Document Type

Journal Article

Publication Title

European Journal of Cancer Care

ISSN

1879-0852

Volume

116

First Page

137

Last Page

147

PubMed ID

31195357

Publisher

Elsevier Ltd

School

Exercise Medicine Research Institute

Comments

Originally published as: Reck, M., Schenker, M., Lee, K. H., Provencio, M., Nishio, M., Lesniewski-Kmak, K., ... Brahmer, J. (2019). 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. European Journal of Cancer, 116, 137-147. Original publication available here

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.

DOI

10.1016/j.ejca.2019.05.008

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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