Gemcitabine Synergizes with Immune Checkpoint Inhibitors and Overcomes Resistance in a Preclinical Model and Mesothelioma Patients

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Paulino Tallón de LaraAlessandra Curioni-Fontecedro

Abstract

Combination of immune checkpoint inhibitors with chemotherapy is under investigation for cancer treatment. We studied the rationale of such a combination for treating mesothelioma, a disease with limited treatment options. The combination of gemcitabine and immune checkpoint inhibitors outperformed immunotherapy alone with regard to tumor control and survival in a preclinical mesothelioma model; however, the addition of dexamethasone to gemcitabine and immune checkpoint inhibitors nullified the synergistic clinical response. Furthermore, treatment with gemcitabine plus anti-PD-1 resulted in an objective clinical response in two patients with mesothelioma, who were resistant to gemcitabine or anti-PD-1 as monotherapy. Thus, treatment of mesothelioma with a combination of gemcitabine with immune checkpoint inhibitors is feasible and results in synergistic clinical response compared with single treatment in the absence of steroids.

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Citations

May 3, 2019·Expert Opinion on Biological Therapy·Anna K NowakAlistair Cook
Sep 22, 2020·Expert Opinion on Biological Therapy·Gerhard Hamilton
Jan 26, 2020·Pharmaceutics·Jan DörrieBeatrice Schuler-Thurner
Oct 21, 2020·Nature Metabolism·Lisa Maria KochReinhard Dechant
May 1, 2021·Journal of Clinical Medicine·Alejandro Olivares-HernándezJosé Pablo Miramontes-González
Sep 13, 2020·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Kyung-Ho JungKyung-Han Lee
Apr 4, 2021·Cancer Discovery·Timothy A YapHussein A Tawbi
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Feb 17, 2020·NAR Cancer·Christian BaillyBruno Quesnel
Oct 13, 2021·Cancer Discovery·Amit GroverDmitry I Gabrilovich

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