OncoTargets and Therapy (Dec 2022)
Clinical Impact of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Associated Clostridioides difficile Infection Among Patients with Lung Cancer
Abstract
Ying-Shan Chung,1,2 Yu-Ching Lin,3,4 Ming-Szu Hung,3– 5 Meng-Chin Ho,3 Yu-Hung Fang2,3 1Department of Pharmacy, Chang Gung Memorial Hospital, Puzi City, Taiwan, Republic of China; 2Department of Nursing, Chang Gung University of Science and Technology, Puzi City, Taiwan, Republic of China; 3Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Puzi City, Taiwan, Republic of China; 4Department of Respiratory Care, Chang Gung University of Science and Technology, Puzi City, Taiwan, Republic of China; 5School of Medicine, College of Medicine, Chang Gung University; Guishan Township, Taoyuan, Taiwan, Republic of ChinaCorrespondence: Yu-Hung Fang, Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi Branch, No. 6, W. Sec., Jiapu Road, Puzi City, Chiayi County, 61363, Taiwan, Republic of China, Tel +886-5-362-1000 ext. 2762, Fax +886-5-362-3005, Email [email protected]: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs)-associated Clostridioides difficile infection (CDI) among lung cancer patients have been reported in case reports and adverse events reporting system databases in the United States and Japan, but clinical data remained insufficient. This study aims to evaluate CDI in lung cancer patients receiving EGFR-TKIs.Methods: We conducted a retrospective cohort study using multi-institutional electronic medical records database. We included patients aged older than 20 years diagnosed with lung cancer and treated with EGFR-TKIs (gefitinib, erlotinib, afatinib). We defined EGFR-TKI initiation date as the index date and occurrence of diarrhea with CDI or without CDI as the event date. We followed patients from the index date until the event date, ICU admission, death, or 12/31/2019.Results: We included 2242 diarrhea patients, 51 were EGFR-TKI with CDI cohort, and 2191 were diarrhea without CDI cohort. Patients who were concurrently taking antibiotics (hazard ratio [HR], 3.30; 95% CI, 1.67– 6.5) and systemic steroids (HR, 4.9; 95% CI, 2.65– 9.06) had an increased risk of CDI. First-generation EGFR-TKIs tended to be associated with an increased risk of CDI compared with afatinib (HR, 1.81, 95% CI, 0.94– 3.47). EGFR-TKI with CDI had a higher ICU admission rate (HR, 3.42, 95% CI, 1.98– 5.91) and mortality rate (HR, 2.34, 95% CI, 1.67– 3.28) than diarrhea without CDI.Conclusion: Patients with CDI had higher ICU admission rates and mortality rates than those without CDI. Concurrent use of antibiotics and systemic steroids were risk factors for CDI among patients with lung cancer receiving EGFR-TKIs. Afatinib was not associated with a higher risk of CDI than first-generation EGFR-TKIs.Keywords: Clostridioides difficile infection, CDI, epidermal growth factor receptor tyrosine kinase inhibitors, EGFR-TKIs, lung cancer
