Assessment of zoledronic acid treatment patterns and clinical outcomes in patients with bone metastases from genitourinary cancers

Abstract

Background:

Patients with bone metastases secondary to genitourinary (GU) cancer are at risk for skeletal-related events (SREs), including bone pain requiring palliative radiotherapy, fractures or surgery to bone, spinal cord compression, and hypercalcemia of malignancy. These SREs can be debilitating and potentially life-limiting. This study examined treatment practices and the association of treatment patterns with Zometa (zoledronic acid, ZOL), an intravenous bisphosphonate (IV-BP), with SREs and fractures. (Zometa is a registered trademark of Novartis Pharmaceuticals Corporation, USA.)

Methods:

Retrospective analysis of commercial and Medicare Advantage enrollment and medical claims data was performed to evaluate IV-BP use and SRE patterns in adult patients with GU cancers. Criteria included diagnosis of ≥1 bone metastasis and prostate cancer (PC), renal cell carcinoma (RCC), or bladder cancer (BlC) between January 2001 and December 2006; continuous healthcare plan enrollment for ≥6 months before the index date; and no evidence of prior IV-BP use. Patients were followed until disenrollment from the healthcare plan or December 2007.

Results:

Of 6347 patients (PC, n?=?4976; RCC, n?=?941; BlC, n?=?430; mean [standard deviation] age: 68.9 [11.1] years), only ～23% received ZOL. The mean time between diagnosis of bone metastasis and ZOL initiation was ～108 days. Among patients with PC, fracture risk was significantly smaller for ZOL vs no IV-BP (incidence rate ratio?=?0.70; p?<?0.001), and 2-year survival was significantly longer for ZOL-treated vs no IV-BP patients (p?=?0.007). Patients with longer persistency on ZOL had a smaller fracture risk than patients with shorter persistency. Sub-set analyses were not performed for RCC and BIC because the proportion of patients treated was too low.

Limitations:

Interpretation of this claims-based analysis must be tempered by the inherent limitations of observational data, such as limited and accurate available information, and unavailable information including clinical or disease-specific parameters.

Conclusions:

Intravenous BP therapy is not always received in patients with bone metastases secondary to GU cancers, and, when used, there are typically long time periods before treatment initiation. Without IV-BPs, PC patients have significantly larger risks of fracture and death compared with ZOL-treated patients, and benefits appear to be larger with increasing persistency on ZOL.     

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.     

Healthcare costs,treatment patterns,and resource utilization among pancreatic cancer patients in a managed care population

Abstract

Background:

Pancreatic adenocarcinoma has few effective treatment options and poor survival. The objective of this study was to characterize treatment patterns and estimate the costs and resource use associated with its treatment in a commercially-insured US population.

Methods:

In this retrospective claims-based analysis, individuals ≥18 years old with evidence of pancreatic adenocarcinoma between January 1, 2001 and December 31, 2010 were selected from a managed care database. Treatment phase (either initial non-metastatic or metastatic) was determined using a claims-based algorithm. Patients in the pancreatic cancer population were matched 1:3 to a control population. Resource use (events/person-years), treatment patterns, and healthcare costs (per-patient per-month, PPPM) were determined during a variable length follow-up period (from first pancreatic cancer diagnosis to earliest of death, disenrollment, or study end).

Results:

In this study, 5262 pancreatic cancer patients were matched to 15,786 controls. Rates of office visits, inpatient visits, ER visits, and inpatient stays, and mean total all-cause healthcare costs PPPM ($15,480 vs $1001) were significantly higher among cancer patients than controls (all p?<?0.001). Mean inpatient costs were the single largest cost driver ($9917 PPPM). Also, mean total all-cause healthcare costs were significantly higher during the metastatic treatment phase vs the initial treatment phase of non-metastatic disease ($21,637 vs $10,358, p?<?0.001).

Conclusions:

These results indicate that pancreatic cancer imposes a substantial burden on the US healthcare system, and that treatment of more advanced disease is significantly more costly than initial treatment of non-metastatic disease.

Limitations:

Additional research is needed to validate the accuracy of the claims-based algorithms used to identify the treatment phase.     

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.     

An economic comparison of the net clinical benefit and treatment costs of raltitrexed and 5-fluorouracil + leucovorin (Mayo regimen) in advanced colorectal cancer

Summary

Background

This paper describes an economic evaluation in which raltitrexed (Tomudex®) was compared with 5-fluorouracil (5-FU) + leucovorin (LV), and where net clinical benefits were related to differential health service costs. Raltitrexed, a specific inhibitor of thymidylate synthetase, has shown anticancer activity against a range of solid tumours.

