Is there an interplay between immune checkpoint inhibitors, thromboprophylactic treatments and thromboembolic events? Mechanisms and impact in non-small cell lung cancer patients

Federico Nichetti, Francesca Ligorio, Emma Zattarin, Diego Signorelli, Arsela Prelaj, Claudia Proto, Giulia Galli, Antonio Marra, Giulia Apollonio, Luca Porcu, Filippo de Braud, Giuseppe Lo Russo, Roberto Ferrara, Marina Chiara Garassino

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number67
JournalCancers
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2019

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Keywords

  • Aspirin
  • Immune checkpoint inhibitors
  • Immunotherapy
  • Non-small cell lung cancer
  • Thromboembolic events
  • Thromboprophylaxis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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