Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma

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 favo...

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Bibliographic Details
Published in:Journal of thoracic oncology 2018-10, Vol.13 (10), p.1569-1576
Main Authors: Quispel-Janssen, Josine, van der Noort, Vincent, de Vries, Jeltje F., Zimmerman, Marion, Lalezari, Ferry, Thunnissen, Erik, Monkhorst, Kim, Schouten, Robert, Schunselaar, Laurel, Disselhorst, Maria, Klomp, Houke, Hartemink, Koen, Burgers, Sjaak, Buikhuisen, Wieneke, Baas, Paul
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological - therapeutic use
Checkpoint inhibitor
Female
Humans
Immunotherapy
Lung Neoplasms - pathology
Male
Mesothelioma
Mesothelioma - pathology
Mesothelioma, Malignant
Middle Aged
Nivolumab
Nivolumab - pharmacology
Nivolumab - therapeutic use
Pleural Neoplasms - pathology
Programmed death ligand 1
Progression-Free Survival
Prospective Studies
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Summary: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. 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. 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. 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.
ISSN:1556-0864
1556-1380
DOI:10.1016/j.jtho.2018.05.038