Kristina Chen

Angiogenesis inhibitor therapies for metastatic renal cell carcinoma: effectiveness, safety and treatment patterns in clinical practice-based on medical chart review

Study Type – Symptom prevalence (case series)
Level of Evidence 4

Safety and treatment patterns of multikinase inhibitors in patients with metastatic renal cell carcinoma at a tertiary oncology center in Italy

BackgroundMultikinase inhibitors (MKIs) sunitinib and sorafenib have become a standard of care for metastatic renal cell carcinoma (mRCC). This study assessed safety and treatment patterns for these agents in a real-world clinical practice setting in Italy.MethodsA retrospective medical record review was performed at a tertiary oncology center in Italy. The study included MKI-naïve non-trial patients ≥18 years old, with a histological diagnosis of mRCC, and who received sunitinib or sorafenib as first MKI during 9/2005-7/2008. Data were collected on adverse events (AEs), treatment modifications (discontinuations, interruptions, dose changes), and reasons for these modifications.Results145 patients were included; 85 received sunitinib and 60 received sorafenib as first-line MKI. Median treatment duration was 6.6 (sunitinib) and 5.8 (sorafenib) months. 97.6% and 70.0% of patients receiving sunitinib and sorafenib, respectively, experienced ≥1 AE; 27.1% and 31.7% had ≥1 grade 3/4 AE. The most common any grade AE for sunitinib was fatigue/asthenia (81.2%), followed by mucositis/stomatitis (58.8%) and decreased taste sensation (42.4%), while for sorafenib this was fatigue/asthenia (43.3%) followed by hand-foot syndrome (38.3%) and diarrhea (31.7%). Treatment discontinuation, interruption, and dose reduction due to AEs occurred in 11.8%, 23.5%, and 30.6%, respectively, of patients receiving sunitinib, and 5.0%, 23.3%, and 36.7%, respectively, of patients receiving sorafenib.ConclusionsIn this retrospective study, most patients experienced ≥1 AE during first-line MKI treatment. AEs were reported frequently and resulted in treatment modifications in 40% of patients receiving sunitinib and 45% of patients receiving sorafenib. These results suggest a need for additional effective and more tolerable treatments for mRCC.

The Cost-Effectiveness of Initial Treatment of Multiple Myeloma in the U.S. With Bortezomib Plus Melphalan and Prednisone Versus Thalidomide Plus Melphalan and Prednisone or Lenalidomide Plus Melphalan and Prednisone With Continuous Lenalidomide Maintenance Treatment

The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP. Using a Markov model developed from a U.S. payers perspective, we compared VMP with MPT and MPR-R over a lifetime horizon. MPT and MPR-R were chosen because, like VMP, they are superior to MP in response and outcomes. Data from the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA; VMP), Intergroupe Francophone du Myelome (IFM) 99-06 (MPT), and MM-015 (MPR-R) trials were used. The IFM 99-06 study was selected because of the superior activity in this study compared with other MPT studies. Using patient-level (VMP) and published (MPT, MPR-R) data, we estimated the health-state transition and adverse event probabilities for each regimen, related costs, and state-specific utility estimates. Costs (in 2010 U.S. dollars) and health outcomes were discounted at 3%. Discounted lifetime direct medical costs were lowest with VMP at

Good Research Practices for Measuring Drug Costs in Cost-Effectiveness Analyses: A Managed Care Perspective: The ISPOR Drug Cost Task Force Report—Part III

119,102. MPT cost

Predictors of response to sequential sunitinib and the impact of prior VEGF-targeted drug washout in patients with metastatic clear-cell renal cell carcinoma

142,452 whereas MPR-R cost

Erratum to: Cost Effectiveness of Guanfacine Extended-Release versus Atomoxetine for the Treatment of Attention-Deficit/ Hyperactivity Disorder

248,358. Incremental cost-effectiveness ratio calculations projected that VMP would confer cost savings and better health outcomes relative to MPT and MPR-R. We conclude that VMP is highly likely to be cost-effective compared with MP, MPT, and MPR-R.

Cost Effectiveness of Guanfacine Extended-Release versus Atomoxetine for the Treatment of Attention-Deficit/Hyperactivity Disorder: Application of a Matching-Adjusted Indirect Comparison

OBJECTIVES The objective of this report is to provide guidance and recommendations on how drug costs should be measured for cost-effectiveness analyses conducted from the perspective of a managed care organization (MCO). METHODS The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (DCTF) was appointed by the ISPOR Board of Directors. Members were experienced developers or users of CEA models. The DCTF met to develop core assumptions and an outline before preparing a draft report. They solicited comments on drafts from external reviewers and from the ISPOR membership at ISPOR meetings and via the ISPOR Web site. RESULTS The cost of a drug to an MCO equals the amount it pays to the dispenser for the drugs ingredient cost and dispensing fee minus the patient copay and any rebates paid by the drugs manufacturer. The amount that an MCO reimburses for each of these components can differ substantially across a number of factors that include type of drug (single vs. multisource), dispensing site (retail vs. mail order), and site of administration (self-administered vs. physicians office). Accurately estimating the value of cost components is difficult because they are determined by proprietary and confidential contracts. CONCLUSION Estimates of drug cost from the MCO perspective should include amounts paid for medication ingredients and dispensing fees, and net out copays, rebates, and other drug price reductions. Because of the evolving nature of drug pricing, ISPOR should publish a Web site where current DCTF costing recommendations are updated as new information becomes available.

