S. Holmstrom

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.

Health economics and outcomes research within drug development: challenges and opportunities for reimbursement and market access within biopharma research.

Healthcare decision makers who determine funding for new medical technologies depend on manufacturers to provide evidence of the technologys efficacy, safety and cost-effectiveness. Constrained budgets and increasing reliance on formal health technology assessment (HTA) have created an abundance of external hurdles that manufacturers must navigate to ensure successful product commercialization. These demands have pushed pharmaceutical companies to adjust their internal structures to coordinate generation of appropriate evidence. In this article we summarize internal and external opportunities for manufacturers to establish a foundation of evidence for successful market access, starting in Phase I of development and continuing throughout the post-approval product lifecycle.

Are treatment benefits in neuropathic pain reflected in the self assessment of treatment questionnaire

Background/objectiveThe Self Assessment of Treatment (SAT) questionnaire was developed to reflect key patient reported outcomes of Neuropathic Pain (NP) treatments. This study aimed to understand how patients perceived the relevance and ease of understanding of the questions in the SAT and to recommend modifications based on patient and clinician interviews.MethodsSemi-structured interviews were conducted with clinicians and NP patients to provide information regarding treatment attributes and the impact of pain. Patients were debriefed on the SAT, a 5-item scale evaluating pain, activity level, quality of life (QoL) and satisfaction with treatment (recommend treatment and undergo treatment again). The SAT has a recall period reflecting back to the start of treatment. The qualitative analysis software ATLAS.ti 5.0 was used to analyze patient transcripts. Changes to the SAT were integrated into the questionnaire for a second round of debriefing interviews.ResultsThree NP clinicians and 44 patients (20 painful diabetic neuropathy, 16 HIV-associated neuropathy and 8 post herpetic neuralgia) with a mean age of 60.3 (12.3) years and an even gender distribution were interviewed. Patient treatment experience included anticonvulsants (73%), antidepressants (34%), opioids (25%), and topical medications (41%). Pain descriptors and treatment attributes were similar across the three NP groups. Pain relief was judged the most important treatment attribute, followed by ability to undertake activities. Sleep improvement was another important attribute. Activity limitations and QOL were perceived as too broad and non-specific, and were split into 3 concepts each (activity limitations was split into self care, daily and physical activities and QOL was split into sleep, emotions, and social function). A 7-day recall period was introduced. The item stem and response options were made consistent, and a baseline and follow-up questionnaires were developed (except for the satisfaction items) to enable monitoring onset of treatment benefit and change over time.ConclusionsThe content validity of the revised SAT was improved by the qualitative research, and NP treatment benefits are reflected in a more consistent fashion by the changes. Baseline and follow-up versions make it possible to perform assessments of change over time.

Validation of the Self-Assessment of Treatment Questionnaire among Patients with Postherpetic Neuralgia

Introduction. A five-item Self-Assessment of Treatment (SAT) was developed to assess improvement and satisfaction with treatment associated with the application of a novel high concentration 8% capsaicin topical patch in clinical trials in patients with postherpetic neuralgia (PHN). This study evaluated the item performance and psychometric properties of the SAT. Methods. The SAT, Brief Pain Inventory, SF-36v2, Short-Form McGill Pain Questionnaire, and Patient and Clinician Global Impression of Change (PGIC; CGIC) scores were measured in two 12-week Phase 3 clinical trials. Factor analysis assessed the underlying factor structure, followed by examination of the reliability and validity of the multi-item domain. Results. Pooled data from 698 patients completing SAT after 12 weeks of treatment were analyzed. A one-factor model combining three of the five items emerged as the optimal solution. Internal consistency reliability of this treatment efficacy factor was high (Cronbachs alpha = 0.89). Construct validity was demonstrated by moderate to high correlations with change in other study endpoints. SAT mean scores consistently discriminated between patient change groups defined by PGIC and CGIC. Conclusions. The measurement properties of the three-item version of SAT are valid and reliable for assessment of treatment with a high concentration capsaicin patch among patients with PHN.

