Investigation of adverse-event-related costs for patients with metastatic breast cancer in a real-world setting.

BACKGROUND: Existing treatments for metastatic breast cancer (mBC) are often effective but can cause adverse events (AEs). This study aimed to identify AEs associated with chemotherapies commonly used in mBC treatment (phase 1) and to quantify the economic impact of these AEs (phase 2). MATERIALS AND METHODS: Patients in phase 1 had at least one claim for therapy for mBC, with at least one episode with single or multiple agents. The most common chemotherapy-related complications were identified using medical and pharmacy claims data. In phase 2, patients meeting study criteria were divided into four treatment cohorts by the line of treatment and chemotherapy received: first-line taxane-treated patients, second-line taxane-treated patients, first-line capecitabine-treated patients, and second-line capecitabine-treated patients. Average monthly AE-related health care costs per cohort were stratified by cost component. Total monthly costs per number of AEs were also calculated. RESULTS: On average, patients in phase 1 (n = 1,551) had 2 episodes of treatment, with a mean duration of 131 days. The most frequently noted complications were anemia (50.7% of mBC treatment episodes), bilirubin elevation (26.4%), and leukopenia (24.8%). In phase 2, costs related to AEs were primarily driven by incremental inpatient, outpatient, and pharmacy costs. Increases in average monthly costs ranged from $854 (9.0%) to $5,320 (69.5%), according to cohort. Overall costs increased with increasing numbers of AEs. CONCLUSION: Chemotherapy-related AEs in patients with mBC are associated with a substantial economic burden that increases with the number of AEs reported.

Comparison of actual hospital costs versus DRG revenues for in-patient treatment of febrile neutropenia during adjuvant anthracycline plus/minus taxane-based chemotherapy for primary breast cancer.

BACKGROUND: In flat-rate reimbursement systems, the hospital's own costs should not exceed its revenues. In a cohort of primary breast cancer (pBC) patients, costs and reimbursement for febrile neutropenia (FN) were compared to verify cost coverage. METHODS: A prospective, observational study in pBC patients receiving adjuvant anthracycline ± taxane-based chemotherapy calculated the costs per in-patient FN episode. The correlating revenues were retrospectively analyzed from diagnosis-related group (DRG) invoices. The actual costs of the therapies were compared to the individual DRG revenues, and the results are presented from the provider's perspective. RESULTS: In 50 patients, n = 11 patients were treated for FN as in-patients. The hospital's overall treatment costs were € 18,288, on average (Ø) € 1663 per case (range € 1139-2344); the overall DRG revenues were € 23,593, Ø € 2145 per case (range € 1266-2660). In n = 8 cases, the DRGs were cost covering, and in n = 3 cases, a loss was observed, but overall resulting in a gain of Ø € 482 per case and thus being cost covering for the provider. Inadequate DRG coding (n = 4/11; 36.4%) resulted in a preventable loss of Ø € 1069/case. CONCLUSIONS: The costs of FN treatment vary substantially and DRG reimbursements do not necessarily reflect the provider's costs. Surprisingly, the in-patient treatment of FN here is overall more than cost covering if adequately coded. The main reasons are asymmetrical costs for this FN low-risk pBC group. These results emphasize the importance of correct medical coding to avoid potential losses.

Costs of first-line doublet chemotherapy and lifetime medical care in advanced non-small-cell lung cancer in the United States.

OBJECTIVES: The purpose of this study was to identify total lifetime medical-care costs and costs associated with first-line chemotherapy treatment among older patients with stage IIIB/IV non-small-cell lung cancer treated with commonly used two-drug chemotherapy ("doublet") regimens in the United States. METHODS: Study patients included individuals aged 65 years and older who received a diagnosis of stage IIIB/IV non-small-cell lung cancer in a Surveillance, Epidemiology and End Results cancer registry between 1997 and 2002 and who received first-line treatment with commonly used doublet regimens. Patients were followed retrospectively in the Surveillance, Epidemiology and End Results-Medicare database to evaluate lifetime medical-care costs and costs while on first-line chemotherapy treatment. Pairwise comparisons of treatment costs were estimated by using nonparametric bootstrap methods. RESULTS: Lifetime medical-care costs totaled approximately $70,000 and on-treatment costs for first-line chemotherapy totaled approximately $30,000 among study patients and were dominated by hospitalization and physician costs. Lifetime costs were significantly higher among patients treated with first-line cisplatin/carboplatin (platinum) plus a taxane compared with those who received platinum plus gemcitabine [difference: $4781 ($1558-$8039)] or other doublet therapy [difference: $5961 ($2333-$9614)]. Total on-treatment costs for first-line chemotherapy were significantly higher among patients treated with platinum plus a taxane compared with those who received platinum plus gemcitabine [difference: $5825 ($3872-$7770)], platinum plus another agent [difference: $5968 ($3995-$7975)], or another doublet therapy [difference: $3663 ($1620-$5740)]. CONCLUSIONS: There is a cost differential between first-line doublet regimens in terms of lifetime and on-treatment costs. Although doublet therapy with platinum and a taxane was the most frequently utilized regimen, it was associated with the highest lifetime and on-treatment costs.

