The association between aspirin use and immune-related adverse events in specific cancer patients receiving ICIs therapy: analysis of the FAERS database

Our plain-English summary of The association between aspirin use and immune-related adverse events in specific cancer patients receiving ICIs therapy: analysis of the FAERS database, by H. Yang, Z. Liu, R. Li, et al (Frontiers in Pharmacology, 2023).

The study

• Authors: H. Yang, Z. Liu, R. Li, R. Huang, X. Peng
• Journal: Frontiers in Pharmacology
• Published: 2023;14:1259628
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The promise of immune checkpoint inhibitors (ICIs) therapy in cancer treatment is tempered by the occurrence of immune-related adverse events (irAEs). Many patients undergoing ICIs also take aspirin, but the association between aspirin and irAEs is not well understood. Methods: This study analyzed adverse reaction data associated with the use of ICIs in the US Food and Drug Administration (FDA) Adverse Event Reporting System FDA Adverse Event Reporting System database, from the approval date of each drug until 1 October 2022. Multivariate logistic regression was employed to assess the association of aspirin use with irAEs in patients receiving ICIs. Results: The results indicated that aspirin use was associated with an increased risk of irAEs in a pan-cancer analysis, with a more pronounced association in specific cancer types such as lung cancer, mesothelioma, and pancreatic cancer. However, in lymphoma, aspirin use was associated with a reduced risk of irAEs. Furthermore, aspirin use was associated with an increased risk of certain irAEs, such as anemia, colitis, myocarditis, myositis, pancreatitis, pericarditis, and pneumonia, while it was associated with a reduced risk of rash, Stevens-Johnson syndrome, and thyroiditis. Conclusion: This study has unveiled an association between aspirin use and irAEs in cancer patients receiving ICIs therapy, emphasizing the need for individualized consideration of patients' medication history when devising cancer treatment plans to enhance efficacy and reduce risks.

Copyright © 2023 Yang, Liu, Li, Huang and Peng.

In plain English

This study analyzed reports to the US Food and Drug Administration Adverse Event Reporting System (FAERS) about cancer patients treated with immune checkpoint inhibitors, a type of immunotherapy. The reports ran from each drug's approval until 1 October 2022. Of 123,104 patients, 5,359 (4.4%) also took aspirin. The authors used statistical models adjusted for age, sex, immunotherapy drug and treatment regimen to compare immune-related side effects in aspirin users and non-users. Across all cancers, aspirin use was associated with higher odds of these side effects (odds ratio 1.18, 95% CI 1.10 to 1.26). In the mesothelioma group (70 aspirin users, 1,256 non-users) the odds ratio was 2.90 (95% CI 1.75 to 4.82). Higher odds were also found in lung and pancreatic cancer. Lymphoma showed lower odds (odds ratio 0.27, 95% CI 0.11 to 0.67). The article did not say which type of mesothelioma was included, and did not study asbestos exposure. The authors concluded that aspirin use was associated with these side effects and that the association varied by cancer type, side effect and drug. They noted that the reports lack details such as aspirin dose and duration.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of adverse event reports in the FDA Adverse Event Reporting System (FAERS), using multivariable logistic regression
• Who was studied: 123,104 cancer patients in FAERS reports involving immune checkpoint inhibitors, from each drug's FDA approval date until 1 October 2022; 24 cancer types analyzed separately, including mesothelioma
• Exposure: Aspirin use during treatment with immune checkpoint inhibitors (PD-1, PD-L1, CTLA-4, LAG-3 and PD-1/LAG-3 inhibitors); 5,359 patients (4.4%) reported taking aspirin. No asbestos exposure was studied.
• Main results:
  • Across all cancer types, aspirin use was associated with increased odds of immune-related adverse events: OR 1.18, 95% CI 1.10 to 1.26, FDR adjusted p less than 0.001
  • In mesothelioma patients, aspirin use was associated with increased odds of immune-related adverse events: OR 2.90, 95% CI 1.75 to 4.82, FDR adjusted p less than 0.001
  • The mesothelioma group comprised 70 aspirin users (1.3% of aspirin users) and 1,256 non-users (1.1% of non-users)
  • In lung cancer patients, aspirin use was associated with increased odds: OR 1.24, 95% CI 1.10 to 1.40, FDR adjusted p = 0.003
  • In pancreatic cancer patients, aspirin use was associated with increased odds: OR 2.51, 95% CI 1.79 to 3.51
  • In lymphoma patients, aspirin use was associated with lower odds: OR 0.27, 95% CI 0.11 to 0.67, FDR adjusted p = 0.029
  • Among patients on PD-1 inhibitors, aspirin use in mesothelioma was associated with increased odds: OR 3.01, 95% CI 1.57 to 5.76, FDR adjusted p = 0.013
  • For specific side effects across all patients, aspirin use was associated with higher odds of colitis (OR 1.46, 95% CI 1.27 to 1.66) and pneumonitis (OR 1.60, 95% CI 1.39 to 1.84), and lower odds of rash (OR 0.68, 95% CI 0.56 to 0.82), among others
  • Among patients on PD-L1 inhibitors, the all-cancer association was not statistically significant
  • Among patients on CTLA-4 inhibitors, the only statistically significant result was in pancreatic cancer (OR 2.91, 95% CI 1.71 to 4.96)
• The authors' conclusion: The authors concluded that aspirin use was significantly associated with immune-related adverse events in cancer patients receiving immune checkpoint inhibitors. They stated that the association varied by cancer type, type of adverse event and type of drug, and that baseline medications such as aspirin should be assessed when planning treatment.
• Limitations the authors state:
  • FAERS is a voluntary, passive reporting system, with incomplete, inaccurate, inconsistent and delayed reports
  • The data lack details such as the dose and duration of aspirin use, other treatments received, and the sequence of medication
  • Cases were unevenly distributed, with many lung cancer patients and far fewer patients with other cancers, which may introduce bias and limit generalizability
  • The lymphoma finding rests on a small subgroup (1.5% of the study population) and may be a statistical anomaly
  • A patient's history of cardiovascular conditions, for which aspirin is widely used, may itself contribute to the higher risk
  • The mechanisms linking aspirin use to these adverse events remain unclear

Topics

Medical terms in this study, explained in our Lexicon: Immune-Related Adverse Events, checkpoint inhibitors, Lung Cancer, Mesothelioma.

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