Stacie Hudgens

Quality of life in patients with newly diagnosed chronic phase chronic myeloid leukemia on imatinib versus interferon alfa plus low-dose cytarabine: results from the IRIS Study.

PURPOSE Quality of life (QOL) outcomes in patients with chronic myeloid leukemia (CML) were evaluated in an international phase III study. PATIENTS AND METHODS Newly diagnosed patients with chronic phase CML were randomly assigned to imatinib or interferon alfa plus subcutaneous low-dose cytarabine (IFN+LDAC). Cross-over to the other treatment was permitted because of intolerance or lack of efficacy. Patients completed cancer-specific QOL (Functional Assessment of Cancer Therapy-Biologic Response Modifiers) and utility (Euro QoL-5D) questionnaires at baseline and during treatment (n = 1,049). The primary QOL end point was the Trial Outcome Index (TOI; a measure of physical function and well-being). Secondary end points included social and family well-being (SFWB), emotional well-being (EWB), and the utility score. Primary analyses were intention to treat with secondary analyses accounting for cross-over. RESULTS Patients receiving IFN+LDAC experienced a large decline in the TOI, whereas those receiving imatinib maintained their baseline level. Treatment differences at each visit were significant (P <.001) and clinically relevant in favor of imatinib. Mean SFWB, EWB, and utility scores were also significantly better for those patients taking imatinib. Patients who crossed over to imatinib experienced a large increase in TOI; significant (P <.001) differences were observed between patients who did and did not cross over in favor of imatinib. CONCLUSION Imatinib offers clear QOL advantages compared with IFN+LDAC as first-line treatment of chronic phase CML. In addition, patients who cross over to imatinib from IFN+LDAC experience a significant improvement in QOL compared with patients who continue to take IFN+LDAC.

Atherosclerotic risk factor reduction in peripheral arterial disease: Results of a national physician survey

OBJECTIVE: Individuals with peripheral arterial disease (PAD) have a 3- to 6-fold increased risk of coronary heart disease and stroke compared to those without PAD. We documented physician-reported practice behavior, knowledge, and attitudes regarding atherosclerotic risk factor reduction in patients with PAD.DESIGN: National physician survey.PATIENTS/PARTICIPANTS: General internists (N=406), family practitioners (N=435), cardiologists (N=473), and vascular surgeons (N=264) randomly identified using the American Medical Association’s physician database.MEASUREMENTS AND MAIN RESULTS: Physicians were randomized to 1 of 3 questionnaires describing a) a 55- to 65-year-old patient with PAD; b) a 55- to 65-year-old patient with coronary artery disease (CAD), or c) a 55- to 65-year-old patient without clinically evident atherosclerosis (no disease). A mailed questionnaire was used to compare physician behavior, knowledge, and attitude regarding risk factor reduction for each patient. Rates of prescribed antiplatelet therapy were significantly lower for the patient with PAD than for the patient with CAD. Average low-density lipoprotein levels at which physicians “almost always” initiated lipid-lowering drugs were 121.6±23.5 mg/dL, 136.3±28.9 mg/dL, and 149.7±24.4 mg/dL for the CAD, PAD, and no-disease patients, respectively (P<.001). Physicians stated that antiplatelet therapy (P<.001) and cholesterol-lowering therapy (P<.001) were extremely important significantly more often for the CAD than for the PAD patient. Perceived importance of risk factor interventions was highly correlated with practice behavior. Compared to other specialties, cardiologists had lowest thresholds, whereas vascular surgeons had the highest thresholds for initiating cholesterol-lowering interventions for the patient with PAD. Cardiologists were significantly more likely to report “almost always” prescribing antiplatelet therapy for the patient with PAD than were all other physicians.CONCLUSIONS: Deficiencies in physician knowledge and attitudes contribute to lower rates of atherosclerotic risk factor reduction for patients with PAD. Reversing these deficiencies may reduce the high rates of cardiovascular morbidity and mortality associated with PAD.

Cross-Cultural Evaluation of Health Status Using Item Response Theory FACT-B Comparisons Between Austrian and U.S. Patients With Breast Cancer

To make meaningful cross-cultural comparisons of health-related quality of life (HRQOL) or to pool international research data, it is essential to create culturally unbiased measures that detect clinically important differences between patients. We evaluated the measurement properties of the Functional Assessment of Cancer Therapy-Breast (FACT-B) in 111 Austrian and 144 U.S. patients with breast cancer using item response theory (IRT) methods. A small number of items were identified as displaying statistically significant differential item functioning (DIF), suggesting possible measurement bias. The majority of the items functioned similarly between the two cultural groups. U.S. patients reported lower (worse) physical function and well-being compared with Austrian patients, higher (better) social/family well-being and similar emotional well-being, before and after adjustment for DIF. IRT and related measurement models provide useful methods for assessing cross-cultural equivalence and determining which items can be pooled across languages before analyzing HRQOL data. Determination of clinically significant cross-cultural differences will require additional investigation.

Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial

BACKGROUND Cutaneous T-cell lymphomas are rare non-Hodgkin lymphomas with substantial morbidity and mortality in advanced disease stages. We compared the efficacy of mogamulizumab, a novel monoclonal antibody directed against C-C chemokine receptor 4, with vorinostat in patients with previously treated cutaneous T-cell lymphoma. METHODS In this open-label, international, phase 3, randomised controlled trial, we recruited patients with relapsed or refractory mycosis fungoides or Sézary syndrome at 61 medical centres in the USA, Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the UK, Japan, and Australia. Eligible patients were aged at least 18 years (in Japan, ≥20 years), had failed (for progression or toxicity as assessed by the principal investigator) at least one previous systemic therapy, and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate haematological, hepatic, and renal function. Patients were randomly assigned (1:1) using an interactive voice web response system to mogamulizumab (1·0 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or vorinostat (400 mg daily). Stratification was by cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB-II vs III-IV). Since this study was open label, patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival by investigator assessment in the intention-to-treat population. Patients who received one or more doses of study drug were included in the safety analyses. This study is ongoing, and enrolment is complete. This trial was registered with ClinicalTrials.gov, number NCT01728805. FINDINGS Between Dec 12, 2012, and Jan 29, 2016, 372 eligible patients were randomly assigned to receive mogamulizumab (n=186) or vorinostat (n=186), comprising the intention-to-treat population. Two patients randomly assigned to mogamulizumab withdrew consent before receiving study treatment; thus, 370 patients were included in the safety population. Mogamulizumab therapy resulted in superior investigator-assessed progression-free survival compared with vorinostat therapy (median 7·7 months [95% CI 5·7-10·3] in the mogamulizumab group vs 3·1 months [2·9-4·1] in the vorinostat group; hazard ratio 0·53, 95% CI 0·41-0·69; stratified log-rank p<0·0001). Grade 3-4 adverse events of any cause were reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group. The most common serious adverse events of any cause were pyrexia in eight (4%) patients and cellulitis in five (3%) patients in the mogamulizumab group; and cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the vorinostat group. Two (67%) of three on-treatment deaths with mogamulizumab (due to sepsis and polymyositis) and three (33%) of nine on-treatment deaths with vorinostat (two due to pulmonary embolism and one due to bronchopneumonia) were considered treatment-related. INTERPRETATION Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma. FUNDING Kyowa Kirin.

Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial

BACKGROUND In the SPARTAN trial, addition of apalutamide to androgen deprivation therapy, as compared with placebo plus androgen deprivation therapy, significantly improved metastasis-free survival in men with non-metastatic castration-resistant prostate cancer who were at high risk for development of metastases. We aimed to investigate the effects of apalutamide versus placebo added to androgen deprivation therapy on health-related quality of life (HRQOL). METHODS SPARTAN is a multicentre, international, randomised, phase 3 trial. Participants were aged 18 years or older, with non-metastatic castration-resistant prostate cancer, a prostate-specific antigen doubling time of 10 months or less, and a prostate-specific antigen concentration of 2 ng/mL or more in serum. Patients were randomly assigned (2:1) to 240 mg oral apalutamide per day plus androgen deprivation therapy, or matched oral placebo plus androgen deprivation therapy, using an interactive voice randomisation system. Permuted block randomisation was used according to the three baseline stratification factors: prostate-specific antigen doubling time (>6 months vs ≤6 months), use of bone-sparing drugs (yes vs no), and presence of local-regional nodal disease (N0 vs N1). Each treatment cycle was 28 days. The primary endpoint was metastasis-free survival. The trial was unblinded in July, 2017. In this prespecified exploratory analysis we assessed HRQOL using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-3L questionnaires, which we collected at baseline, day 1 of cycle 1 (before dose), day 1 of treatment cycles 1-6, day 1 of every two cycles from cycles 7 to 13, and day 1 of every four cycles thereafter. This study is registered with ClinicalTrials.gov, number NCT01946204. FINDINGS Between Oct 14, 2013, and Dec 15, 2016, we randomly assigned 1207 patients to receive apalutamide (n=806) or placebo (n=401). The clinical cutoff date, as for the primary analysis, was May 19, 2017. Median follow-up for overall survival was 20·3 months (IQR 14·8-26·6). FACT-P total and subscale scores were associated with a preservation of HRQOL from baseline to cycle 29 in the apalutamide group; there were similar results for EQ-5D-3L. At baseline, the mean for FACT-P total score in both the apalutamide and placebo groups were consistent with the FACT-P general population norm for US adult men. Group mean patient-reported outcome scores over time show that HRQOL was maintained from baseline after initiation of apalutamide treatment and was similar over time among patients receiving apalutamide versus placebo. Least-squares mean change from baseline shows that HRQOL deterioration was more apparent in the placebo group. INTERPRETATION In asymptomatic men with high-risk non-metastatic castration-resistant prostate cancer, HRQOL was maintained after initiation of apalutamide treatment. Considered with findings from SPARTAN, patients who received apalutamide had longer metastasis-free survival and longer time to symptomatic progression than did those who received placebo, while preserving HRQOL. FUNDING Janssen Research & Development.

