Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2019 Jul:116:137-147.
doi: 10.1016/j.ejca.2019.05.008. Epub 2019 Jun 11.

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

Martin Reck  1 , Michael Schenker  2 , Ki Hyeong Lee  3 , Mariano Provencio  4 , Makoto Nishio  5 , Krzysztof Lesniewski-Kmak  6 , Randeep Sangha  7 , Samreen Ahmed  8 , Judith Raimbourg  9 , Kynan Feeney  10 , Romain Corre  11 , Fabio Andre Franke  12 , Eduardo Richardet  13 , John R Penrod  14 , Yong Yuan  15 , Faith E Nathan  16 , Prabhu Bhagavatheeswaran  17 , Michael DeRosa  18 , Fiona Taylor  19 , Rachael Lawrance  20 , Julie Brahmer  21
Affiliations
Free article
Clinical Trial

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

Martin Reck et al. Eur J Cancer. 2019 Jul.
Free article

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.

PubMed Disclaimer

Publication types

Associated data