Fatal toxic effects related to EGFR tyrosine kinase inhibitors based on 53 cohorts with 9,569 participants

Xianhe Xie; Xuewen Wang; Sumei Wu; Haitao Yang; Junjin Liu; Huijuan Chen; Yin Ding; Liting Ling; Heng Lin

doi:10.21037/jtd-19-4000A

Fatal toxic effects related to EGFR tyrosine kinase inhibitors based on 53 cohorts with 9,569 participants

J Thorac Dis. 2020 Aug;12(8):4057-4069. doi: 10.21037/jtd-19-4000A.

Authors

Xianhe Xie¹, Xuewen Wang², Sumei Wu¹, Haitao Yang¹, Junjin Liu¹, Huijuan Chen¹, Yin Ding¹, Liting Ling¹, Heng Lin¹

Affiliations

¹ Department of Chemotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
² Department of Oncology, The 900th Hospital of the People's Liberation Army Joint Service Support Force, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China.

Abstract

Background: To estimate the incidence and susceptible factors of fatal toxic effects related to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).

Methods: PubMed and Embase were thoroughly searched for clinical trials based on the following terms and corresponding Medical Subject Heading ones: "erlotinib", "gefitinib", "afatinib", "dacomitinib", "osimertinib", and "non-small-cell lung cancer (NSCLC)". A total of 53 eligible cohorts with 9,569 participants were collected.

Results: A total of 105 cases of fatal toxic effects related to EGFR-TKIs occurred in 53 cohorts. The overall incidence was 1.33% [95% confidence interval (CI): 1.08-1.63%]. The odds and incidence were apparently higher in Japanese group (compared with non-East Asian group) [2.72 vs. 1.30, P=0.015; odds ratio (OR): 2.26, 95% CI: 1.17-4.37, P=0.015], in first-line treatment group (compared with EGFR-TKI retreatment group) (1.54 vs. 0.69, P=0.028; OR: 2.41, 95% CI: 1.10-5.26, P=0.028), and in the trial phase II (compared with trial phase III) (1.82% vs. 1.11%, P=0.009; OR: 1.73, 95% CI: 1.15-2.62, P=0.009). Notably, the Japanese group was higher than non-East Asian group after controlling for the treatment-line and trial phase (OR: 2.16, 95% CI: 1.12-4.16, P=0.022). Interstitial lung disease (ILD) was predominant in 29 fatal causes followed by pneumonia, respiratory failure and diarrhea.

Conclusions: The overall incidence of fatal toxic effects related to EGFR-TKIs was 1.33%, and the major fatal cause was ILD, followed by pneumonia, respiratory failure and diarrhea. The susceptible factor of fatal toxic effects related to EGFR-TKIs was the Japanese group. This study provided a capability for clinicians to predict and detect high-risk populations of fatal toxic effects.

Keywords: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs); fatal toxic effects; meta-analysis.