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Health-related quality of life results from the phase III CheckMate 067 study.

ABSTRACT: BACKGROUND:Nivolumab, a monoclonal antibody of immune checkpoint programmed death 1 on T cells (PD-1), combined with ipilimumab, an immune checkpoint cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, as combination therapy on the one hand and nivolumab as monotherapy on the other, have both demonstrated improved efficacy compared with ipilimumab alone in the CheckMate 067 study. However, the combination resulted in a higher frequency of grade 3/4 adverse events (AEs), which could result in diminished health-related quality of life (HRQoL). Here we report analyses of HRQoL for patients with advanced melanoma in clinical trial CheckMate 067. PATIENTS AND METHODS:HRQoL was assessed at weeks 1 and 5 per 6-week cycle for the first 6 months, once every 6 weeks thereafter, and at two follow-up visits using the European Organization for Research and Treatment of Care Core Quality of Life Questionnaire and the EuroQoL Five Dimensions Questionnaire. In addition to the randomised population, patient subgroups, including BRAF mutation status, partial or complete response, treatment-related AEs of grade 3/4, and those who discontinued due to any reason and due to an AE, were investigated. RESULTS:Nivolumab and ipilimumab combination and nivolumab alone both maintained HRQoL, and no clinically meaningful deterioration was observed over time compared with ipilimumab. In addition, similar results were observed across patient subgroups, and no clinically meaningful changes in HRQoL were observed during follow-up visits for patients who discontinued due to any cause. CONCLUSION:These results further support the clinical benefit of nivolumab monotherapy and nivolumab and ipilimumab combination therapy in patients with advanced melanoma. The finding that the difference in grade 3/4 AEs between the arms did not translate into clinically meaningful differences in the reported HRQoL may be relevant in the clinical setting. STUDY NUMBER:NCT01844505.

SUBMITTER: Schadendorf D

PROVIDER: S-EPMC5737813 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Health-related quality of life results from the phase III CheckMate 067 study.

Schadendorf Dirk D Larkin James J Wolchok Jedd J Hodi F Stephen FS Chiarion-Sileni Vanna V Gonzalez Rene R Rutkowski Piotr P Grob Jean-Jacques JJ Cowey C Lance CL Lao Christopher C Wagstaff John J Callahan Margaret K MK Postow Michael A MA Smylie Michael M Ferrucci Pier Francesco PF Dummer Reinhard R Hill Andrew A Taylor Fiona F Sabater Javier J Walker Dana D Kotapati Srividya S Abernethy Amy A Long Georgina V GV

European journal of cancer (Oxford, England : 1990) 20170623

<h4>Background</h4>Nivolumab, a monoclonal antibody of immune checkpoint programmed death 1 on T cells (PD-1), combined with ipilimumab, an immune checkpoint cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, as combination therapy on the one hand and nivolumab as monotherapy on the other, have both demonstrated improved efficacy compared with ipilimumab alone in the CheckMate 067 study. However, the combination resulted in a higher frequency of grade 3/4 adverse events (AEs), which ...[more]

PMID: 28651159

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Project description:BackgroundNivolumab has shown significant survival benefit and a favorable safety profile compared with dacarbazine chemotherapy among treatment-naïve patients with metastatic melanoma in the CheckMate 066 phase III study. Results from the health-related quality of life (HRQoL) analyses from CheckMate 066 are presented.Patients and methodsHRQoL was evaluated at baseline and every 6 weeks while on treatment using the European Organisation for Research and Treatment of Care (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire (EQ-5D). Via a multi-step statistical plan, data were analyzed descriptively, cross-sectionally, and longitudinally, adjusting for baseline covariates, in patients having baseline plus ?1 post-baseline assessment.ResultsBaseline-adjusted completion rates for all HRQoL questionnaires across treatment arms were 65% and 70% for dacarbazine and nivolumab, respectively, and remained similar throughout treatment. The mean baseline HRQoL scores were similar for patients treated with nivolumab and dacarbazine. Baseline HRQoL levels with nivolumab were maintained over time. This exploratory analysis showed a between-arm difference in favor of nivolumab on the EQ-5D utility index and clinically meaningful EQ-5D improvements from baseline at several time points for patients receiving nivolumab. Patients treated with nivolumab did not show increased symptom burden as assessed by the EORTC QLQ-C30. No HRQoL change was noted with dacarbazine patients up to week 43, although the high attrition rate after week 13 did not allow any meaningful analyses. Patients receiving nivolumab deteriorated significantly later than those receiving dacarbazine on several EORTC QLQ-C30 scales and the EQ-5D utility index.ConclusionsIn addition to prolonged survival, these exploratory HRQoL results show that nivolumab maintains baseline HRQoL levels to provide long-term quality of survival benefit, compared with dacarbazine in patients with advanced melanoma.

