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. 2019 Jul;116:137-147. doi: 10.1016/j.ejca.2019.05.008. Epub 2019 Jun 11.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Female
  • Health Status
  • Humans
  • Ipilimumab / administration & dosage
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Nivolumab / administration & dosage
  • Patient Reported Outcome Measures*
  • Quality of Life

Substances

  • Antineoplastic Agents, Immunological
  • Ipilimumab
  • Nivolumab

Associated data

  • ClinicalTrials.gov/NCT02477826