Adverse Event Signals for Osimertinib-Induced Muscle Toxicity Based on FAERS Database

doi:10.19803/j.1672-8629.20240587

Abstract

Abstract: Objective To analyze adverse event (AE) signals related to osimertinib-induced muscle toxicity so as to provide a reference for safe clinical use of this drug. Methods All the data on AE related to osimertinib and collected between the 4th quarter of 2015 and the 4th quarter of 2023 was retrieved from the FDA Adverse Event Reporting System (FAERS) database. Data mining of positive signals of AE related to osimertinib-induced muscle toxicity was performed using the reporting odds ratio (ROR) method and the proportional reporting ratio (PRR) method. Results A total of 616 AE related to muscle toxicity were reported, with osimertinib as the primary suspect (PS). The male-to-female ratio was 2.87. Muscle spasms and myositis met the criteria for positive signals based on both ROR and PRR. Conclusion In clinical use of osimertinib, adverse reactions mentioned in drug instructions, the risk of muscle toxicity and gender differences deserve attention. It is recommended that key indicators be monitored within 30 days of medications with osimertinib to ensure the safety of patients.

Key words: FDA Adverse Event Reporting System(FAERS), Osimertinib, Muscle Toxicity, Myositis, Myalgia, Creatine Kinase, Adverse Drug Events

CLC Number:

CHEN Lingbin, HUANG Zhixiong, ZHENG Cailin, WU Jinneng, CHEN Zhou. Adverse Event Signals for Osimertinib-Induced Muscle Toxicity Based on FAERS Database[J]. Chinese Journal of Pharmacovigilance, 2025, 22(4): 447-451.

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URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20240587

