Treatment-Related Adverse Events of Combination EGFR Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitor in EGFR-Mutant Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.
Treatment-Related Adverse Events of Combination EGFR Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitor in EGFR-Mutant Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.
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表皮生长因子酪氨酸激酶抑制剂(EGFR-TKI)和免疫检查点抑制剂(ICI)在EGFR突变的晚期非小细胞肺癌(NSCLC)中的联合应用引起了人们对重叠毒性风险的担忧。尽管联合应用奥西美替尼和杜伐单抗的间质性肺部疾病的报告比例更高，但目前关于EGFR-TKI和ICI治疗相关不良事件(TRAE)的证据仍然仅限于肺炎和奥西美替尼的使用。这项系统性综述和荟萃分析调查了EGFR-TKI和ICI联合治疗是否与TKI单一治疗相比增加了总体和器官特异性TRAE的发生率。TKI和ICI联合应用时，高级别器官特异性TRAE的比例较高，包括皮肤、胃肠道不良事件和间质性肺部疾病。有必要进行进一步的前瞻性研究，以确定ICI的最佳药物选择，以及在EGFR-TKI失败后启动ICI的最佳时机。(1)背景：我们进行了一项荟萃分析，以检验联合使用表皮生长因子酪氨酸激酶抑制剂(EGFR-TKI)和免疫检查点抑制剂(ICI)是否会增加晚期非小细胞肺癌(NSCLC)的治疗相关不良事件(TRAE)。(2)方法：检索MEDLINE、EMBASE、Cochrane数据库中的文章。将EGFR-TKI和ICI联合治疗的总体和器官特异性TRAE的比例和优势比(OR)与TKI单一治疗进行比较。(3)结果：8篇研究符合我们的选择标准。任何级别的器官特异性TRAE在EGFR-TKI联合ICI组比TKI组更常见(皮肤：OR=1.19，p=0.012；胃肠道：OR=1.04，p=0.790；ILD：OR=1.28，p=0.001)。≥3级TRAE在联合治疗中也更常见(皮肤：OR=1.13，p=0.082；胃肠道：OR=1.13，p=0.076；ILD：OR=1.16，p=0.003)。(4)结论：≥3级皮肤及胃肠道TRAE和ILDs的比例明显高于单纯TKI。由于这一荟萃分析中包含的研究数量较少，因此在解释结果时必须谨慎。
The use of combination epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) and immune checkpoint inhibitor (ICI) in EGFR-mutant, advanced non-small cell lung cancer (NSCLC) has raised concerns over the risk of overlapping toxicities. Although a higher proportion of interstitial lung diseases was reported with the combination of osimertinib and durvalumab, the current evidence on the treatment-related adverse events (trAEs) of EGFR-TKI and ICI remains limited to pneumonitis and the use of osimertinib. This systematic review and meta-analysis investigates whether combination EGFR-TKI and ICI increases the incidence of overall and organ-specific trAEs compared to TKI monotherapy. A higher proportion of high-grade organ-specific trAEs was observed in combination TKI and ICI including skin, gastrointestinal adverse events, and interstitial lung diseases. Further prospective studies are warranted to determine the optimal drug of choice of ICI and the best timing of initiation of ICI after failure to prior EGFR-TKI. (1) Background: We performed a meta-analysis to examine whether combined epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) and immune checkpoint inhibitor (ICI) increases treatment-related adverse events (trAEs) in advanced non-small cell lung cancer (NSCLC). (2) Methods: Articles from MEDLINE, EMBASE, and Cochrane databases were searched. Proportions and odds ratios (ORs) of the pooled incidence of overall and organ-specific trAEs in combination EGFR-TKI and ICI were compared to TKI monotherapy. (3) Results: Eight studies fulfilled our selection criteria. Any-grade organ-specific trAEs were more common in combination EGFR-TKI and ICI than TKI monotherapy (skin: OR = 1.19, p = 0.012; gastrointestinal tract: OR = 1.04, p = 0.790; ILD: OR = 1.28, p = 0.001). Grade ≥ 3 trAEs were also more frequent in combination treatment (skin: OR = 1.13, p = 0.082; gastrointestinal tract: OR = 1.13, p = 0.076; ILD: OR = 1.16, p = 0.003). (4) Conclusions: A higher proportion of grade ≥3 skin and gastrointestinal trAEs and ILDs was observed in combination TKI and ICI compared to TKI alone. Caution has to be taken when interpreting the results owing to the small number of studies included in this meta-analysis.
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