TY - JOUR
T1 - Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma
AU - Quispel-Janssen, Josine
AU - van der Noort, Vincent
AU - de Vries, Jeltje F.
AU - Zimmerman, Marion
AU - Lalezari, Ferry
AU - Thunnissen, Erik
AU - Monkhorst, Kim
AU - Schouten, Robert
AU - Schunselaar, Laurel
AU - Disselhorst, Maria
AU - Klomp, Houke
AU - Hartemink, Koen
AU - Burgers, Sjaak
AU - Buikhuisen, Wieneke
AU - Baas, Paul
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85050396674&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29908324
U2 - https://doi.org/10.1016/j.jtho.2018.05.038
DO - https://doi.org/10.1016/j.jtho.2018.05.038
M3 - Article
C2 - 29908324
SN - 1556-0864
VL - 13
SP - 1569
EP - 1576
JO - Journal of thoracic oncology
JF - Journal of thoracic oncology
IS - 10
ER -