According to patient reported outcomes (PROs), patients with unresectable malignant pleural mesothelioma fared better in terms of disease-related symptom burden and health-related quality of life (HRQoL) with nivolumab plus ipilimumab compared to chemotherapy administered in the first-line setting. These findings from the phase III CheckMate 743 study were presented at the ESMO Immuno-Oncology Virtual Congress 2020, held from 9 to 12 December 2020.
Professor Arnaud A. Scherpereel of the Pulmonary and Thoracic Oncology, University of Lille, CHU Lille, INSERM U1189, OncoThAI in Lille, France discussed PRO findings from the phase III randomised CheckMate 743 (NCT02899299) clinical trial. In CheckMate 743, statistically significant and clinically meaningful improvement in overall survival (OS) was demonstrated by nivolumab combined with ipilimumab compared to standard-of-care chemotherapy (median OS, 18.1 months vs 14.1 months, respectively) in patients with previously untreated, unresectable malignant pleural mesothelioma.
CheckMate 743 enrolled patients 18 years and older with previously untreated, malignant pleural mesothelioma. Following 1:1 randomisation, patients were treated with nivolumab at 3 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks for up to 2 years or platinum/pemetrexed chemotherapy every 3 weeks for 6 cycles.
PROs were assessed before administration of each dose of nivolumab or chemotherapy on day 1 of each cycle for 12 weeks, every 6 weeks for 12 months, every 12 weeks thereafter, and at specified follow-ups. The disease-related symptom burden was evaluated using the Lung Cancer Symptom Scale (LCSS)-Meso average symptom burden index (ASBI) and 3-item global index (3-IGI) and HRQoL was evaluated using the EQ-5D-3L utility index (UI) and visual analogue scale (VAS).
The analyses conducted included a summary of PROs, mixed-effect model repeated measures (MMRM), and time to deterioration.
PROs were exploratory endpoints in the study. Completion rates of the PROs were greater than 80% for most on-treatment timepoints across both arms for ≥10 patients up to week 96 for nivolumab plus ipilimumab and week 36 for chemotherapy.
Time to deterioration favoured nivolumab plus ipilimumab versus chemotherapy on all scales
MMRM analyses of differences in overall change from baseline between treatment arms for symptoms (LCSS-Meso ASBI) trended to improve over time with nivolumab plus ipilimumab and deteriorate with chemotherapy, although the mean changes did not meet the pre-specified clinically important difference thresholds of ±10 score change.
HR-QoL assessed using mean EQ-5D-3L VAS scores improved over time with nivolumab plus ipilimumab. While on treatment, patients reached UK population norms score (82.8).
Assessment of both on-treatment and follow-up data showed that nivolumab plus ipilimumab significantly delayed HRQoL deterioration as well as trended toward symptom delays when compared to chemotherapy.
The time to definitive deterioriation was prolonged with nivolumab plus ipilimumab versus chemotherapy according to the LCSS-Meso ASBI (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.36–0.74), the LCSS-Meso 3-IGI (HR 0.61; 95% CI 0.43–0.86), the EQ-5D-3L VAS (HR 0.58; 95% CI 0.45–0.75), and the EQ-5D-3L UI (HR 0.65; 95% CI 0.50–0.84).
Based on these results, the authors concluded that, overall, patients with previously untreated, unresectable malignant pleural mesothelioma, maintained quality of life and experienced a decreased risk of definitive deterioration in disease-related symptoms as well as HRQoL when treated with nivolumab plus ipilimumab as compared to chemotherapy. These data further support the use of nivolumab plus ipilimumab as first-line treatment for these patients.
Funding was reported from Bristol Myers Squibb.
LBA1 – Scherpereel A, Antonia S, Bautista Y, et al. First-line nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) for the treatment of unresectable malignant pleural mesothelioma (MPM): Patient-reported outcomes (PROs) from CheckMate 743. ESMO Immuno-Oncology Virtual Congress 2020 (9-12 December).