Josine Quispel-Janssen1, Vincent van der Noort2, Jeltje F de Vries2, Marion Zimmerman3, Ferry Lalezari4, Erik Thunnissen5, Kim Monkhorst6, Robert Schouten3, Laurel Schunselaar7, Maria Disselhorst3, Houke Klomp8, Koen Hartemink8, Sjaak Burgers3, Wieneke Buikhuisen3, Paul Baas3. 1. Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: thoraxoncologie@nki.nl. 2. Biometrics Department, Netherlands Cancer Institute, Amsterdam, The Netherlands. 3. Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 4. Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 5. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. 6. Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 7. Division of Oncogenomics, Oncode Institute within Netherlands Cancer Institute, Amsterdam, The Netherlands. 8. Department of Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract
INTRODUCTION: Malignant pleural mesothelioma (MPM) has limited treatment options and a poor outcome. Programmed death 1/programmed death ligand 1 (PD-L1) checkpoint inhibitors have proven efficacious in several cancer types. Nivolumab is a fully humanized monoclonal antibody against programmed death 1 with a favorable toxicity profile. In MPM, the immune system is considered to play an important role. We therefore tested nivolumab in recurrent MPM. METHODS: In this single-center trial, patients with MPM received nivolumab 3 mg/kg intravenously every 2 weeks. Primary endpoint was the disease control rate at 12 weeks. Pre- and on-treatment biopsy specimens were obtained to analyze biomarkers for response. RESULTS: Of the 34 patients included, 8 patients (24%) had a partial response at 12 weeks and another 8 had stable disease resulting in a disease control rate at 12 weeks of 47%. One reached a partial response at 18 weeks. In 4 patients with stable disease, the tumor remained stable for more than 6 months. Treatment-related adverse events of any grade occurred in 26 patients (76%), most commonly fatigue (29%) and pruritus (15%). Grades 3 and 4 treatment-related adverse events were reported in 9 patients (26%), with pneumonitis, gastrointestinal disorders, and laboratory disorders mostly seen. One treatment-related death was due to pneumonitis and probably initiated by concurrent amiodarone therapy. PD-L1 was expressed on tumor cells in nine samples (27%), but did not correlate with outcome. CONCLUSIONS: Single-agent nivolumab has meaningful clinical efficacy and a manageable safety profile in pre-treated patients with mesothelioma. PD-L1 expression does not predict for response in this population.
INTRODUCTION:Malignant pleural mesothelioma (MPM) has limited treatment options and a poor outcome. Programmed death 1/programmed death ligand 1 (PD-L1) checkpoint inhibitors have proven efficacious in several cancer types. Nivolumab is a fully humanized monoclonal antibody against programmed death 1 with a favorable toxicity profile. In MPM, the immune system is considered to play an important role. We therefore tested nivolumab in recurrent MPM. METHODS: In this single-center trial, patients with MPM received nivolumab 3 mg/kg intravenously every 2 weeks. Primary endpoint was the disease control rate at 12 weeks. Pre- and on-treatment biopsy specimens were obtained to analyze biomarkers for response. RESULTS: Of the 34 patients included, 8 patients (24%) had a partial response at 12 weeks and another 8 had stable disease resulting in a disease control rate at 12 weeks of 47%. One reached a partial response at 18 weeks. In 4 patients with stable disease, the tumor remained stable for more than 6 months. Treatment-related adverse events of any grade occurred in 26 patients (76%), most commonly fatigue (29%) and pruritus (15%). Grades 3 and 4 treatment-related adverse events were reported in 9 patients (26%), with pneumonitis, gastrointestinal disorders, and laboratory disorders mostly seen. One treatment-related death was due to pneumonitis and probably initiated by concurrent amiodarone therapy. PD-L1 was expressed on tumor cells in nine samples (27%), but did not correlate with outcome. CONCLUSIONS: Single-agent nivolumab has meaningful clinical efficacy and a manageable safety profile in pre-treated patients with mesothelioma. PD-L1 expression does not predict for response in this population.
Authors: Runzhe Chen; Won-Chul Lee; Anne S Tsao; Jianjun Zhang; Junya Fujimoto; Jun Li; Xin Hu; Reza Mehran; David Rice; Stephen G Swisher; Boris Sepesi; Hai T Tran; Chi-Wan Chow; Latasha D Little; Curtis Gumbs; Cara Haymaker; John V Heymach; Ignacio I Wistuba; J Jack Lee; P Andrew Futreal; Jianhua Zhang; Alexandre Reuben Journal: Clin Cancer Res Date: 2020-08-14 Impact factor: 12.531
Authors: Yucai Wang; Shouhao Zhou; Fang Yang; Xinyue Qi; Xin Wang; Xiaoxiang Guan; Chan Shen; Narjust Duma; Jesus Vera Aguilera; Ashish Chintakuntlawar; Katharine A Price; Julian R Molina; Lance C Pagliaro; Thorvardur R Halfdanarson; Axel Grothey; Svetomir N Markovic; Grzegorz S Nowakowski; Stephen M Ansell; Michael L Wang Journal: JAMA Oncol Date: 2019-07-01 Impact factor: 31.777