{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:05:09Z","timestamp":1778875509798,"version":"3.51.4"},"reference-count":68,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Tyrosine kinase inhibitors (TKIs) are widely used in gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the reporting frequency of neuropsychiatric adverse drug reactions (ADRs) for TKIs through the analysis of European individual case safety reports (ICSRs). All ICSRs collected in EudraVigilance up to 31 December 2021 with one TKI having GISTs as an indication (imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP)) were included. A disproportionality analysis was performed to assess the frequency of reporting for each TKI compared to all other TKIs. The number of analyzed ICSRs was 8512, of which 57.9% were related to IM. Neuropsychiatric ADRs were reported at least once in 1511 ICSRs (17.8%). A higher reporting probability of neuropsychiatric ADRs was shown for AVA. Most neuropsychiatric ADRs were known, except for a higher frequency of lumbar spinal cord and nerve root disorders (reporting odds ratio, ROR 4.46; confidence interval, CI 95% 1.58\u201312.54), olfactory nerve disorders (8.02; 2.44\u201326.33), and hallucinations (22.96; 8.45\u201362.36) for AVA. The analyses of European ICSRs largely confirmed the safety profiles of TKIs in GISTs, but some ADRs are worthy of discussion. Further studies are needed to increase the knowledge of the neuropsychiatric disorders of newly approved TKIs.<\/jats:p>","DOI":"10.3390\/cancers15061851","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T03:09:37Z","timestamp":1679281777000},"page":"1851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-4696","authenticated-orcid":false,"given":"Maria Antonietta","family":"Barbieri","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela Elisa","family":"Sorbara","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8345-8679","authenticated-orcid":false,"given":"Giuseppe","family":"Cicala","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tindara","family":"Franchina","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariacarmela","family":"Santarpia","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Silvestris","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adulthood and Childhood Gaetano Barresi, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2509-7449","authenticated-orcid":false,"given":"Edoardo","family":"Spina","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1200\/EDBK_351231","article-title":"The GIST of Advances in Treatment of Advanced Gastrointestinal Stromal Tumor","volume":"42","author":"Schaefer","year":"2022","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.annonc.2021.09.005","article-title":"Gastrointestinal stromal tumours: ESMO\u2013EURACAN\u2013GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"33","author":"Casali","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nrc3143","article-title":"Gastrointestinal stromal tumours: Origin and molecular oncology","volume":"11","author":"Corless","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.21037\/gist-21-6","article-title":"New molecularly targeted drugs for gist after imatinib, sunitinib and regorafenib: A narrative review","volume":"5","author":"Mazzocca","year":"2022","journal-title":"Gastrointest. Stromal Tumor"},{"key":"ref_5","unstructured":"European Medicines Agency (2022, December 20). Glivec\u00ae, Summary of Product Characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/glivec-epar-product-information_en.pdf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6112","DOI":"10.1021\/acs.orglett.9b02259","article-title":"Modular Continuous Flow Synthesis of Imatinib and Analogues","volume":"21","author":"Fu","year":"2019","journal-title":"Org. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e184060","DOI":"10.1001\/jamaoncol.2018.4060","article-title":"Efficacy and Tolerability of 5-Year Adjuvant Imatinib Treatment for Patients with Resected Intermediate- or High-Risk Primary Gastrointestinal Stromal Tumor","volume":"4","author":"Raut","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"927587","DOI":"10.3389\/fonc.2022.927587","article-title":"An overview of agents and treatments for PDGFRA-mutated gastrointestinal stromal tumors","volume":"12","author":"Sun","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_9","unstructured":"European Medicines Agency (2022, December 20). Sutent\u00ae, Summary of Product Characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/sutent-epar-product-information_en.pdf."},{"key":"ref_10","unstructured":"European Medicines Agency (2023, January 19). Stivarga\u00ae, Summary of Product Characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/stivarga-epar-product-information_en.pdf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13569-019-0123-4","article-title":"Toxicity management of regorafenib in patients with gastro-intestinal stromal tumour (GIST) in a tertiary cancer centre","volume":"10","author":"Chamberlain","year":"2020","journal-title":"Clin. Sarcoma Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1007\/s11030-022-10406-8","article-title":"A patent review on efficient strategies for the total synthesis of pazopanib, regorafenib and lenvatinib as novel anti-angiogenesis receptor tyrosine kinase inhibitors for cancer therapy","volume":"26","author":"Shiri","year":"2022","journal-title":"Mol. Divers."