KRAS (G12C) 抑制剂（sotorasib 和 adagrasib）已被批准用于治疗 KRAS (G12C) 突变的非小细胞肺癌 (NSCLC) 患者。 KRAS（G12C）抑制剂的上市后数据仍然有限，相关研究结果尚未得出支持KRAS（G12C）抑制剂长期安全性确凿证据。本研究全面评估了归因于KRAS（G12C）抑制剂的不良事件（AE） KRAS (G12C) 抑制剂采用先进的数据挖掘技术，利用 FDA 不良事件报告系统 (FAERS)。该数据集涵盖从 2021 年第一季度到 2024 年第一季度的时期。进行了不成比例分析来量化 KRAS (G12C) 抑制剂和 AE 之间的相关性。用于评估不成比例性的指标包括报告比值比 (ROR)、比例报告比 (PRR)、信息分量 (IC) 和经验贝叶斯几何平均数 (EBGM)。 总共有 2,253 份和 486 份报告被评估。被确定为与 sotorasib 和 adagrasib 相关，分别确定了 51 个和 26 个首选术语。 sotorasib最常见的AE包括腹泻（ROR 5.27）、肝毒性（ROR 38.09）、丙氨酸转氨酶升高（ROR 17.41）、天冬氨酸转氨酶升高（ROR 20.88）和肝功能异常（ROR 19.88）。阿达格拉西最常见的 AE 包括腹泻 (ROR 4.21)、恶心 (ROR 3.84)、呕吐 (ROR 5.36)、食欲下降 (ROR 4.79) 和脱水 (ROR 7.00)。与 sotorasib 相比，adagrasib 的肝毒性风险相对降低，但严重 AE 的风险增加 (P < 0.001)。我们的研究结果将为医疗保健专业人员识别与 KRAS (G12C) 抑制剂相关的 AE 以及 sotorasib 和 adagrasib 之间的差异提供宝贵的证据，并指导他们的临床实践。版权所有 © 2024 Elsevier B.V. 保留所有权利。

KRAS (G12C) inhibitors (sotorasib and adagrasib) have approved treatment in patients with KRAS (G12C)-mutated non-small cell lung cancer (NSCLC). The post-marketing data concerning KRAS (G12C) inhibitors remain limited, and the outcomes of relevant studies are yet to yield conclusive evidence supporting the long-term safety of KRAS (G12C) inhibitors.This investigation comprehensively assessed adverse events (AEs) attributed to KRAS (G12C) inhibitors by employing advanced data mining techniques, utilizing the FDA Adverse Event Reporting System (FAERS). The dataset encompasses the period from the first quarter of 2021 to the first quarter of 2024. A disproportionality analysis was conducted to quantify the correlation between KRAS (G12C) inhibitors and AEs. The metrics employed for the evaluation of disproportionality comprise the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayesian geometric mean (EBGM).A total of 2,253 and 486 reports were identified as related to sotorasib and adagrasib, with the identification of 51 and 26 preferred terms, respectively. The most frequent AEs of sotorasib comprised diarrhoea (ROR 5.27), hepatotoxicity (ROR 38.09), alanine aminotransferase increased (ROR 17.41), aspartate aminotransferase increased (ROR 20.88), and hepatic function abnormal (ROR 19.88). The most common AEs of adagrasib included diarrhoea (ROR 4.21), nausea (ROR 3.84), vomiting (ROR 5.36), decreased appetite (ROR 4.79), and dehydration (ROR 7.00). A relatively reduced risk of hepatotoxicity but a increased risk of serious AEs in adagrasib compared to sotorasib (P < 0.001).Our findings would provide valued evidence for healthcare professionals to recognize AEs associated with KRAS (G12C) inhibitors and differences between sotorasib and adagrasib, and guide their clinical practice.Copyright © 2024 Elsevier B.V. All rights reserved.