Elsevier

European Journal of Cancer

Volume 116, July 2019, Pages 137-147
European Journal of Cancer

Original Research
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

https://doi.org/10.1016/j.ejca.2019.05.008Get rights and content
Under a Creative Commons license
open access

Highlights

  • Nivolumab + ipilimumab improved patient-reported outcomes versus chemotherapy in non–small-cell lung cancer.

  • Improvements were seen in lung cancer symptoms and in general health status.

  • Improvements with nivolumab + ipilimumab were rapid and durable.

  • Disease-related symptom deterioration was delayed with nivolumab + ipilimumab.

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 ∼90% 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.

Keywords

Antineoplastic agents
Carcinoma
Ipilimumab
Lung neoplasms
Nivolumab
Non–small-cell lung cancer
Platinum-doublet chemotherapy
Quality of life
Surveys and questionnaires

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