Project description:BackgroundThe programmed death-1 (PD-1) inhibitor nivolumab prolongs disease-free survival in patients with muscle-invasive urothelial carcinoma (MIUC).ObjectiveTo evaluate the effects of nivolumab on health-related quality of life (HRQoL) after radical resection in patients with MIUC.Design, setting, and participantsWe used data from 709 patients in CheckMate 274 (NCT02632409; 282 with programmed death ligand 1 [PD-L1] expression ≥1%), an ongoing randomized, double-blind, placebo-controlled phase 3 trial of adjuvant nivolumab.InterventionIntravenous injection of nivolumab (240 mg) or placebo every 2 wk for ≤1 yr.Outcome measurements and statistical analysisHRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EQ-5D-3L. Linear mixed-effect models for repeated measures were used to compare nivolumab and placebo on changes in HRQoL. Time to confirmed deterioration (TTCD) of HRQoL was analyzed by Cox proportional hazards regression.Results and limitationsIn the full HRQoL evaluable population, no clinically meaningful deterioration of HRQoL was observed in either treatment arm. Moreover, nivolumab was noninferior to placebo on changes from baseline for all main outcomes. The median TTCD for fatigue was 41.0 wk for nivolumab and 44.3 wk for placebo (hazard ratio [HR]: 1.11, 95% confidence interval [CI], 0.89-1.39). For the visual analog scale, the median TTCD was not reached for nivolumab and it was 57.6 wk for placebo (HR: 0.78, 95% CI, 0.61-1.00). The median TTCD for the other main outcomes was not reached in either treatment arm. The findings were similar for patients with PD-L1 expression ≥1%.ConclusionsThese results demonstrate that nivolumab did not compromise the HRQoL of patients with MIUC in CheckMate 274.Patient summaryNivolumab is being researched as a new treatment for patients with bladder cancer (urothelial carcinoma). We found that nivolumab maintained quality of life while increasing the time until cancer returns in patients whose bladder cancer had spread or grown and who had unsuccessfully tried platinum-containing chemotherapy.

Project description:BackgroundImpact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1β cytokine trap) to treat RP.MethodsQualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n = 16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n = 9). All participants received rilonacept weekly during a 6-week base treatment period (TP) plus an optional 18-week extension period (EP). Tapering of concomitant medications, including corticosteroids (CS), was permitted during EP. HRQoL was assessed using the PROMIS GH, and patient-reported pain and blood levels of c-reactive protein (CRP) were collected at Baseline and follow-up periods. A secondary, descriptive analysis of the Phase 2 trial efficacy results was completed using HRQoL measures to characterize both the impact of RP and the treatment effect of rilonacept.ResultsInformation from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline (mean PROMIS Global Physical Health [GPH] and Global Mental Health [GMH], were lower than population norm average). In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved during EP, during CS tapering or discontinuation, without disease recurrence (low pain scores and CRP levels continued during the TP and EP).ConclusionThis is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to CS.Trial registrationClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522 .

Project description:BACKGROUND:Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2?years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2?years among patients with PsA in the FUTURE 2 study. METHODS:PASDAS (cut-off scores: remission ??1.9; LDA >?1.9 and?<?3.2; Moderate Disease Activity ??3.2 and?<?5.4; and high disease activity [HDA]???5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150?mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures. RESULTS:In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300?mg and in 15.2% and 19.2%, respectively, in the secukinumab 150?mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission?+?LDA at week 16 with secukinumab 300 and 150?mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2?years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2?years. CONCLUSIONS:Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2?years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01752634 . Registered on December 19, 2012. EUDRACT, 2012-004439-22 . Registered on December 12, 2012.