Real-world and trial-based cost-effectiveness analysis of bevacizumab in HER2-negative metastatic breast cancer patients: a study of the Southeast Netherlands Breast Cancer Consortium.

INTRODUCTION: The aim of our analysis was to assess the real-world cost-effectiveness of bevacizumab in addition to taxane treatment versus taxane monotherapy for HER2-negative metastatic breast cancer compared with the cost-effectiveness based on the efficacy results from a trial. METHODS: A state transition model was built to estimate costs, life years (LYs) and quality-adjusted life years (QALYs) for both treatments. Two scenarios were examined: a real-world scenario and a trial-based scenario in which transition probabilities were primarily based on a real-world cohort study and the E2100 trial, respectively. In both scenarios, costs and utility parameter estimates were extracted from the real-world cohort study. Moreover, the Dutch health care perspective was adopted. RESULTS: In both the real-world and trial scenarios, bevacizumab-taxane is more expensive (incremental costs of €56,213 and €52,750, respectively) and more effective (incremental QALYs of 0.362 and 0.189, respectively) than taxane monotherapy. In the real-world scenario, bevacizumab-taxane compared to taxane monotherapy led to an incremental cost-effectiveness ratio (ICER) of €155,261 per QALY gained. In the trial scenario, the ICER amounted to €278,711 per QALY gained. CONCLUSION: According to the Dutch informal threshold, bevacizumab in addition to taxane treatment was not considered cost-effective for HER2-negative metastatic breast cancer both in a real-world and in a trial scenario.

First-line bevacizumab plus taxane-based chemotherapy for metastatic breast cancer: cost-minimisation analysis.

AIM: To carry out a cost minimisation analysis including a comparison of the costs arising from first-line treatment by bevacizumab plus docetaxel (BD) versus bevacizumab plus paclitaxel (BP) of patients with metastatic breast cancer (mBC). PATIENT AND METHODS: All consecutive patients with human epidermal growth receptor 2-negative mBC and treated at Besançon University hospital between 2006 and 2010 by a first-line therapy containing bevacizumab plus taxane were retrospectively studied. Economic analysis took into account costs related to drugs, hospitalization and healthcare travel. RESULTS: Progression-free survival difference between the two treatments was insignificant (p-value=0.31). BP treatment was associated with a higher mean total cost than that of BD treatment, €53,093 ± 34,395 versus €60,196 ± 48,766, respectively. CONCLUSION: Whereas bevacizumab is recommended for first-line treatment of mBC with paclitaxel-based chemotherapy, our study has shown that BD treatment is the most cost-efficient regimen. It could be an attractive option in France, with a potential cost saving of €24,000,000 per year.

Bevacizumab in combination with a taxane for the first-line treatment of HER2-negative metastatic breast cancer.

This paper presents a summary of the evidence review group (ERG) report into the use of bevacizumab (Avastin®, Roche) in combination with a taxane for the treatment of untreated metastatic breast cancer (mBC). The main clinical effectiveness data were derived from a single, open-label randomised controlled trial (RCT) (E2100) that evaluated the addition of bevacizumab to weekly (q.w.) paclitaxel in patients with human epidermal growth factor receptor 2-negative mBC who had not previously received chemotherapy for advanced disease. This trial reported statistically significant increases in median progression-free survival (PFS) for the addition of bevacizumab (5.8-11.3 months). Median overall survival was not significantly different between the two groups; whether this is a true null finding or due to crossover between treatment arms cannot be established, as relevant data were not collected. The manufacturer reported that the addition of bevacizumab to paclitaxel q.w. therapy was associated with a significant improvement in quality of life, as measured by FACT-B (functional assessment of cancer therapy for breast cancer) scores. However, the ERG noted that these results were based on extreme imputed values, the removal of which led to non-significant differences in quality of life. The manufacturer conducted an indirect comparison. However, owing to methodological limitations and concerns about the validity and exchangeability of the included trials, the ERG did not consider the findings to be reliable. One additional relevant RCT [AVADO (Avastin and Docetaxel); BO17708] evaluating the addition of bevacizumab to docetaxel was excluded from the manufacturer's submission. This was summarised by the ERG. In terms of response rate and PFS, AVADO reported a markedly smaller benefit of adding bevacizumab to docetaxel than that reported for adding bevacizumab to q.w. paclitaxel in E2100. AVADO also reported no statistically significant effect of combination therapy versus docetaxel in terms of overall survival. The manufacturer developed a de novo economic model that considered patients with the same baseline characteristics as women in the E2100 trial. The model assessed BEV + PAC - bevacizumab 10 mg/kg every 2 weeks in combination with paclitaxel 90 mg/m2 weekly for 3 weeks followed by 1 week of rest; PAC q.w. - paclitaxel (monotherapy) 90 mg/m2 weekly for 3 weeks followed by 1 week of rest; DOC - docetaxel (monotherapy) 75 mg/m2 on day 1 every 21 days (considered current UK NHS clinical practice in the submission); and GEM + PAC - gemcitabine 1250 mg/m2 on days 1 and 8 plus paclitaxel 175 mg/m2 on day 1 every 21 days. Pairwise comparisons were made between BEV + PAC and PAC (using the E2100 trial), BEV + PAC and DOC, and BEV + PAC and GEM + PAC. Based on NHS list prices, the manufacturer's model estimated incremental cost-effectiveness ratios (ICERs) for BEV + PAC of £ 117,803, £ 115,059 and £ 105,777 per QALY gained, relative to PAC, DOC and GEM + PAC regimens, respectively. If the NHS Purchasing and Supply Agency prices for PAC with a 10-g cap on the cost per patient of BEV were used instead, the ICERs for BEV + PAC were estimated at £ 77,314, £ 57,753 and £ 60,101 per QALY, respectively. The submission suggested that the regimen of BEV + DOC is not cost-effective because it is considered less effective and more costly than BEV + PAC. Analysis by the ERG suggested that alternative assumptions can increase the ICERs further and, based on current prices, no plausible changes to the model assumptions will bring the ICERs for BEV + PAC lower.

