Safety assessment of KRAS (G12C) inhibitors based on the FDA Adverse Event Reporting System (FAERS) database: A real-world pharmacovigilance study

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2024-10-01 DOI:10.1016/j.lungcan.2024.107966

Maohua Chen , Yaping Huang , Shaojun Jiang , Chengjie Ke

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引用次数: 0

Abstract

Objectives

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.

Materials and methods

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).

Results

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).

Conclusion

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.

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基于 FDA 不良事件报告系统 (FAERS) 数据库的 KRAS (G12C) 抑制剂安全性评估：真实世界药物警戒研究。

目的：KRAS（G12C）抑制剂（sotorasib和adagrasib）已获准用于治疗KRAS（G12C）突变的非小细胞肺癌（NSCLC）患者。KRAS (G12C)抑制剂上市后的相关数据仍然有限，相关研究结果尚未得出支持KRAS (G12C)抑制剂长期安全性的确凿证据：这项调查采用先进的数据挖掘技术，利用美国食品药物管理局不良事件报告系统（FAERS），全面评估了KRAS（G12C）抑制剂引起的不良事件（AEs）。数据集涵盖 2021 年第一季度至 2024 年第一季度。为了量化 KRAS (G12C) 抑制剂与 AE 之间的相关性，我们进行了比例失调分析。评估比例失调的指标包括报告几率比（ROR）、比例报告比（PRR）、信息成分（IC）和经验贝叶斯几何平均数（EBGM）：共识别出2253份和486份与索托拉西布和阿达拉西布相关的报告，分别识别出51个和26个首选术语。索托拉西布最常见的不良反应包括腹泻（ROR 5.27）、肝毒性（ROR 38.09）、丙氨酸氨基转移酶升高（ROR 17.41）、天冬氨酸氨基转移酶升高（ROR 20.88）和肝功能异常（ROR 19.88）。阿达拉昔布最常见的不良反应包括腹泻（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）。与索拉西布相比，阿达拉西布发生肝毒性的风险相对较低，但发生严重AEs的风险较高（P 结论：阿达拉西布的肝毒性风险相对较低，但发生严重AEs的风险较高）：我们的研究结果将为医护人员识别 KRAS (G12C) 抑制剂相关的 AEs 以及索托拉西布和阿达拉西布之间的差异提供有价值的证据，并指导他们的临床实践。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.