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Curated Journal Articles on Mesothelioma

PD-1 blockade with nivolumab in patients with recurrent Malignant Pleural Mesothelioma

Journal of Thoracic Oncology 2018 June 13 [Link]

Quispel-Janssen J, van der Noort V, de Vries JF, Zimmerman M, Lalezari F, Thunnissen E, Monkhorst K, Schouten R, Schunselaar L, Disselhorst M, Klomp H, Hartemink K, Burgers S, Buikhuisen W, Baas P

Abstract

BACKGROUND:
Malignant Pleural Mesothelioma (MPM) has limited treatment options and a poor outcome. PD-1/PD-L1 checkpoint inhibitors have proven efficacious in several cancer types. Nivolumab is a fully humanized monoclonal antibody against PD-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 3mg/kg i.v. every two weeks. Primary endpoint was the disease control rate (DCR) at 12 weeks. Pre- and on-treatment biopsies were taken to analyze biomarkers for response.
RESULTS:
Of the 34 patients included, eight patients (24%) had a partial response at 12 weeks and another eight had stable disease (SD) resulting in a DCR at 12 weeks of 47%. One reached a PR at 18 weeks. In four patients with SD, the tumor remained stable for more than 6 months. Treatment-related adverse events (TR-AE) of any grade occurred in 26 patients (76%), most commonly fatigue (29%) and pruritus (15%). Grade 3 and 4 TR-AE were reported in 9 patients (26%), with pneumonitis, gastro-intestinal 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 9 samples (27%), but did not correlate with outcome.
INTERPRETATION:
Single agent nivolumab has meaningful clinical efficacy and a manageable safety profile in pretreated patients with mesothelioma. PD-L1 expression does not predict for response in this population.

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