Cost comparison of capecitabine in patients with breast cancer.

OBJECTIVE: Capecitabine may have a higher acquisition cost compared with other select chemotherapy agents; however, its use is not associated with many of the costs typically encountered with intravenous chemotherapy, such as costs incurred through administration procedures and the management of subsequent tolerability issues. This study compared the cost of capecitabine- and taxane-based regimens in the treatment of breast cancer. STUDY DESIGN: Thomson Reuters MarketScan, a US employer claims database, was used to identify patients with a breast cancer diagnosis between 2000 and 2005 and at least one chemotherapy claim or hormone treatment in 2004 or 2005. METHODS: Cost data for treatment administration and management of selected chemotherapy-related adverse events were collected. Multivariate analyses were performed to adjust for differences in patient demographic and clinical factors. RESULTS: A total of 3630 patients were included in this analysis; 4216 treatment episodes were recorded. Mean unadjusted total monthly expenditures were lowest for capecitabine regimens compared with taxane plus anthracycline or other taxane regimens ($8445 vs. $13,295 and $12,323, respectively; P < 0.0001). The adjusted total monthly cost for capecitabine regimens was lower than the cost for taxane plus anthracycline regimen ($10,895 vs. $13,115) and other taxane regimens ($9253 vs. $12,116). Adjusted complication costs for taxane treatment episodes were almost double than those seen with capecitabine ($5509 for anthracycline plus taxane vs. $2940, and $3829 for other taxane regimens vs. $1750). CONCLUSIONS: Lower complication-related expenditures with capecitabine therapy accounted for majority of the cost differential seen in comparison with taxane-based therapy.

A cost-effectiveness analysis of chemotherapy for patients with recurrent platinum-sensitive epithelial ovarian cancer.

OBJECTIVE: The majority of patients with advanced epithelial ovarian cancer (EOC) will experience a recurrence after primary chemotherapy and receive second-line chemotherapy. Patients who have a disease-free interval >6 months (platinum-sensitive) will often receive multiple chemotherapy regimens. Therefore, our goal was to assess the effectiveness and medical costs of chemotherapy for platinum-sensitive patients with advanced EOC. METHODS: A decision analysis model compared several chemotherapeutic strategies in a hypothetical cohort of 10,000 platinum-sensitive EOC patients with recurrent disease: (a) best supportive care (BSC); (b) second-line monotherapy; (c) second-line combination therapy; (d) third-line chemotherapy after disease progression on second-line monotherapy or combination therapy; (e) fourth-line chemotherapy after disease progression on second- and third-line chemotherapy. RESULTS: BSC and second-line therapies were cost-effective strategies. The cost-effectiveness ratios ranged from $2896 for second-line monotherapy to $4914 for fourth-line previous monotherapy. Compared to BSC, second-line monotherapy gained an additional 8 months of overall survival (OS) with a favorable incremental cost-effectiveness ratio (ICER) of $24,228 per life year saved (LYS). The ICER for second-line combination therapy compared to second-line monotherapy was also favorable ($46,068 per LYS). Although third- and fourth-line chemotherapy provided small improvements in OS, they were dominated by other strategies or had an unfavorable ICER (>$50,000 per LYS). CONCLUSIONS: Second-line chemotherapy is cost-effective for patients with platinum-sensitive recurrent EOC. Due to minimal improvements in overall survival, third- and fourth-line chemotherapy are not cost-effective strategies.