https://zgywjj.magtechjournal.com/EN/Y2025/V22/I4/447

References

[1] CDC, Lung Cancer Statistics, Center. Disease Control Prevent[EB/OL]. (2024-01-29)[2024-08-02]. https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html.
[2] ETTINGER DS, WOOD DE, AISNER DL, et al.Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology[J]. Journal of the National Comprehensive Cancer Network, 2022, 20(5): 497-530.
[3] DAS D, XIE L, HONG J. Next-Generation EGFR Tyrosine Kinase Inhibitors to Overcome C797S Mutation in Non-Small Cell Lung Cancer(2019-2024)[J/OL]. RSC Medicinal Chemistry,(2024-08-30)[2024-09-05]. https://doi.org/10.1039/d4md00384e.
[4] FDA. Tagrisso PackageInsert(USA)[EB/OL].[2024-08-02].https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208065s-008lbl.pdf.
[5] PARAFIANOWICZ P, KRISHAN R, BEUTLER BD, et al.Myositis-A Common but under Reported Adverse Effect of Osimertinib: Case Series and Revie w of the Literature[J]. Cancer Treatment and Research Communications, 2020, 25: 100254.
[6] LI Y, LIU Y, ZHAO Z, et al.Rhabdomyolysis in a Patient with Advanced Lung Cancer Treated with Osimertinib: a Case Report[J]. Translational Lung Cancer Research, 2023,12(3): 629-636.
[7] FUJIOKA S, KITAJIMA T, ITOTANI R.Myositis in a Patient with Advanced Lung Cancer Treated with Osimertinib[J]. Journal of Thoracic Oncology, 2018, 13(8): e137-e139.
[8] CHEN C, WU B, ZHANG C, et al.Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors: an Updated Comprehensive Disproportionality Analysis of the FDA Adverse Event Reporting System[J]. International Immunopharmacology, 2021, 95: 107498.
[9] LIU L, CHEN J, WANG L, et al.Association between Different GLP-1 Receptor Agonists and Gastrointestinal Adverse Reactions: a Real-World Disproportionality Study Based on FDA Adverse Event Reporting System Database[J]. Front Endocrinol (Lausanne), 2022, 13: 1043789.
[10] ZHOU C, PENG S, LIN A, et al.Psychiatric Disorders Associated with Immune Checkpoint Inhibitors: a Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS) database[J]. eClinical Medicine, 2023, 59: 101967.
[11] FUSAROLI M, SALVO F, BEGAUD B, et al.The Reporting of a Disproportionality Analysis for Drug Safety Signal Detection Using Individual Case Safety Reports in Pharmacovigilance (READUS-PV): Explanation and Elaboration[J]. Drug Safety, 2024, 47(6): 585-599.
[12] YIN Y, SHU Y, ZHU J, et al.A Real-World Pharmacovigilance Study of FDA Adverse Event Reporting System (FAERS) Events for Osimertinib[J]. Scientific Reports, 2022, 12(1): 19555.
[13] LI Z, ZOU W, YUAN J, et al.Gender Differences in Adverse Events Related to Osimertinib: a Real-World Pharmacovigilance Analysis of FDA Adverse Event Reporting System[J]. Expert Opinion on Drug Safety, 2024, 23(6): 763-770.
[14] ANAND K, ENSOR J, TRACHTENBERG B, et al.Osimertinib-Induced Cardiotoxicity: A Retrospective Review of the FDA Adverse Events Reporting System (FAERS)[J]. JACC CardioOncol, 2019, 1(2): 172-178.
[15] LAM WK.Lung Cancer in Asian Women-the Environment and Genes[J]. Respirology, 2005, 10(4): 408-417.
[16] FINSTERER J, SCORZA FA.Mild Creatine Kinase Elevations Do Not Necessarily Reflect Rhabdomyolysis[J]. American Family Physician, 2021, 104(1): 6-7.
[17] GOSS G, TSAI CM, SHEPHERD FA, et al.Osimertinib for Pretreated EGFR Thr790Met-Positive Advanced Non-Small-Cell Lung Cancer (AURA2): a Multicentre, Open-Label, Single-Arm, Phase 2 Study[J]. The Lancet Oncology, 2016, 17(12): 1643-1652.
[18] RONG CT,ZHANG JT,LUO JJ,et al.Osimertinib-Induced Severe and Rare Increase in Creatine Kinase with Body Aches: a Case Report[J]. Central South Pharmacy(中南药学), 2023, 21(11): 3098-3100.
[19] CROWLEY F, FITZGERALD BG, BHARDWAJ AS, et al.Life-Threatening Myositis in a Patient with EGFR-Mutated NSCLC on Osimertinib: Case Report[J]. JTO Clinical and Research Reports, 2022, 3(1): 100260.
[20] SUGIMOTO H, MATSUMOTO S, TSUJI Y, et al.Elevated Serum Creatine Kinase Levels Due to Osimertinib: a Case Report and Review of the Literature[J]. Journal of Oncology Pharmacy Practice, 2022, 28(2): 489-494.
[21] SAKAMOTO T, SAITO Y, TAKEKUMA Y, et al.Gefitinib-induced Myositis: a Novel Case Report[J]. Yakugaku Zasshi, 2023, 143(7): 617-620.
[22] LEROY MC, PERROUD J, DARBELLAY B, et al.Epidermal Growth Factor Receptor Down-Regulation Triggers Human Myoblast Differentiation[J]. PLoS One, 2013, 8(8): e71770.
[23] HINARD V, BELIN D, KONIG S, et al.Initiation of Human Myoblast Differentiation via Dephosphorylation of Kir2.1 K+ Channels at Tyrosine 242[J]. Development, 2008, 135(5): 859-867.
[24] LEDUC-GAUDET JP, HUSSAIN S, BARREIRO E, et al.Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging[J]. International Journal of Molecular Sciences, 2021, 22(15): 8179.
[25] KIM MJ, FEBBRARO D, FARKONA S, et al.Distinct Roles of UVRAG and EGFR Signaling in Skeletal Muscle Homeostasis[J]. Molecular Metabolism, 2021, 47: 101185.
[26] BROOME SC, WHITFIELD J, KARAGOUNIS LG, et al.Mitochondria as Nutritional Targets to Maintain Muscle Health and Physical Function During Ageing[J]. Sports Medicine, 2024, 54(9): 2291-2309.
[27] BATISTA PP, PERRACINI MR, PEREIRA DS, et al.Can EWGSOP2 and SDOC Definitions of Sarcopenia Identify Functional Muscle Quality?[J]. Journal of Frailty, Sarcopenia and Falls, 2024, 9(3): 192-200.
[28] ZHOU W, TONG J, WEN Z, et al.Prevalence and Factors Associated with Dynapenia among Middle-Aged and Elderly People in Rural Southern China[J]. Preventive Medicine Reports, 2024, 38: 102630.