Toxicity profiles associated with EGFR-TKIs combined with angiogenesis inhibitors in non-small cell lung cancer: an epidemiological surveillance analysis of the FDA adverse event reporting system

Ongoing studies are evaluating the efficacy and toxicity profiles of combining epidermal growth factor receptor inhibitors (EGFR-TKIs) with antiangiogenic agents in non-small cell lung cancer (NSCLC). However, the complete toxicity profiles remain elusive. This study conducted an extensive pharmacovigilance analysis utilizing the FDA Adverse Event Reporting System database. The analysis focused on identifying and characterizing adverse events (AEs) associated with the concurrent use of EGFR-TKIs and antiangiogenic inhibitors in patients with NSCLC. The study identified significant occurrences of AEs linked to the combination therapy, particularly impacting general disorders, skin and subcutaneous tissue conditions, and vascular disorders. Frequently reported AEs included rash, diarrhea, fatigue, nausea, decreased appetite, and anemia. Notably, the combination of EGFR-TKIs with antiangiogenic inhibitors resulted in an increased incidence of AEs across multiple organ systems compared to EGFR-TKIs alone, with some adverse effects, such as anemia, arrhythmia, and ulcerative keratitis, persisting beyond one year in a subset of patients. The combination of EGFR-TKIs and antiangiogenic inhibitors in NSCLC treatment presents a distinct and substantial AE profile, often with delayed onset. This finding underscores the necessity for rigorous and ongoing monitoring protocols to mitigate potential long-term adverse effects.

目前已有多项正在开展的研究，旨在评估表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）联合抗血管生成药物治疗非小细胞肺癌（NSCLC）的疗效与毒性特征，但完整的毒性谱仍未明确。本研究依托美国食品药品监督管理局不良事件报告系统（FDA Adverse Event Reporting System）数据库，开展了一项全面的药物警戒分析，重点识别并表征非小细胞肺癌患者联合使用EGFR-TKIs与抗血管生成抑制剂相关的不良事件（AEs）。研究发现该联合疗法相关不良事件存在显著的发生特征，主要累及全身性疾病、皮肤及皮下组织病症与血管疾病。常见报告的不良事件包括皮疹、腹泻、乏力、恶心、食欲减退及贫血。值得注意的是，相较于单独使用EGFR-TKIs，该联合疗法可使多器官系统不良事件的发生率升高，且部分不良事件，如贫血、心律失常（arrhythmia）及溃疡性角膜炎（ulcerative keratitis），在部分患者中持续时长超过一年。非小细胞肺癌治疗中EGFR-TKIs与抗血管生成抑制剂的联合方案，呈现出独特且显著的不良事件特征，且不良事件往往存在延迟发作的特点。上述研究结果表明，亟需建立严格且持续的监测方案，以降低潜在长期不良事件的发生风险。