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非小细胞肺癌中EGFR-TKI联合疗法的间质性肺疾病风险研究进展
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Abstract:
非小细胞肺癌(NSCLC)患者中，表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)已成为一线治疗方案。但联合治疗时，间质性肺疾病(ILD)风险备受关注。单药治疗时，不同代际EGFR-TKI的ILD风险特征各异，第一代在亚洲人群风险较高，第三代与剂量、治疗阶段及患者基线肺功能状态关联。联合治疗中，免疫检查点抑制剂增加重度ILD发生率，抗血管生成药物或序贯放疗可降低风险。临床管理策略如风险分层、剂量调整及跨代换药等逐步完善，提升了ILD防控效率。未来需大规模前瞻性研究明确不同药物组合及治疗顺序对ILD风险的长期影响。本文旨在综述EGFR-TKI不同代际及联合治疗的ILD风险研究现状。
In patients with non-small cell lung cancer (NSCLC), epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become first-line therapeutic agents. However, the risk of interstitial lung disease (ILD) during combination therapies has attracted significant attention. For monotherapy, different generations of EGFR-TKIs exhibit distinct ILD risk profiles: first-generation drugs show higher risks in Asian populations, while third-generation agents demonstrate correlations with dosage, treatment phases, and patients’ baseline pulmonary function status. In combination therapies, immune checkpoint inhibitors increase the incidence of severe ILD, whereas anti-angiogenic agents or sequential radiotherapy may mitigate risks. The optimization of clinical management strategies—including risk stratification, dosage adjustments, and cross-generation drug substitution—has progressively enhanced ILD prevention and control. Future large-scale prospective studies are required to clarify the long-term impacts of various drug combinations and treatment sequences on ILD risk. This review aims to summarize current research on ILD risks associated with different EGFR-TKI generations and their combination therapies.
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