},{"key":"ref_13","unstructured":"European Medicines Agency (2023, January 19). Qinlock\u00ae, Summary of Product Characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/qinlock-epar-product-information_en.pdf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105011","DOI":"10.1016\/j.bioorg.2021.105011","article-title":"The synthesis review of the approved tyrosine kinase inhibitors for anticancer therapy in 2015\u20132020","volume":"113","author":"Liang","year":"2021","journal-title":"Bioorg. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"175628482110081","DOI":"10.1177\/17562848211008177","article-title":"Ripretinib for the treatment of advanced gastrointestinal stromal tumor","volume":"14","author":"Zalcberg","year":"2021","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s10637-010-9593-1","article-title":"Sunitinib as a second-line therapy for advanced GISTs after failure of imatinib: Relationship between efficacy and tumor genotype in Korean patients","volume":"30","author":"Yoon","year":"2012","journal-title":"Investig. New Drugs"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"672500","DOI":"10.3389\/fonc.2021.672500","article-title":"Early and Next-Generation KIT\/PDGFRA Kinase Inhibitors and the Future of Treatment for Advanced Gastrointestinal Stromal Tumor","volume":"11","author":"Bauer","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_18","unstructured":"European Medicines Agency (2022, December 20). Ayvakit\u00ae, Summary of Product Characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/ayvakyt-epar-product-information_en.pdf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100159","DOI":"10.1016\/j.esmoop.2021.100159","article-title":"The EMA assessment of avapritinib in the treatment of gastrointestinal stromal tumours harbouring the PDGFRA D842V mutation","volume":"6","author":"Delgado","year":"2021","journal-title":"ESMO Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1002\/cncr.33630","article-title":"An updated review of the treatment landscape for advanced gastrointestinal stromal tumors","volume":"127","author":"Patel","year":"2021","journal-title":"Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1158\/1535-7163.MCT-18-0498","article-title":"Association of Imatinib Plasma Concentration and Single-nucleotide Polymorphisms with Adverse Drug Reactions in Patients with Gastrointestinal Stromal Tumors","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chang, Y.-R., Huang, W.-K., Wang, S.-Y., Wu, C.-E., Chen, J.-S., and Yeh, C.-N. (2021). A Nomogram Predicting Progression Free Survival in Patients with Gastrointestinal Stromal Tumor Receiving Sunitinib: Incorporating Pre-Treatment and Post-Treatment Parameters. Cancers, 13.","DOI":"10.3390\/cancers13112587"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e639","DOI":"10.1002\/onco.13674","article-title":"Avapritinib in Patients With Advanced Gastrointestinal Stromal Tumors Following at Least Three Prior Lines of Therapy","volume":"26","author":"George","year":"2021","journal-title":"Oncologist"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100222","DOI":"10.1016\/j.esmoop.2021.100222","article-title":"Standard versus personalized schedule of regorafenib in metastatic gastrointestinal stromal tumors: A retrospective, multicenter, real-world study","volume":"6","author":"Nannini","year":"2021","journal-title":"ESMO Open"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"175883592098649","DOI":"10.1177\/1758835920986498","article-title":"Ripretinib in gastrointestinal stromal tumor: The long-awaited step forward","volume":"13","author":"Valverde","year":"2021","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1038\/s41591-021-01538-9","article-title":"Safety and efficacy of avapritinib in advanced systemic mastocytosis: The phase 1 EXPLORER trial","volume":"27","author":"DeAngelo","year":"2021","journal-title":"Nat. Med."},{"key":"ref_27","unstructured":"European Medicines Agency (2022, December 06). Summary of Risk Management Plan for AYVAKYT (Avapritinib). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/rmp-summary\/saphnelo-epar-risk-management-plan-summary_en.pdf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100570","DOI":"10.1016\/j.bbih.2022.100570","article-title":"Abrupt onset of severe parkinsonism in a patient with metastatic gastrointestinal stromal tumor receiving treatment with avapritinib: A case report","volume":"27","author":"Drom","year":"2023","journal-title":"Brain Behav. Immun.