Achieving glycemic goal with initial versus sequential combination therapy using metformin and pioglitazone in type 2 diabetes mellitus.

OBJECTIVE To identify factors that can be used to identify metastatic clear cell RCC patients more likely to benefit from sequential sunitinib. PATIENTS AND METHODS We identified patients who failed sorafenib or bevacizumab and subsequently received sunitinib. We looked at objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) to sunitinib in relation to baseline clinical variables. RESULTS Seventy-one patients received sunitinib sequential therapy. Median duration of follow-up after starting sunitinib was 9.3 months. Median PFS was 5.8 months; median OS was not reached. Significantly higher ORR was seen in patients with normal hemoglobin (25.6%) [defined as >12 gm/dl for female; >13 gm/dl for male]. In addition, a shorter PFS for patients with low hemoglobin, and patients with time from diagnosis to first treatment ≤ 1 year was found. There was a shorter OS for patients ≥ 60 years old, with brain metastasis, low hemoglobin, and time from diagnosis to treatment ≤ 1 year. There was no difference in ORR, PFS, or OS in patients who started sunitinib after or within a 30-day period. CONCLUSIONS Metastatic clear-cell RCC patients with anemia have less clinical benefit from sequential sunitinib after failure of bevacizumab or sorafenib. Other factors associated with poor outcome include brain metastases, older age, and <1 year between diagnosis and first treatment. Importantly, no difference in outcomes was observed if sequential therapy was initiated within or after 30 days. External validation and prospective evaluation are needed to confirm these findings.

Access to diagnosis, treatment, and supportive services among pharmacotherapy-treated children/adolescents with ADHD in Europe: data from the Caregiver Perspective on Pediatric ADHD survey

Background: About 7% of children and adolescents are diagnosed with attention-deficit/hyperactivity disorder (ADHD) in the US. Patients with ADHD who are intolerant of or do not have an optimal response to stimulants often use non-stimulants as alternative therapies. Guanfacine extendedrelease (GXR) and atomoxetine (ATX) are the only non-stimulants approved by the US Food and Drug Administration for once-daily use in the treatment of children and adolescents with ADHD in the US. ATX has been on the market since 2002 while GXR was recently approved in 2009. To date, there is no comparative effectiveness or cost-effectiveness study comparing the two drugs.

Factors associated with caregiver burden among pharmacotherapy-treated children/adolescents with ADHD in the Caregiver Perspective on Pediatric ADHD survey in Europe

BACKGROUND About 7% of children and adolescents are diagnosed with attention-deficit/hyperactivity disorder (ADHD) in the US. Patients with ADHD who are intolerant of or do not have an optimal response to stimulants often use non-stimulants as alternative therapies. Guanfacine extended-release (GXR) and atomoxetine (ATX) are the only non-stimulants approved by the US Food and Drug Administration for once-daily use in the treatment of children and adolescents with ADHD in the US. ATX has been on the market since 2002 while GXR was recently approved in 2009. To date, there is no comparative effectiveness or cost-effectiveness study comparing the two drugs. OBJECTIVES The aim of this study was to assess the cost effectiveness of GXR versus ATX for the treatment of ADHD in children and adolescents, using the comparative efficacy results from a matching-adjusted indirect comparison (MAIC). METHODS The MAIC method was used to compare the efficacy between GXR (target dose and lower doses) and ATX (target dose) in the absence of head-to-head clinical trials. Individual patients in the GXR trials were weighted such that the summary baseline characteristics and the efficacy of the placebo arm of the GXR trials matched exactly with those from published ATX trials. After weighting, the efficacy (i.e. change in the ADHD rating scale, fourth edition [ADHD-RS-IV] total score from baseline) was compared between each GXR dosing group and the ATX group. The results from the MAIC analyses were used to populate a 1-year Markov model that is used to compare the cost effectiveness of GXR versus ATX from a US third-party payer perspective. Effectiveness outcomes for each treatment group were estimated as the proportion of responders, defined as patients with ≥25% reduction in ADHD-RS-IV total score from baseline, and average quality-adjusted life years (QALYs). Utilities associated with response/non-response and disutilities due to adverse events were applied in the model. Costs included drug and medical service costs and were inflated to 2011 US dollars (