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Article

Is There an Interplay between Immune Checkpoint Inhibitors, Thromboprophylactic Treatments and Thromboembolic Events? Mechanisms and Impact in Non-Small Cell Lung Cancer Patients

by
Federico Nichetti
1,*,
Francesca Ligorio
1,
Emma Zattarin
1,
Diego Signorelli
1,
Arsela Prelaj
1,
Claudia Proto
1,
Giulia Galli
1,
Antonio Marra
2,
Giulia Apollonio
1,
Luca Porcu
3,
Filippo de Braud
1,4,
Giuseppe Lo Russo
1,
Roberto Ferrara
1 and
Marina Chiara Garassino
1
1
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
2
Department of Medical Oncology, Istituto Europeo di Oncologia, 20141 Milan, Italy
3
Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy
4
Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 67; https://doi.org/10.3390/cancers12010067
Submission received: 2 December 2019 / Revised: 19 December 2019 / Accepted: 20 December 2019 / Published: 25 December 2019
(This article belongs to the Collection Mechanism of Immunotherapy in Cancers)
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Abstract

PD-1 pathway blockade has been shown to promote proatherogenic T-cell responses and destabilization of atherosclerotic plaques. Moreover, preclinical evidence suggests a potential synergy of antiplatelet drugs with immune checkpoint inhibitors (ICIs). We conducted an analysis within a prospective observational protocol (APOLLO study) to investigate the rates, predictors, and prognostic significance of thromboembolic events (TE) and thromboprophylaxis in patients with advanced NSCLC treated with ICIs. Among 217 patients treated between April 2014 and September 2018, 13.8% developed TE events. Current smoking status (HR 3.61 (95% CI 1.52–8.60), p = 0.004) and high (>50%) PD-L1 (HR 2.55 (95% CI 1.05–6.19), p = 0.038) resulted in being independent TE predictors. An increased risk of death following a diagnosis of TE (HR 2.93; 95% CI 1.59–5.42; p = 0.0006) was observed. Patients receiving antiplatelet treatment experienced longer progression-free survival (PFS) (6.4 vs. 3.4 months, HR 0.67 (95% CI 0.48–0.92), p = 0.015) and a trend toward better OS (11.2 vs. 9.6 months, HR 0.78 (95% CI 0.55–1.09), p = 0.14), which were not confirmed in a multivariate model. No impact of anticoagulant treatment on patients’ outcomes was observed. NSCLC patients treated with ICIs bear a consistent risk for thrombotic complications, with a detrimental effect on survival. The impact of antiplatelet drugs on ICIs efficacy deserves further investigation in prospective trials.
Keywords: immunotherapy; immune checkpoint inhibitors; thromboprophylaxis; aspirin; thromboembolic events; non-small cell lung cancer immunotherapy; immune checkpoint inhibitors; thromboprophylaxis; aspirin; thromboembolic events; non-small cell lung cancer

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MDPI and ACS Style

Nichetti, F.; Ligorio, F.; Zattarin, E.; Signorelli, D.; Prelaj, A.; Proto, C.; Galli, G.; Marra, A.; Apollonio, G.; Porcu, L.; et al. Is There an Interplay between Immune Checkpoint Inhibitors, Thromboprophylactic Treatments and Thromboembolic Events? Mechanisms and Impact in Non-Small Cell Lung Cancer Patients. Cancers 2020, 12, 67. https://doi.org/10.3390/cancers12010067

AMA Style

Nichetti F, Ligorio F, Zattarin E, Signorelli D, Prelaj A, Proto C, Galli G, Marra A, Apollonio G, Porcu L, et al. Is There an Interplay between Immune Checkpoint Inhibitors, Thromboprophylactic Treatments and Thromboembolic Events? Mechanisms and Impact in Non-Small Cell Lung Cancer Patients. Cancers. 2020; 12(1):67. https://doi.org/10.3390/cancers12010067

Chicago/Turabian Style

Nichetti, Federico, Francesca Ligorio, Emma Zattarin, Diego Signorelli, Arsela Prelaj, Claudia Proto, Giulia Galli, Antonio Marra, Giulia Apollonio, Luca Porcu, and et al. 2020. "Is There an Interplay between Immune Checkpoint Inhibitors, Thromboprophylactic Treatments and Thromboembolic Events? Mechanisms and Impact in Non-Small Cell Lung Cancer Patients" Cancers 12, no. 1: 67. https://doi.org/10.3390/cancers12010067

APA Style

Nichetti, F., Ligorio, F., Zattarin, E., Signorelli, D., Prelaj, A., Proto, C., Galli, G., Marra, A., Apollonio, G., Porcu, L., de Braud, F., Lo Russo, G., Ferrara, R., & Garassino, M. C. (2020). Is There an Interplay between Immune Checkpoint Inhibitors, Thromboprophylactic Treatments and Thromboembolic Events? Mechanisms and Impact in Non-Small Cell Lung Cancer Patients. Cancers, 12(1), 67. https://doi.org/10.3390/cancers12010067

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