Quality of Life in Cutaneous T-cell Lymphoma Patients Treated with the Anti-CCR4 Monoclonal Antibody Mogamulizumab versus Vorinostat: Results from MAVORIC

NHL-265 Quality of Life in Cutaneous T-cell Lymphoma Patients Treated with the Anti-CCR4 Monoclonal Antibody Mogamulizumab versus Vorinostat: Results from MAVORIC Auris Huen , Pierluigi Porcu, Stacie Hudgens, Pietro Quaglino, Richard Cowan, Lysbeth Floden, Athanasios Tsianakas, Mollie Leoni, Stephen Dale, Madeline Duvic MD Anderson Cancer Center, Houston, Texas, United States; Thomas Jefferson University, Philadelphia, Pennsylvania, United States; Clinical Outcomes Solutions, Tucson, Arizona, United States; University of Turin, Turin, Italy; Christie Hospital Foundation, Manchester, United Kingdom; Specialist Clinic Bad Bentheim, Bad Bentheim, Germany; Kyowa Kirin Pharmaceutical Development, Inc., Princeton, New Jersey, United States

Evaluation of Quality of Life at Progression in Patients with Soft Tissue Sarcoma

Introduction. Soft Tissue Sarcoma (STS) is a rare malignancy of mesodermal tissue, with international incidence estimates between 1.8 and 5 per 100,000 per year. Understanding quality of life (QoL) and the detrimental impact of disease progression is critical for long-term care and survival. Objectives. The primary objective was to explore the relationship between disease progression and health-related quality of life (HRQoL) using data from Eisais study (E7389-G000-309). Methods. This was a 1 : 1 randomized, open-label, multicenter, Phase 3 study comparing the efficacy and safety of eribulin versus dacarbazine in patients with advanced STS. The QoL analysis was conducted for the baseline and progression populations using the European Organization for Research and Treatment of Cancer 30-item core QoL questionnaire (EORTC QLQ-C30). Results. There were no statistical differences between the two treatment arms at baseline for any domain (p > 0.05; n = 452). Of the 399 patients who experienced disease progression (unadjusted and adjusting for histology), dacarbazine patients had significantly lower Global Health Status, Physical Functioning scores, and significantly worse Nausea and Vomiting, Insomnia, and Appetite Loss (p < 0.05). Conclusions. These results indicate differences in HRQoL overall and at progression between dacarbazine and eribulin patients, with increases in symptom severity observed among dacarbazine patients.

Measuring and understanding quality of survival in oncology.

e291 Background: Health status, burden of illness, and quality of life (QOL) are considered crucial for clinical decision making in cancer. More specifically, quality of survival (QOS) in patients with cancer must be paramount in treatment considerations from early stage disease to palliative care. Measuring QOL provides information beyond biomedical outcomes, offers a unique understanding from the patients perspective, and has demonstrated influence over study conclusions where differences in QOL are more often detected in studies comparing intervention to no intervention rather than comparative studies with systemic therapies. METHODS This panel presentation is focused on the crossfunctional perspectives of critical research areas for understanding QOS in oncology. As such, this presentation seeks to address the need for patient-focused research in oncology including: 1) the importance of the patients voice in early and metastatic disease, 2) what endpoints should we consider in oncology trials for understanding the impact on patients, 3) modeling time to patient reported decline as a critical endpoint in understanding survival, 4) quality of life as a story rather than a statistic, 5) understanding health states for response and progression. RESULTS The authors of this panel seek to present real world examples for each of the above topics as well as introduce methodologies for improving QOS value messaging in oncology. CONCLUSIONS In cancer studies, the primary response is measured as survival benefit with the ability to measure biomarkers such as tumor response, blood levels, etc. However, measureable endpoints in oncology from patient report contribute to the understanding of symptom improvement or decline (change over the course of treatment), change in function (e.g., physical functioning), side effects (treatment toxicity; e.g., patient reported potential with the PRO common terminology criteria for adverse events), economic aspects, interaction between biomarkers of progression or response and patient-reported symptoms, function, and QOL should be carefully estimated to fully understand treatment efficacy and safety, and inform patients of duration and cycle of toxicity onset; disease symptoms and changes.