Objective  To explore the risk signals associated with axitinib and to provide references for safe and rational clinical drug use.

Methods  Data on adverse event reports related to axitinib from the FAERS database from January 1, 2012 to June 30, 2024 were collected. Proportional reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods were used for data mining. The preferred system organ classification and preferred terms from the adverse drug reaction terminology set were used to classify and describe the mined risk signals.

Results  A total of 12 927 adverse event reports involving acitinib as the primary suspect drug were collected, including 8 428 male patients (65.2%) and 3 493 female patients (27.0%). A total of 63 positive signals were identified, with the most commonly reported systemic organ conditions being kidney and urinary system diseases, gastrointestinal disorders, and various tumors (including benign, malignant, and unspecified types, such as cysts and polyps). The new adverse events exhibiting strong signal intensity included diarrhea, progressive tumors, hypertension, oral mucositis, oral pain, and renal function impairment.

Conclusion  The adverse events associated with axitinib in the treatment of urinary system tumors significantly impact patients' quality of life and should be carefully considered in clinical practice to ensure patient safety.

1.Owens-Walton J, Williams C, Rompré-Brodeur A, et al. Minority enrollment in phase ii and iii clinical trials in urologic oncology[J]. J Clin Oncol, 2022, 40(14): 1583-1589. DOI: 10.1200/jco.21.01885.

2.Zhang Y, Chen J, Liu H, et al. The incidence of immune-related adverse events (irAEs) and their association with clinical outcomes in advanced renal cell carcinoma and urothelial carcinoma patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis[J]. Cancer Treat Rev, 2024, 129: 102787. DOI: 10.1016/j.ctrv.2024.102787.

3.Dai YN, Yu E, Zeegers MP, et al. The association between dietary inflammatory potential and urologic cancers: a Meta-analysis[J]. Adv Nutr, 2024, 15(1): 100124. DOI: 10.1016/j.advnut.2023.09.012.

4.Kumar R, Matulewicz R, Mari A, et al. Impact of smoking on urologic cancers: a snapshot of current evidence[J]. World J Urol, 2023, 41(6): 1473-1479. DOI: 10.1007/s00345-023-04406-y.

5.Cumberbatch MGK, Jubber I, Black PC, et al. Epidemiology of bladder cancer: a systematic review and contemporary update of risk factors in 2018[J]. Eur Urol, 2018, 74(6): 784-795. DOI: 10.1016/j.eururo.2018.09.001.

6.Kim AE, Lou KW, Giobbie-Hurder A, et al. Abnormal vascular structure and function within brain metastases is linked to pembrolizumab resistance[J]. Neuro Oncol, 2024, 26(5): 965-974. DOI: 10.1093/neuonc/noad236.

7.Naito H, Iba T, Takakura N. Mechanisms of new blood-vessel formation and proliferative heterogeneity of endothelial cells[J]. Int Immunol, 2020, 32(5): 295-305. DOI: 10.1093/intimm/dxaa008.

8.Roskoski R, Jr. Vascular endothelial growth factor (VEGF) and VEGF receptor inhibitors in the treatment of renal cell carcinomas[J]. Pharmacol Res, 2017, 120: 116-132. DOI: 10.1016/j.phrs.2017.03.010.

9.Hsieh JJ, Purdue MP, Signoretti S, et al. Renal cell carcinoma[J]. Nat Rev Dis Primers, 2017, 3: 17009. DOI: 10.1038/nrdp.2017.9.

10.LiverTox: clinical and research information on drug-induced liver injury [EB/OL]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012. https://pubmed.ncbi.nlm.nih.gov/31643176/.

11.Yamamoto Y, Tsunedomi R, Fujita Y, et al. Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma[J]. Oncotarget, 2018, 9(24): 17160-17170. DOI: 10.18632/oncotarget.24715.

12.Wang J, Zhang A, Ye M, et al. Examining the safety of mirabegron: an analysis of real-world pharmacovigilance data from the US FDA adverse event reporting system (FAERS) database[J]. Front Pharmacol, 2024, 15: 1376535. DOI: 10.3389/fphar.2024.1376535.

13.Zou F, Cui Z, Lou S, et al. Adverse drug events associated with linezolid administration: a real-world pharmacovigilance study from 2004 to 2023 using the FAERS database[J]. Front Pharmacol, 2024, 15: 1338902. DOI: 10.3389/fphar.2024.1338902.

14.Markowski MC, Boorjian SA, Burton JP, et al. The microbiome and genitourinary cancer: a collaborative review[J]. Eur Urol, 2019, 75(4): 637-646. DOI: 10.1016/j.eururo.2018.12.043.

15.Martin A, Woolbright BL, Umar S, et al. Bladder cancer, inflammageing and microbiomes[J]. Nat Rev Urol, 2022, 19(8): 495-509. DOI: 10.1038/s41585-022-00611-3.

16.Ma YH, Wang SY, Ren YP, et al. Antitumor effect of axitinib combined with dopamine and PK-PD modeling in the treatment of human breast cancer xenograft[J]. Acta Pharmacol Sin, 2019, 40(2): 243-256. DOI: 10.1038/s41401-018-0006-x.

17.Powles T, Plimack ER, Soulières D, et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2020, 21(12): 1563-1573. DOI: 10.1016/s1470-2045(20)30436-8.

18.Tomita Y, Motzer RJ, Choueiri TK, et al. Efficacy and safety of avelumab plus axitinib in elderly patients with advanced renal cell carcinoma: extended follow-up results from JAVELIN Renal 101[J]. ESMO Open, 2022, 7(2): 100450. DOI: 10.1016/j.esmoop.2022.100450.

19.白艳玉. 肾细胞癌的临床病理特征及其特异性生存影响因素分析[J]. 临床医药文献电子杂志, 2018, 5(54): 193. DOI: 10.16281/j.cnki.jocml.2018.54.162.

20.Schmidinger M, Danesi R, Jones R, et al. Individualized dosing with axitinib: rationale and practical guidance[J]. Future Oncol, 2018, 14(9): 861-875. DOI: 10.2217/fon-2017-0455.

21.Rini BI, Escudier B, Hariharan S, et al. Long-term safety with axitinib in previously treated patients with metastatic renal cell carcinoma[J]. Clin Genitourin Cancer, 2015, 13(6): 540-547. e77. DOI: 10.1016/j.clgc.2015.07.001.

22.Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma[J]. N Engl J Med, 2019, 380(12): 1116-1127. DOI: 10.1056/NEJMoa1816714.

23.Motzer RJ, Escudier B, Tomczak P, et al. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: overall survival analysis and updated results from a randomised phase 3 trial[J]. Lancet Oncol, 2013, 14(6): 552-562. DOI: 10.1016/s1470-2045(13)70093-7.