Tomudex® is a registered trademark ofZeneca Pharmaceuticals

Materials and Methods

In a large, open, randomised, multicentre study in patients with advanced colorectal cancer, raltitrexed (n = 223) and 5-FU plus LV (n = 216) showed similar efficacy in terms of patient survival and objective response (i.e. tumour shrinkage rates). Palliative benefits were seen in both groups of patients and suggest that patients with stable disease are as likely to show improvement as those with a tumour response. Reductions compared with 5-FU plus LV in the number of toxicity days (median 1.5 vs 8 treatment days) and administration days (6 vs 22 days) with raltitrexed were consistent with a net clinical benefit.

Results

A cost minimisation analysis that drew on data from a number of sources showed direct medical costs per month to be similar for the two treatments (£781 for raltitrexed vs £834 for 5-FU + LV).

Conclusions

Raltitrexed therefore represents a clinically effective alternative to 5-FU plus LV (Mayo regimen) and offers net clinical benefit to patients with advanced colorectal cancer at no apparent additional cost.     

Cost drivers for breast,lung, and colorectal cancer care in a commercially insured population over a 6-month episode: an economic analysis from a health plan perspective

Aims: In the absence of clinical data, accurate identification of cost drivers is needed for economic comparison in an alternate payment model. From a health plan perspective using claims data in a commercial population, the objective was to identify and quantify the effects of cost drivers in economic models of breast, lung, and colorectal cancer costs over a 6-month episode following initial chemotherapy.

Research design and methods: This study analyzed claims data from 9,748 Cigna beneficiaries with diagnosis of breast, lung, and colorectal cancer following initial chemotherapy from January 1, 2014 to December 31, 2015. We used multivariable regression models to quantify the impact of key factors on cost during the initial 6-month cancer care episode.

Results: Metastasis, facility provider affiliation, episode risk group (ERG) risk score, and radiation were cost drivers for all three types of cancer (breast, lung, and colorectal). In addition, younger age (p?p?p?p?p?Conclusions: Value-based reimbursement models in oncology should appropriately account for key cost drivers. Although claims-based methodologies may be further augmented with clinical data, this study recommends adjusting for the factors identified in these models to predict costs in breast, lung, and colorectal cancers.     

Antiepileptic drug treatment patterns and economic burden of commercially-insured patients with refractory epilepsy with partial onset seizures in the United States

Abstract

Objective:

To assess the economic burden in direct healthcare utilization and costs for refractory epileptic patients with partial onset seizures (POS) and assess the antiepileptic drug (AED) treatment patterns among these patients.     

Clinical comorbidities,treatment patterns,and direct medical costs of patients with osteoarthritis in usual care: a retrospective claims database analysis

Abstract

Objective:

Comorbidities and resource utilization among patients with osteoarthritis (OA) in clinical practice have been infrequently characterized. The purpose of this study was to examine comorbidities, pain-related pharmacotherapy, and direct medical costs of patients with OA in clinical practice.

Method:

This retrospective cohort analysis used medical and pharmacy claims data from the LifeLink? Database. OA patients (ICD-9-CM codes 715.XX) were matched (age, gender, and region) with individuals without OA. Comorbidities, pain-related pharmacotherapy, and direct medical costs (pharmacy, outpatient, inpatient, total) were examined for the calendar year 2008.

Results:

The sample consisted of 112,951 OA patients and 112,951 controls (mean age: 56.9 [SD?=?9.5] years; 62% female). Relative to controls, OA patients were significantly more likely (p?<?0.0001) to have comorbidities, including musculoskeletal (84.3 vs. 37.1%) and neuropathic pain (22.0 vs. 6.1%) conditions, depression (12.4 vs. 6.4%), anxiety (6.6 vs. 3.5%), and sleep disorders (11.9 vs. 4.2%). OA patients were significantly more likely (p?<?0.0001) to receive pain-related medications, including opioids (40.7 vs. 17.1%), NSAIDs (37.1 vs. 11.5%), tramadol (9.8 vs. 1.8%), and adjunctive medications for treating depression, anxiety, and insomnia. Mean [SD] total direct medical costs were more than two times higher among OA patients ($12,905 [$21,884] vs. $5099 [$13,855]; p?<?0.001) and median costs were more than three times higher ($6188 vs. $1879; p?<?0.0001). Study limitations include potential errors in coding and recording; overestimation of the comorbidity burden; inability to link condition of interest, OA, with prescribed medications; and possible underestimation of the true costs of OA, because indirect costs were not considered and the direct costs were from a third party payer (commercial insurance) perspective.

Conclusion:

The patient burden of OA was characterized by a high prevalence of comorbidities. The payer burden was also substantial, with significantly greater use of pain-related and adjunctive medications, and higher direct medical costs.