762PDIMPACT OF ENZALUTAMIDE ON SKELETAL RELATED EVENTS (SRES), PAIN AND QUALITY OF LIFE (QOL) IN THE PREVAIL TRIAL

ABSTRACT Aim: Enzalutamide (ENZ) improved overall survival vs. placebo (PL) in PREVAIL, a phase 3 trial in asymptomatic/mildly symptomatic chemotherapy-naive patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) [Beer et al, ASCO GU 2014]. PREVAIL also prospectively evaluated SREs, pain and QoL. Methods: Pts were randomized to ENZ (160mg/day; n = 872) or PL (n = 845). SREs were assessed throughout the study and time to 1st SRE measured. QoL was assessed at baseline (BL) and during treatment (tx) on the FACT-P and EQ-5D; changes from BL over time were compared using repeated measures analyses. Pain was assessed with the BPI-SF at BL, and months (mo) 3 and 6. Pts with BL and ≥1 post-BL score were analyzed using pre-specified criteria for clinically meaningful pain progression (pain severity: increase ≥30% from BL; pain interference: increase ≥50% of BL standard deviation) and QoL deterioration (Cella et al, VIH 2009; Pickard et al, HQOL 2007). Results: Median tx duration was 16.6 (ENZ) and 4.6 (PL) mo; BL pain and QoL scores were similar between arms. Overall, 32% (ENZ) and 37% (PL) of pts reported at least one SRE. Compared to PL, ENZ significantly reduces the risk of 1st SRE occurrence (hazard ratio: 0.72 [0.61, 0.84], p Time to 1st deterioration (mo), median (95% Cl) ENZ (n = 872) PL (n = 845) P-value Hazard ratioa (95% CI) EQ-5D instrument Visual analogue scale 22.14 (19.35;27.66) 13.83 (11.07;16.59) 0.67 (0.56;0.80) FACT-P instrument Physical well-being 10.84 (8.31;11.07) 5.55 (5.49;5.62) 0.74 (0.65;0.85) Functional well-being 8.54 (8.31;11.07) 3.09 (2.86;5.55) 0.72 (0.62;0.82) Emotional well-being 19.48 (16.59;25.07) 11.01 (8.25;11.40) 0.67 (0.57;0.79) Social well-being 24.87 (14.16;NYR) 8.51 (6.01;13.86) 0.74 (0.63;0.86) Prostate Cancer Subscale 5.65 (5.55;8.31) 2.83 (2.79;2.96) 0.69 (0.60;0.78) FACT-P total score 11.30 (11.07;13.86) 5.55 (5.49;5.59) 0.62 (0.54;0.72) Pain progression, n(%) Pain severity 329/802 (41) 317/628 (50) Pain interference 247/788 (31) 255/613 (42) Conclusions: In PREVAIL, in addition to overall survival benefit, ENZ was also associated with clinically significant patient benefits compared to PL, including a delay in time to 1st SRE, superior QoL, a delay in QoL deterioration, and significantly lower proportion of pts with pain. Disclosure: Y. Loriot: Consultant/Advisory: Astellas Research Funding: Astellas Other: Sanofi, Janssen, Bayer, Cellgene; K. Miller: Consulting: Astellas/Medivation Consultancy: Astellas, Amgen, Janssen, Medivation, Novartis, Roche Lectures: Novartis, Janssen, Pierre-Fabre; C.N. Sternberg: Honoraria: Astellas, Johnson & Johnson, Ipsen, Bayer, Millenium; K. Fizazi: Advisory Board: Astellas/Medivation Speaker: Astellas/Medivation; J.S. de Bono: Astellas/Medivation; S. Chowdhury: Advisory Board/Lecture: Astellas, Janssen, Sanofi-Aventis, Dendreon Speaker: GSK; C. Higano: Research funding: Astellas/Medivation, Algeta, Aragon, Dendreon, Sanofi Consultant/Advisory: Astellas/Medivation, Dendreon, Bayer, Johnson & Johnson; S. Noonberg: Employee: Medivation; S. Holmstrom, F.G. Perabo and D. Phung: Employee: Astellas; H. Mansbach: Employee: Medivation; C. Ivanescu: Astellas: payment for writing or reviewing a manuscript, provision of writing assistance or administrative support, consultancy; K. Skaltsa: Astellas: Payment for writing or reviewing a manuscript, provision of writing assistance or administrative support, consultancy; T. Beer: Research Funding: Astellas/Medivation, Janssen Consultant: Janssen; B. Tombal: Advisor: Astellas/Medivation, Ferring Speaker: Astellas, Ferring

Payer/Hta Requirements In Metastatic Breast Cancer

INTRODUCTION • Triple-negative breast cancer (TNBC) represents 10%–20% of invasive breast cancers1 and has a very poor prognosis.2 There is a particular unmet need in TNBC, with a lack of clinically established targeted therapies3; chemotherapy is the only option for metastatic TNBC.4 • To facilitate access to new treatments, it is increasingly important to understand payer evidence needs in addition to regulatory evidence requirements.5 • Traditionally, payers focus on hard endpoints such as overall survival (OS), and recommendations for reimbursement would ideally be supported by statistically significant improvement in OS. However, this is sometimes difficult due to long follow-up durations and post-study treatment.

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