Demographics, treatment patterns, safety, and real-world effectiveness in patients aged 70 years and over with chronic lymphocytic leukemia receiving bendamustine with or without rituximab: a retrospective study.

OBJECTIVES: Bendamustine is a unique cytotoxic agent active against various human malignancies, including chronic lymphocytic leukemia (CLL). In vitro studies suggest that cytotoxic activity of bendamustine on CLL-derived cells is synergized by rituximab. A retrospective chart review was conducted to characterize treatment-naïve outpatients and those with relapsed disease aged 70 years and over with CLL receiving bendamustine (with or without rituximab) and to evaluate real-world patterns of care, safety, and effectiveness. METHODS: Using McKesson Specialty Care/US Oncology Network iKnowMed databases, 91 outpatients with at least two recorded visits and at least two cycles of bendamustine monotherapy or bendamustine-rituximab combination therapy were identified and included. Mean age at diagnosis and start of first therapy was 70.3 and 77.4 years respectively, and 63.7% of patients were men. RESULTS: Observed overall response rate was 56.3% in pooled treatment-naïve patients [n = 9; complete response (CR) 18.8%; partial response (PR) 37.5%; nodular partial response (nPR) 0%] and 58.7% in pooled patients with relapsed disease (n = 44; CR 13.3%; PR 44.0%; nPR 1.3%). Median time to progressive disease has not been reached for the 16 treatment-naïve patients (median follow up 15.1 months), and was 18.4 months for those with relapsed disease (n = 73). No unexpected toxicities were observed. Overall rate of blood/bone marrow toxicities (all grades) was 40.7%; grade 3/4 rates were 18.8% in treatment-naïve patients and 25.3% in those with relapsed disease. Most frequent nonhematologic adverse events were fatigue and rash. CONCLUSION: In this retrospective chart review of 91 outpatients with CLL aged 70 years and over, bendamustine (with or without rituximab) was an effective therapeutic option with manageable toxicity.

Utilization Patterns of IV Iron and Erythropoiesis Stimulating Agents in Anemic Chronic Kidney Disease Patients: A Multihospital Study.

Intravenous (IV) iron and Erythropoiesis Stimulating Agents (ESAs) are recommended for anemia management in chronic kidney disease (CKD). This retrospective cohort study analyzed utilization patterns of IV iron and ESA in patients over 18 years of age admitted to University Health System Hospitals with a primary or secondary diagnosis of CKD between January 1, 2006 to December 31, 2008. A clustered binomial logistic regression using the GEE methodology was used to identify predictors of IV iron utilization. Only 8% (n = 6678) of CKD patients on ESA therapy received IV iron supplementation in university hospitals. Those receiving iron used significantly less amounts of ESAs. Patient demographics (age, race, primary payer), patient clinical conditions (admission status, severity of illness, dialysis status), and physician specialty were identified as predictors of IV iron use in CKD patients. Use of IV iron with ESAs was low despite recommendations from consensus guidelines. The low treatment rate of IV iron represents a gap in treatment practices and signals an opportunity for healthcare improvement in CKD anemic patients.

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 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.

Media coverage of off-label promotion: a content analysis of US newspapers.

BACKGROUND: Promotion of drugs for off-label use is newsworthy, because it is an illegal but all too common strategy used by pharmaceutical companies. The print media are an important source of information about coverage of off-label promotion of drugs and devices and can influence public perceptions of the practice. OBJECTIVES: Print media coverage of off-label promotion during the years 1990-2008 were described and quantified. The primary themes and general tones relating to off-label promotion articles were evaluated. General concerns associated with off-label promotion and complaints about specific brand name drugs were also identified. METHODS: Content analyses of the top 6 US newspapers were conducted over the period of 1990-2008 to analyze the media coverage given to off-label promotion of drugs and devices. Headlines and full text of articles were analyzed for primary themes and tones of the coverage. Intercoder reliability tests were performed on all the study variables. RESULTS: One hundred and one articles were identified meeting the study inclusion criteria. Coverage varied by newspaper. The Wall Street Journal had the most coverage on the topic (45%), and USA Today and Chicago Tribune had the least coverage (5%). Overall, most of the stories sampled were deemed to have a negative tone in coverage (77%), focusing mainly on lawsuits against drug companies for promoting their drugs for off-label uses. Pfizer's Neurontin(®) (Pfizer Inc., New York, NY 10017, USA) and Johnson & Johnson's Retin-A(®) (Orthoneutrogena, Los Angeles, CA 90045, USA) received the most media attention. CONCLUSION: The news media helps shape public understanding of promotional practices of pharmaceutical companies and their potential benefits and harms. This study suggests that print media coverage is generally negative about off-label promotion, focusing on legal actions taken against drug companies and the negative consequences of such promotional practices.