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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: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: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.

Project description:To evaluate the impact of adalimumab on health-related quality of life (HRQOL) for patients with moderate to severe plaque psoriasis.Psoriasis is a chronic, inflammatory, immune-mediated disease that has a significant impact on patients' HRQOL. Adalimumab is a fully human monoclonal antibody that blocks tumor necrosis factor, a pro-inflammatory cytokine, and is effective and well-tolerated for patients with moderate to severe psoriasis.Data were obtained for a secondary analysis of patients in a randomized, controlled Phase III trial evaluating the effect of adalimumab in patients with psoriasis (N = 1,205). Patients with moderate to severe psoriasis were randomized in a 2:1 ratio to adalimumab 80 mg (two 40 mg injections administered subcutaneously at baseline followed by one 40 mg injection every other week from Week 1 to Week 15) or placebo. Short Form-36 (SF-36) Health Survey scores of psoriasis patients were used to assess HRQOL and were compared with United States (US) population norms at baseline and Week 16.Baseline Physical Component Summary (PCS) scores for the placebo and adalimumab groups were similar to the general US population. Baseline mean Mental Component Summary (MCS) scores were significantly lower for the adalimumab and placebo groups compared with the general population (47.4, 47.7, and 50.8 points, respectively; p < 0.0001). PCS scores at Week 16 for patients receiving adalimumab had improved and were significantly greater than scores for the general US population (52.7 vs 48.9; p < 0.001). Compared with the general US population, MCS scores at Week 16 were similar for patients receiving adalimumab (51.2 vs 50.8; p = 1.000) and lower for patients receiving placebo (50.8 vs 48.7; p < 0.0001).Psoriasis has a broad impact on patient functioning and well-being. Improvement in skin lesions and joint symptoms associated with adalimumab treatment was accompanied by improvements in HRQOL to levels that were similar to or greater than those of the general US population.Clinicaltrials.gov NCT00237887.

Project description:BACKGROUND:Epithelial ovarian cancer (OC) remains a significant cause of morbidity and mortality for women worldwide. Patients may experience a multitude of disease- and treatment-related symptoms that can impact quality of life (QOL) and should be measured and reported in clinical trials. This systematic review investigated the adequacy of reporting of QOL in randomized phase III trials in OC in both the first-line and recurrent disease setting. MATERIALS AND METHODS:A systematic review of MEDLINE and EMBASE identified randomized clinical trials of systemic therapy in OC from 1980 to 2014. The adequacy of reporting QOL was evaluated with respect to adherence to established guidelines on reporting QOL in clinical trials and the recent recommendations on the inclusion of patient-reported outcomes in clinical trials from the Fifth Ovarian Cancer Consensus Conference. RESULTS:Of 3,247 abstracts, 35 studies, including 24,664 patients, met inclusion criteria. Twenty-two trials (63%) were in the first-line setting, with 13 (37%) in the recurrent setting. The inclusion of QOL assessments increased from 2% (1980s) to 62% (2010+). Quality of life was a co-primary endpoint in only one trial.Minimal clinically important differences in QOL were defined in eight trials (23%), with results included in the abstract in 37% and article in 86%. Compliance was reported in 26 trials (74%), with 13 trials (37%) reporting specifically how they dealt with missing data. Only seven trials reported the reasons for missing data (20%).Group results were published in 29 trials (83%), with 6 (17%) reporting individual patient results. Results were more commonly reported as a mean overall score (21 trials; 60%), with specific domain scores in only 9 trials (26%). No studies reported QOL beyond progression or included predefined context-specific endpoints based on objectives of treatment (i.e., palliation/cure/maintenance) and the patient population. Duration of benefit of palliative chemotherapy was reported in only one study. CONCLUSION:Inclusion and reporting of QOL as a trial endpoint has improved in phase III trials in OC, but there are still significant shortfalls that need to be addressed in future trials. IMPLICATIONS FOR PRACTICE:The impact of treatment on quality of life (QOL) is an important consideration in patients with ovarian cancer for whom treatment is often given with palliative intent. Both the disease and treatment impact a patient's QOL and require careful evaluation in clinical trials. Matching the QOL questions to the patient population of interest is critical. Similar rigor to that used to assess progression-based endpoints is essential to guide clinical decisions. This systematic review demonstrated that although the inclusion and reporting of QOL as a trial endpoint has improved in phase III trials there are still significant shortfalls that need to be addressed in future trials.

Dataset Information

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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