Project description:Abstract Introduction Omidubicel, an advanced cell therapy used for allogeneic hematopoietic stem cell transplant has demonstrated faster hematopoietic recovery, shorter hospitalization, and lower rates of bacterial, viral, and invasive fungal infections compared with umbilical cord blood (UCB) in a phase III randomized trial (NCT02730299;Blood 2021;138:1429). Objective The objective was to compare changes in health-related quality of life (HRQL) between treatment groups in the phase III trial. Methods Patients who received protocol-defined treatment and provided HRQL evaluations at baseline and ≥1 follow-up visit were analyzed. Outcomes included Functional Assessment of Cancer Therapy General (FACT-G) domain scores for physical, social/family, functional and emotional well-being, and EQ-5D-3L index scores, at days 42, 100, 180, and 365 post-transplant. HRQL changes from baseline were compared using mixed effect models with repeated measures, adjusting for age, sex, race, region, primary diagnosis, HCT comorbidity index, and baseline HRQL score. Average HRQL over time was compared using the area under the curve (AUC) of mean HRQL trajectories in each treatment group. Results Seventy-five patients (omidubiceln = 37, UCB n = 38) provided HRQL data for inclusion and were representative of the full randomized population (N = 125) at baseline. Median age was 38 years, and 41% were female. During the first year post-transplant, patients receiving omidubicel had numerically superior average FACT-G domain and EQ-5D-3L index scores compared with UCB, with mean differences across time points ranging from 1.4 to 3.1 for physical well-being, 0 to 1.3 for social/family well-being, 0.5 to 1.4 for emotional well-being, 1.6 to 3.2 for functional well-being, and 0.03 to 0.09 for the EQ-5D-3L index score. Minimal clinically important differences (MCIDs) were exceeded at ≥1 time point for mean physical and functional well-being (MCIDs = 2 units) and for the EQ-5D-3L (MCID = 0.07 units). Initial mean declines in HRQL occurred for all measures at day 42 and were consistently numerically smaller in the omidubicel group than in the UCB group. Averaging across the first year post-transplant, patients receiving omidubicel had significantly improved HRQL for physical and functional well-being domains (P < .05 for comparison of AUCs). Discussion Along with faster time to engraftment, lower infection risk, and shorter hospitalization, omidubicel was associated with meaningfully greater preservation or improvement of important HRQL domains compared with UCB.

Project description:BackgroundWe examined treatment-seeking overweight and obese youths to better understand the gender, age, and treatment modality differences in generic and disease-specific health-related quality of life (HRQOL).MethodsThis multicenter study included 1,916 patients (mean = 12.6 years; 57% females; mean zBMI = 2.4) who started treatment for overweight and obesity in 48 treatment facilities between July 2005 and October 2006. The facilities offered either inpatient treatment or outpatient programs. Prior to treatment, all participants completed the generic KIDSCREEN-27 HRQOL-questionnaire, the self-perception subscale of the generic KIDSCREEN-52 and the disease-specific obesity module of the KINDLR.The patients' HRQOL was compared to the KIDSCREEN reference sample from the general population by one-way analyses of variance, adjusting for age, gender, and socioeconomic status. Independent t-tests were conducted to compare disease-specific HRQOL scores between patients by gender and age group. Significant mean differences in HRQOL between inpatients and outpatients were explored by one-way analyses of variance, adjusting for age, gender, and zBMI. Effect sizes 'd' were calculated employing the estimated marginal means and the pooled standard deviation (m(treatment) - m(norm)/SD(pooled)).ResultsThe patients' HRQOL scores were impaired relative to German norms, with effect sizes up to d = 1.12. The pattern of impairment was similar in boys and girls as well as in children and adolescents. In each of the analyses, at least three of six KIDSCREEN subscales were affected. Regardless of gender and age group, the highest impairments were found in self-perception and physical well-being. Because of the strong decrease in HRQOL in the general population during adolescence, compared to age-specific norms, adolescents were less impaired than were children. However, overweight and obese adolescents (especially females) reported the lowest absolute HRQOL scores. HRQOL varied with the intensity of treatment. Inpatients had significantly lower scores than did outpatients, even after adjusting for age, gender and zBMI.ConclusionsThe results suggest the presence of differences in HRQOL with regard to gender, age, and treatment modality in treatment-seeking overweight and obese youths. Research and clinical practice must consider the particular impairments of inpatients as well as the impairments of (especially female) adolescents.

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Health-related quality of life results from the phase III CheckMate 067 study.

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Health-related quality of life results from the phase III CheckMate 067 study.

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