PHARMAC funding of 9-week concurrent trastuzumab (Herceptin) for HER2-positive early breast cancer.

A 9-week regimen of trastuzumab (Herceptin) given concurrently with a taxane will be funded for HER2-positive early breast cancer patients in New Zealand. The use of trastuzumab in this population has been investigated in sequential (after chemotherapy) or concurrent (with taxane chemotherapy) settings. Five RCTs have been reported--HERA, NSABP B31, NCCTG N9831, BCIRG 006, and FinHer. Uncertainty persists about optimal regimen duration, dose and sequencing, how to minimise cardiotoxicity, and long-term clinical outcomes. The evidence for the 9-week concurrent regimen was sufficient to justify funding. This regimen has shown results comparable to longer duration treatments; allows more patients to be treated; is relatively cost-effective; and DHBs have indicated they can provide sufficient ancillary support services. Longer duration regimens remain unfunded because of uncertainty surrounding long term clinical benefits and risks; the high cost; effects on DHB services; and their consequential unfavourable relative cost effectiveness. New data--from the sequential treatment arm of trial N9831, showing benefits that were small and statistically non-significant, and the HERA 23-month follow-up, suggesting a waning in efficacy with time--have since cast further doubt on the extent and durability of the sequential 12-month regimen's efficacy. DHBs and PHARMAC remain open to funding longer duration regimens if cost effectiveness improves significantly and budget/resource implications become acceptable. PHARMAC has committed to international efforts (the SOLD trial) to resolve questions of optimal treatment duration.

Implementation and results of a test dose program with taxanes.

PURPOSE: A pilot taxane test-dose policy was developed and implemented to determine whether the severity of patient hypersensitivity reaction and drug waste would be reduced. PATIENTS AND METHODS: Data from 206 eligible cancer patients undergoing first-dose taxane chemotherapy were analyzed. The severity of hypersensitivity reactions before and after the implementation of taxane test dose was graded (scale 1-4) and analyzed for statistical differences between groups. Average drug wastage was calculated before and after program initiation. RESULTS: Twenty-two of 206 patients (10.7%) experienced a hypersensitivity reaction. The mean hypersensitivity reaction severity for reacting patients who did not receive a test dose (N = 12) was 3.3, and for those who were given a test dose (N = 10), it was 1.5. Only one of five patients who experienced a hypersensitivity reaction that required hospitalization was from the test-dose group. The value of drug alone wasted before test-dose utilization was about $1794 per reacting patient, and the use of taxane test doses saved approximately $1784 per reacting individual. This represented more than a $178 savings for every patient receiving a taxane for the first time. These figures do not include resuscitation, hospital, and other subsequent other costs associated with morbidity. CONCLUSIONS: Implementation of a taxane test-dose policy significantly reduced hypersensitivity reaction severity, drug wastage, and hospitalizations.

Population-based pharmacoeconomic model for adopting capecitabine/docetaxel combination treatment for anthracycline-pretreated metastatic breast cancer.

PURPOSE: To model the cost-effectiveness of adopting capecitabine/docetaxel combination therapy in place of single-agent taxane therapy for women in the province of Ontario, Canada, receiving treatment for anthracycline-pretreated metastatic breast cancer. METHODS: Clinical effectiveness and economic data were combined in a population model, from the perspective of a universal health care system. Estimates of clinical effectiveness and medical resource utilization were derived prospectively during a phase III randomized controlled trial comparing single-agent docetaxel with capecitabine/docetaxel combination therapy. Population data were obtained from the Cancer Care Ontario Registry and provincial prescription claims data. RESULTS: During 1999-2000, 542 patients were eligible for taxane monotherapy. As capecitabine/docetaxel treatment confers a median 3-month survival benefit compared with docetaxel monotherapy, the projected survival gain in these patients was 136 life-years. The results of the cost-effectiveness analysis demonstrate that the survival benefit provided by the addition of capecitabine to single-agent docetaxel is afforded at a small incremental cost of Canadian $3,691 per life-year gained. Hospitalization costs for treatment of adverse events were less for patients receiving capecitabine/docetaxel combination therapy than for those receiving docetaxel monotherapy. The results were robust for adjustments in treatment costs and adverse effects costs. CONCLUSION: Due to its 3-month survival gain and small incremental treatment cost, capecitabine/docetaxel is judged to be a highly cost-effective treatment in anthracycline-pretreated advanced breast cancer. From the perspective of the Ontario health care system, the addition of capecitabine to docetaxel in this patient population is a clinically appropriate and economically acceptable treatment strategy.