First-line nivolumab plus ipilimumab versus chemotherapy for the treatment of unresectable malignant pleural mesothelioma: patient-reported outcomes in CheckMate 743

Arnaud Scherpereel; Scott Antonia; Yolanda Bautista; Francesco Grossi; Dariusz Kowalski; Gérard Zalcman; Anna K Nowak; Nobukazu Fujimoto; Solange Peters; Anne S Tsao; Aaron S Mansfield; Sanjay Popat; Xiaowu Sun; Rachael Lawrance; Xiaoqing Zhang; Melinda J Daumont; Bryan Bennett; Mike McKenna; Paul Baas

doi:10.1016/j.lungcan.2022.03.012

First-line nivolumab plus ipilimumab versus chemotherapy for the treatment of unresectable malignant pleural mesothelioma: patient-reported outcomes in CheckMate 743

Lung Cancer. 2022 May:167:8-16. doi: 10.1016/j.lungcan.2022.03.012. Epub 2022 Mar 21.

Authors

Arnaud Scherpereel¹, Scott Antonia², Yolanda Bautista³, Francesco Grossi⁴, Dariusz Kowalski⁵, Gérard Zalcman⁶, Anna K Nowak⁷, Nobukazu Fujimoto⁸, Solange Peters⁹, Anne S Tsao¹⁰, Aaron S Mansfield¹¹, Sanjay Popat¹², Xiaowu Sun¹³, Rachael Lawrance¹⁴, Xiaoqing Zhang¹⁵, Melinda J Daumont¹⁶, Bryan Bennett¹⁷, Mike McKenna¹⁸, Paul Baas¹⁹

Affiliations

¹ Pulmonary and Thoracic Oncology Department, University of Lille, CHU Lille, INSERM, OncoThAI, Institut Coeur Poumon, Boulevard du Professeur Jules Leclercq, 59037 Lille, France. Electronic address: [email protected].
² Thoracic Oncology Department, H. Lee Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA. Electronic address: [email protected].
³ Centro Médico Nacional Siglo XXI, Av. Cuauhtémoc 330, Doctores, Cuauhtémoc, 06720 Mexico City, Mexico. Electronic address: [email protected].
⁴ UOS Tumori Polmonari, Largo Rosanna Benzi, 10, 16132 Genova, Italy. Electronic address: [email protected].
⁵ Maria Sklodowska-Curie National Research Institute of Oncology, Wawelska 15 B, 00-001 Warsaw, Poland. Electronic address: [email protected].
⁶ Thoracic Oncology Department, Université de Paris, 17 Rue Jean Antoine de Baïf, 75013 Paris, France. Electronic address: [email protected].
⁷ Medical School, University of Western Australia and Sir Charles Gairdner Hospital, 35 Stirling Highway, 6009 Perth, Australia. Electronic address: [email protected].
⁸ Medical Oncology, Okayama Rosai Hospital, 1 Chome-10-25 Chikkomidorimachi, Minami Ward, Okayama, Japan. Electronic address: [email protected].
⁹ Oncology Department, Lausanne University Hospital, Rue du Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: [email protected].
¹⁰ Department of Thoracic-Head & Neck Medical Oncology, MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. Electronic address: [email protected].
¹¹ Medical Oncology, Mayo Clinic, 200 First St., SW, Rochester, MN 55905, USA. Electronic address: [email protected].
¹² Lung Unit, Royal Marsden Hospital, London, Institute of Cancer Research, Fulham Road, London SW3 6JJ, UK. Electronic address: [email protected].
¹³ Adelphi Values, 290 Congress St., Boston, MA 02210, USA. Electronic address: [email protected].
¹⁴ Adelphi Values, 290 Congress St., Boston, MA 02210, USA. Electronic address: [email protected].
¹⁵ Bristol Myers Squibb, 3551 Lawrenceville Rd., Princeton, NJ 08540, USA. Electronic address: [email protected].
¹⁶ Bristol Myers Squibb, Avenue de Finlande 4, 1420 Braine-l'Alleud, Belgium. Electronic address: [email protected].
¹⁷ Bristol Myers Squibb, Sanderson Rd., Uxbridge UB8 1DH, UK. Electronic address: [email protected].
¹⁸ Health Outcomes Solutions, Radius House, 51 Clarendon Road, Watford WD17 1HP, UK. Electronic address: [email protected].
¹⁹ Department of Thoracic Oncology, The Netherlands Cancer Institute and Leiden University Medical Center, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address: [email protected].

PMID: 35367910
DOI: 10.1016/j.lungcan.2022.03.012

Abstract

Objective: In CheckMate 743 (NCT02899299), nivolumab + ipilimumab significantly prolonged overall survival in patients with unresectable malignant pleural mesothelioma (MPM). We present patient-reported outcomes (PROs).

Materials and methods: Patients (N = 605) were randomized to nivolumab + ipilimumab or chemotherapy. Changes in disease-related symptom burden and health-related quality of life (HRQoL) were evaluated descriptively using the Lung Cancer Symptom Scale (LCSS)-Mesothelioma (Meso) average symptom burden index (ASBI), LCSS-Meso 3-item global index (3-IGI), 3-level EuroQol 5-dimensional (EQ-5D-3L) visual analog score (VAS), and EQ-5D-3L utility index. PROs were assessed at baseline and every 2 (nivolumab + ipilimumab) or 3 weeks (chemotherapy) through 12 weeks, every 6 weeks through 12 months, every 12 weeks thereafter, and at specified follow-ups. Mixed-effect model repeated measures (MMRM) and time to deterioration analyses were conducted.

Results: Completion rates were generally >80%. LCSS-Meso ASBI mean changes from baseline trended to improve over time with nivolumab + ipilimumab and deteriorate with chemotherapy, but did not meet clinically important difference thresholds [±10 score change]. EQ-5D-3L VAS mean scores improved over time with nivolumab + ipilimumab; by week 60, patients had scores consistent with United Kingdom normal population values. MMRM analyses favored nivolumab + ipilimumab for all individual symptoms except cough. Nivolumab + ipilimumab delayed time to definitive deterioration in HRQoL (hazard ratio 0.52 [95% confidence interval 0.36-0.74]) and showed a trend in symptom delay versus chemotherapy.

Conclusions: Nivolumab + ipilimumab decreased the risk of deterioration in disease-related symptoms and HRQoL versus chemotherapy and maintained QoL in patients with unresectable MPM.

Keywords: Anti-cytotoxic T lymphocyte antigen-4 (CTLA-4); EQ-5D; Immune checkpoint inhibitors; Immuno-oncology; Immunotherapy; Lung Cancer Symptom Scale; Overall survival; Programmed cell death (PD)-1 inhibitor; Quality of life; Symptom burden.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / adverse effects
Humans
Ipilimumab / therapeutic use
Lung Neoplasms* / diagnosis
Lung Neoplasms* / drug therapy
Lung Neoplasms* / etiology
Mesothelioma* / drug therapy
Mesothelioma, Malignant*
Nivolumab / adverse effects
Patient Reported Outcome Measures
Quality of Life

Substances

Ipilimumab
Nivolumab

Associated data

ClinicalTrials.gov/NCT02899299