list prices for CGP and anti-cancer drugs, and assumptions for clinical trial participation.

Results: Among 2 million covered lives, 532 had advanced NSCLC; 266 underwent molecular diagnostic testing. An increase in CGP among those tested, from 2% to 10%, was associated with $0.02 per member per month budget impact, of which $0.013 was attributable to costs of prolonged drug treatment and survival and $0.005 to testing cost. Approximately 12 patients would need to be tested with CGP to add 1 life year.

Limitations: The model incorporated certain assumptions to account for inputs with a limited evidence profile and simplify the possible post-CGP treatments.

Conclusions: An increase in CGP utilization from 2% to 10% among patients with advanced NSCLC undergoing molecular diagnostic testing was associated with a modest budget impact, most of which was attributable to increased use of more effective treatments and prolonged survival.     

Cost of adverse events during treatment with everolimus plus exemestane or single-agent chemotherapy in patients with advanced breast cancer in Western Europe

Objective:

Treatment options for recurrent or progressive hormone receptor-positive (HR+) advanced breast cancer include chemotherapy and everolimus plus exemestane (EVE?+?EXE). This study estimates the costs of managing adverse events (AEs) during EVE?+?EXE therapy and single-agent chemotherapy in Western Europe.

Methods:

An economic model was developed to estimate the per patient cost of managing grade 3/4 AEs for patients who were treated with EVE?+?EXE or chemotherapies. AE rates for patients receiving EVE?+?EXE were collected from the phase III BOLERO-2 trial. AE rates for single-agent chemotherapy, capecitabine, docetaxel, or doxorubicin were collected from published clinical trial data. AEs with at least 2% prevalence for any of the treatments were included in the model. A literature search was conducted to obtain costs of managing each AE, which were then averaged across Western European countries (when available). Per patient costs for managing AEs among patients receiving different therapies were reported in 2012 euros (€).

Results:

The EVE?+?EXE combination had the lowest average per patient cost of managing AEs (€730) compared to all chemotherapies during the first year of treatment (doxorubicin: €1230; capecitabine: €1721; docetaxel: €2390). The most costly adverse event among all patients treated with EVE?+?EXE was anemia (on average €152 per patient). The most costly adverse event among all patients treated with capecitabine, docetaxel, or doxorubicin was lymphocytopenia (€861 per patient), neutropenia (€821 per patient), and leukopenia (€382 per patient), respectively.

Conclusions:

The current model estimates that AE management during the treatment of HR+ advanced breast cancer will cost one-half to one-third less for EVE?+?EXE patients than for chemotherapy patients. The consideration of AE costs could have important implications in the context of healthcare spending for advanced breast cancer treatment.