Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial.
Eur J Cancer
; 116: 137-147, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31195357
ABSTRACT
BACKGROUND:
In the phase III CheckMate 227 study, first-line nivolumab + ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; ≥10 mutations/megabase).AIM:
To evaluate patient-reported outcomes (PROs) in this population.METHODS:
Disease-related symptoms and general health status were assessed using the validated PRO questionnaires Lung Cancer Symptom Scale (LCSS) and EQ-5D, respectively. LCSS average symptom burden index (ASBI) and three-item global index (3-IGI) and EQ-5D visual analogue scale (VAS) and utility index (UI) scores and changes from baseline were analysed descriptively. Longitudinal changes were assessed by mixed-effect model repeated measures (MMRMs) and time to first deterioration/improvement analyses.RESULTS:
In the high TMB population, PRO questionnaire completion rates were â¼90% at baseline and >80% for most on-treatment assessments. During treatment, mean changes from baseline with nivolumab + ipilimumab showed early, clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; with chemotherapy, symptoms and health-related quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following induction (EQ-5D VAS). MMRM-assessed changes in symptom burden were improved with nivolumab + ipilimumab versus chemotherapy. Symptom deterioration by week 12 was lower with nivolumab + ipilimumab versus chemotherapy (22.3% versus 35.0%; absolute risk reduction 12.7% [95% confidence interval 2.4-22.5]), irrespective of discontinuation. Time to first deterioration was delayed with nivolumab + ipilimumab versus chemotherapy across LCSS and EQ-5D summary measures.CONCLUSION:
First-line nivolumab + ipilimumab demonstrated early, sustained improvements in PROs versus chemotherapy in patients with advanced NSCLC and high TMB. CLINICAL TRIAL REGISTRATION NCT02477826.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
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Medidas de Resultados Relatados pelo Paciente
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Antineoplásicos Imunológicos
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Neoplasias Pulmonares
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Cancer
Ano de publicação:
2019
Tipo de documento:
Article