Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743
Abstract
In this 5-year follow-up from the CheckMate 743 study in patients with unresectable pleural mesothelioma (PM), we evaluated updated efficacy and safety outcomes and biomarkers and performed treatment-switching analyses with first-line nivolumab plus ipilimumab versus chemotherapy. With a median follow-up of 66.8 months, nivolumab plus ipilimumab demonstrated continued overall survival (OS) benefit versus chemotherapy in all randomly assigned patients (5-year OS rates, 14% v 6%; hazard ratio [HR], 0.74 [95% CI, 0.62 to 0.88]); similar benefit was observed regardless of tumor histology. Of biomarker-evaluable patients treated with nivolumab plus ipilimumab (n = 242), high baseline monocytic myeloid-derived suppressor cell (M-MDSC) levels correlated with worse OS versus low M-MDSC levels (HR, 1.25 [95% CI, 1.09 to 1.43]). After adjusting for 24% of patients in the chemotherapy arm who received subsequent immunotherapy, nivolumab plus ipilimumab demonstrated continued OS benefit versus chemotherapy (HR, 0.64 [95% CI, 0.53 to 0.78]). No new safety signals were observed. These results demonstrate long-term, durable clinical benefit with nivolumab plus ipilimumab versus chemotherapy, which continued to be preserved even after treatment-switching adjustment in the chemotherapy arm. Exploratory analyses suggested greater benefit with nivolumab plus ipilimumab in the low M-MDSC subgroup. These results further support first-line nivolumab plus ipilimumab as standard of care for unresectable PM.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Arnaud Scherpereel
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Paul Baas
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Anna K. Nowak
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Anne S. Tsao
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Nobukazu Fujimoto
Solange Peters
Aaron S. Mansfield
Sanjay Popat
Yolanda Bautista Aragon
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Toby Talbot
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Francesco Grossi
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Dariusz Kowalski
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy, Klinika Nowotworow Pluca i Klatki Piersiowej, Warsaw, Poland
Muhammet A. Kaplan
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Andrés Felipe Cardona
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Raheela Soomro
3Cogent Biosciences Inc., Waltham, United States
Nan Hu
Adam Lee
Division of Cardiology (G.M.M., E.P.G., H.H., A.L., J.M., G.W., K.C., M.Y., G.M.), University of California, San Francisco.
Virginia Ip
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Yu-Han Hung
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...
Gérard Zalcman
Arnaud Scherpereel, MD, PhD, CHU Lille, Univ. Lille, Inserm, U1366-UMR9020—CRCLille—Cancer Research Center of Lille, OncoThAI, ONCOLille, Lille, France; Aaron S. Mansfield, MD, Mayo Clinic, Rochester, MN; Francesco Grossi, MD, Medical Oncology Division, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy; Sanjay Popat, PhD, FRCP, The Royal Marsden Hospital, London, United Kingdom; Paul Baas, MD, PhD, The Netherlands Cancer Institute and Leiden University Medical Center, Amsterdam, the Netherlands; Anna K. Nowak, PhD, MBBS, University of Western Australia, Perth, WA, Australia; Anne S. Tsao, MD, MBA, University of Texas MD Anderson Cancer Center, Houston, TX; Nobukazu Fujimoto, MD, PhD, Okayama Rosai Hospital, Okayama, Japan; Solange Peters, MD, PhD, Lausanne University Hospital, Lausanne, Switzerland; Yolanda Bautista Aragon, MD, Centro Médico Nacional Siglo XXI, Mexico City, Mexico; Toby Talbot, MD, The Sunrise Centre, Royal Cornwall Hospitals NHS Trust, Truro, Unite...