C Ivanescu

Impact of enzalutamide on quality of life in men with metastatic castration-resistant prostate cancer after chemotherapy: additional analyses from the AFFIRM randomized clinical trial

The survival benefit of enzalutamide compared with placebo in men with progressive castration-resistant prostate cancer after prior docetaxel-based chemotherapy is accompanied by stabilization of patient HRQoL, as assessed by FACT-P. Application of different analytic methods to the FACT-P data further corroborate the HRQoL benefits observed with enzalutamide in the AFFIRM study.BACKGROUNDnTo present longitudinal changes in Functional Assessment of Cancer Therapy-Prostate (FACT-P) scores during 25-week treatment with enzalutamide or placebo in men with progressive metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy in the AFFIRM trial.nnnPATIENTS AND METHODSnPatients were randomly assigned to enzalutamide 160mg/day or placebo. FACT-P was completed before randomization, at weeks 13, 17, 21, and 25, and every 12 weeks thereafter while on study treatment. Longitudinal changes in FACT-P scores from baseline to 25 weeks were analyzed using a mixed effects model for repeated measures (MMRM), with a pattern mixture model (PMM) applied as secondary analysis to address non-ignorable missing data. Cumulative distribution function (CDF) plots were generated and different methodological approaches and models for handling missing data were applied. Due to the exploratory nature of the analyses, adjustments for multiple comparisons were not made. AFFIRM is registered with ClinicalTrials.gov, number NCT00974311.nnnRESULTSnThe intention-to-treat FACT-P population included 938 patients (enzalutamide, n = 674; placebo n = 264) with evaluable FACT-P assessments at baseline and ≥1 post-baseline assessment. After 25 weeks, the mean FACT-P total score decreased by 1.52 points with enzalutamide compared with 13.73 points with placebo (P < 0.001). In addition, significant treatment differences at week 25 favoring enzalutamide were evident for all FACT-P subscales and indices, whether analyzed by MMRM or PMM. CDF plots revealed differences favoring enzalutamide compared with placebo across the full range of possible response levels for FACT-P total and all disease- and symptom-specific subscales/indices.nnnCONCLUSIONnIn men with progressive mCRPC after docetaxel-based chemotherapy, enzalutamide is superior to placebo in health-related quality-of-life outcomes, regardless of analysis model or threshold selected for meaningful response.nnnCLINICAL TRIAL NUMBERnNCT00974311.

Skeletal-related events significantly impact health-related quality of life in metastatic castration-resistant prostate cancer: data from PREVAIL and AFFIRM trials

Background:We investigated the impact of skeletal-related events (SREs) on health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) in phase III trials of enzalutamide versus placebo.Methods:Patients with mCRPC experiencing at least one SRE during AFFIRM and PREVAIL were assessed for trajectory-adjusted mean change in HRQoL by first SRE using Functional Assessment of Cancer Therapy-Prostate (FACT-P; AFFIRM, three domains, and PREVAIL, nine domains) and EQ-5D (PREVAIL) instruments.Results:First SREs caused HRQoL deterioration in both trials. Spinal cord compression had the largest impact, with clinically meaningful reductions in seven of nine FACT-P domains in PREVAIL and all three in AFFIRM (mean (95% confidence interval (CI)) change in FACT-P total score –16.95 (–26.47, –7.44) and –9.69 (–16.10, –3.27), respectively). In PREVAIL, first SREs caused clinically meaningful declines in EQ-5D utility index, irrespective of category; spinal cord compression had the largest impact (mean (95% CI) change –0.24 (–0.39, –0.08)). In AFFIRM, FACT-P and FACT-General total scores showed clinically meaningful declines after radiation/surgery to bone.Conclusions:SREs were associated with clinically meaningful functional declines in the daily lives of patients with mCRPC. Spinal cord compression had the largest impact on HRQoL.

A Systematic Literature Review of The Economic Implications of Acute Bacterial Skin And Skin Structure Infections (Absssis).

Objectives: During the years, acute bacterial skin and skin structure infections (ABSSSIs) have seen an increase in incidence in many parts of the western world. Additionally, the treatment of ABSSSIs, generally consisting of surgical debridement or drainage and empiric antibiotics in the hospital, can be further complicated by emerging multi drug resistant bacteria, most notably methicillin-resistant Staphylococcus aureus (MRSA). As the incidence rates increase alongside with rising antibiotic resistance, ABSSSIs are becoming a significant burden for healthcare systems. This study aims to collect evidence on the healthcare resource utilization of ABSSSI and the economic implications of different treatment modalities for the management of these diseases. Methods: A systematic literature search in MEDLINE, Cochane and ISPOR abstract databases with predefined inclusion criteria and subsequent quality assessment was performed. Results: The search identified 1,799 unique publications of which 26 contained relevant economic data on ABSSSIs treatment and were therefore included in this manuscript. There were six healthcare resource utilization studies, 11 cost analyses, three cost-minimization and six cost-effectiveness analyses, of which only a single study reported quality adjusted life years. Vancomycin was evaluated in most studies (21), followed by linezolid (15), daptomycin (8) and others (7). Conclusions: This review provides an in-depth overview of the economic implications of current ABSSSI management. Major cost drivers of ABSSSI treatment were length of hospital stay and the overall cost associated with frequent intravenous antibiotics administration. While most studies (20) applied a hospital perspective, there was a substantial disparity on the specific costs in- or excluded in the analysis, and on the unit prices. This led to significant variations of the final cost outcomes. Notably, over 10-fold differences were found. The overall quality and comparability of the literature reviewed was sub-optimal, elevating the need for more high-quality and reproducible economic evaluations in the area of ABSSSIs.

Mapping Fact-P To EQ-5D In Metastatic Castration-Resistant Prostate Cancer (MCRPC): Performance Of A Previously Developed Algorithm When Applied On A Sample With A Different Disease Stage

Cristina Ivanescu,1 Louise Longworth,2 Konstantina Skaltsa,3 De Phung,4 Stefan Holmstrom4 1Quintiles, Hoofddorp, The Netherlands; 2Health Economics Research Group, Brunel University London, Uxbridge, UK; 3Quintiles, and Department of Public Health, Faculty of Medicine, University of Barcelona, Barcelona, Spain; 4Astellas Pharma Global Development, Leiden, The Netherlands Poster PRM138 ISPOR-EU 17th Annual Congress | Amsterdam, The Netherlands | 8–12 November 2014