Risk of Treatment-related Toxicity from EGFR Tyrosine Kinase Inhibitors: a Systematic Review and Network Meta-analysis of Randomized Clinical Trials in -mutant Non-small Cell Lung Cancer

Overview

Journal J Thorac Dis

Publisher AME Publishing Company

Specialty Pulmonary Medicine

Date 2024 Nov 18

PMID 39552885

Authors

Zhifei Li

Hongyuan Chu

Sicheng Huang

Runze Li

Bin Qiu

Fengwei Tan

Qi Xue

Shugeng Gao

Jie He

Affiliations

Soon will be listed here.

Abstract

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective for non-small cell lung cancer (NSCLC) patients with -mutation, while their toxicity profiles are non-negligible and inconsistent. This study aimed to assess the toxicity intensity and profiles of different EGFR-TKIs in NSCLC patients with -mutation.

Methods: This random-effect Bayesian framed network meta-analysis (NMA) only included exclusively randomized clinical trials with demonstrated evidence on safety of EGFR-TKIs in NSCLC patients with EGFR-mutation. Pooled odds ratios and surface under the cumulative ranking curve (SUCRA) were calculated to depict the toxicity map of EGFR-TKIs.

Results: This review included 23 randomized clinical trials incorporating 7,006 patients and 11 treatments: erlotinib, gefitinib, icotinib, afatinib, dacomitinib, osimertinib, furmonertinib, aumolertinib, pemetrexed-free chemotherapy (PfCT), pemetrexed-based chemotherapy (PbCT) and placebo. Overall, chemotherapy and second-generation EGFR-TKIs exhibited higher toxicity. A toxicity sequence according to the likelihood of causing grade ≥3 adverse events (AEs) was identified as follows: PfCT > PbCT > afatinib > dacomitinib > erlotinib > aumolertinib > gefitinib > furmonertinib > osimertinib > placebo > icotinib. For discontinuation due to AEs, among EGFR-TKIs, icotinib and afatinib demonstrated best and second-best safety profiles according to pooled odds ratios and SUCRA. Regarding specific toxicity, EGFR-TKIs demonstrated variable toxicity intensity and different predominate toxicity spectrums.

Conclusions: This is the first study to depict the difference in toxicity of EGFR-TKIs in a population with EGFR-mutant NSCLC. In general, osimertinib and icotinib were associated with favorable safety compared with other EGFR-TKIs. Difference in safety between the third-generation EGFR-TKIs was also first investigated comprehensively. Furthermore, this review elaborated the varied predominate spectrum and ranked the toxicity of EGFR-TKIs for providing toxicity rationale for treatment decisions.

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