\u2014Health"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rastogi, S., Kalaiselvan, V., Bin Jardan, Y.A., Zameer, S., and Sarwat, M. (2022). Comparative Study of Adverse Drug Reactions Associated with Filgrastim and Pegfilgrastim Using the EudraVigilance Database. Biology, 11.","DOI":"10.3390\/biology11020340"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rafaniello, C., Ferrajolo, C., Sullo, M.G., Gaio, M., Zinzi, A., Scavone, C., Gargano, F., Coscioni, E., Rossi, F., and Capuano, A. (2021). Cardiac events potentially associated to remdesivir: An analysis from the european spontaneous adverse event reporting system. Pharmaceuticals, 14.","DOI":"10.3390\/ph14070611"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s40264-020-01021-3","article-title":"PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database","volume":"44","author":"Zinzi","year":"2021","journal-title":"Drug Saf."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s40264-021-01086-8","article-title":"Immune Checkpoint Inhibitors and Cardiotoxicity: An Analysis of Spontaneous Reports in Eudravigilance","volume":"44","author":"Mascolo","year":"2021","journal-title":"Drug Saf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.jgo.2018.03.009","article-title":"Treatment outcomes in older patients with advanced gastrointestinal stromal tumor (GIST)","volume":"9","author":"Rutkowski","year":"2018","journal-title":"J. Geriatr. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/S0140-6736(06)69446-4","article-title":"Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: A randomised controlled trial","volume":"368","author":"Demetri","year":"2006","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0140-6736(12)61857-1","article-title":"Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): An international, multicentre, randomised, placebo-controlled, phase 3 trial","volume":"381","author":"Demetri","year":"2013","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/S1470-2045(20)30269-2","article-title":"Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): A multicentre, open-label, phase 1 trial","volume":"21","author":"Heinrich","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.critrevonc.2019.03.007","article-title":"Risk of fatal adverse events in cancer patients treated with sunitinib","volume":"137","author":"Zhao","year":"2019","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/cncr.28972","article-title":"Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway","volume":"121","author":"Hamnvik","year":"2015","journal-title":"Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1002\/cncr.26491","article-title":"Association of VEGF and VEGFR2 single nucleotide polymorphisms with hypertension and clinical outcome in metastatic clear cell renal cell carcinoma patients treated with sunitinib","volume":"118","author":"Kim","year":"2012","journal-title":"Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"84102","DOI":"10.18632\/oncotarget.21106","article-title":"Incidence and risk of regorafenib-induced hepatotoxicity","volume":"8","author":"Zhao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Seidel, C., Fenner, M., L\u00e4nger, F., Bantel, H., Ganser, A., and Gr\u00fcnwald, V. (2012). Imatinib-induced liver cirrhosis in a patient with advanced gastrointestinal stroma tumor (GIST). BMC Cancer, 12.","DOI":"10.1186\/1471-2407-12-186"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e39229","DOI":"10.2196\/39229","article-title":"Photosensitivity From Avapritinib: Pharamacovigilance Analysis","volume":"5","author":"Venkatakrishnan","year":"2022","journal-title":"JMIR Dermatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/bju.12940","article-title":"Sunitinib-induced hypertension, neutropaenia and thrombocytopaenia as predictors of good prognosis in patients with metastatic renal cell carcinoma","volume":"117","author":"Rautiola","year":"2016","journal-title":"BJU Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"55","DOI":"10.4103\/0022-3859.194227","article-title":"Imatinib-induced pleural effusion: A case report","volume":"63","author":"Banka","year":"2017","journal-title":"J. Postgrad. Med."},{"key":"ref_45","unstructured":"BC Cancer Agency (2023, January 19). BC Cancer Drug Manual Ripretinib. Available online: http:\/\/www.bccancer.bc.ca\/drug-database-site\/DrugIndex\/Ripretinib_handout.pdf."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"C077","DOI":"10.1158\/1535-7163.TARG-19-C077","article-title":"Abstract C077: Updated results of phase 1 study of ripretinib (DCC-2618), a broad-spectrum KIT and PDGFRA inhibitor, in patients with gastrointestinal stromal tumor (GIST) by line of therapy (NCT02571036)","volume":"18","author":"Chi","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e622","DOI":"10.1002\/onco.13632","article-title":"Optimal Avapritinib Treatment Strategies for Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors","volume":"26","author":"Joseph","year":"2021","journal-title":"Oncologist"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.cger.2013.07.002","article-title":"Normal Cognitive Aging","volume":"29","author":"Harada","year":"2013","journal-title":"Clin. Geriatr. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ejca.2020.12.008","article-title":"Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial","volume":"145","author":"Jones","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.ejpn.2019.03.001","article-title":"Clinical and genetic spectrum of SCN2A-associated episodic ataxia","volume":"23","author":"Schwarz","year":"2019","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5078","DOI":"10.1158\/1078-0432.CCR-20-1706","article-title":"Gastrointestinal Stromal Tumor: Challenges and Opportunities for a New Decade","volume":"26","author":"Serrano","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"187-e114","DOI":"10.1093\/oncolo\/oyac242","article-title":"Efficacy and Safety of Avapritinib in Treating Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Phase I\/II, Open-Label, Multicenter Study","volume":"28","author":"Li","year":"2023","journal-title":"Oncologist"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/dmd.121.000401","article-title":"Pharmacokinetic Drug-Drug Interactions with Drugs Approved by the US Food and Drug Administration in 2020: Mechanistic Understanding and Clinical Recommendations","volume":"50","author":"Yu","year":"2022","journal-title":"Drug Metab. Dispos."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"v399","DOI":"10.1093\/annonc\/mdx375.014","article-title":"Tyrosine kinase inhibitors (TKI): Awareness of drug-drug interaction","volume":"28","author":"Ozdemir","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_55","unstructured":"US Food and Drug Administration (2023, February 01). FDA Adverse Event Reporting System (FAERS) Public Dashboard, Available online: https:\/\/fis.fda.gov\/sense\/app\/95239e26-e0be-42d9-a960-9a5f7f1c25ee\/sheet\/7a47a261-d58b-4203-a8aa-6d3021737452\/state\/analysis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1007\/s00520-021-06658-z","article-title":"Taste, smell and mouthfeel disturbances in patients with gastrointestinal stromal tumors treated with tyrosine-kinase inhibitors","volume":"30","author":"IJzerman","year":"2022","journal-title":"Support. Care Cancer"},{"key":"ref_57","unstructured":"Food and Drug Administration (2023, January 24). Multi-Disciplinary Review and Evaluation NDA 212608 AYVAKIT (Avapritinib), Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2020\/212608Orig1s000MultidisciplineR.pdf."},{"key":"ref_58","first-page":"127","article-title":"The role of vascular endothelial growth factor in ischemic stroke","volume":"76","author":"Chen","year":"2021","journal-title":"Pharmazie"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Zuo, P.-Y., Chen, X.-L., Liu, Y.-W., Xiao, C.-L., and Liu, C.-Y. (2014). Increased Risk of Cerebrovascular Events in Patients with Cancer Treated with Bevacizumab: A Meta-Analysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102484"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Strom, B.L., Kimmel, S.E., and Hennessy, S. (2019). Pharmacoepidemiology, Wiley-Blackwell. [6th ed.].","DOI":"10.1002\/9781119413431"},{"key":"ref_61","unstructured":"Raschi, E., Moretti, U., Salvo, F., Pariente, A., Cosimo Antonazzo, I., De Ponti, F., and Poluzzi, E. (2019). Pharmacovigilance, IntechOpen."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e13484","DOI":"10.1111\/ecc.13484","article-title":"Quality of life of GIST patients with and without current tyrosine kinase inhibitor treatment: Cross-sectional results of a German multicentre observational study (PROSa)","volume":"30","author":"Eichler","year":"2021","journal-title":"Eur. J. Cancer Care"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1005626","DOI":"10.3389\/fonc.2022.1005626","article-title":"Safety profile of tyrosine kinase inhibitors used in non-small-cell lung cancer: An analysis from the Italian pharmacovigilance database","volume":"12","author":"Barbieri","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s40801-021-00278-z","article-title":"Adverse Drug Reactions with HER2-Positive Breast Cancer Treatment: An Analysis from the Italian Pharmacovigilance Database","volume":"9","author":"Barbieri","year":"2022","journal-title":"Drugs\u2014Real World Outcomes"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s40264-012-0014-6","article-title":"WHO strategy for collecting safety data in public health programmes: Complementing spontaneous reporting systems","volume":"36","author":"Pal","year":"2013","journal-title":"Drug Saf."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.3389\/fphar.2019.01161","article-title":"Ototoxic Adverse Drug Reactions: A Disproportionality Analysis Using the Italian Spontaneous Reporting Database","volume":"10","author":"Barbieri","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"858279","DOI":"10.3389\/fphar.2022.858279","article-title":"Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor-Associated Cardiotoxicity: A Recent Five-Year Pharmacovigilance Study","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4803","DOI":"10.1038\/s41598-020-61571-5","article-title":"Safety Profile of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Disproportionality Analysis of FDA Adverse Event Reporting System","volume":"10","author":"Huang","year":"2020","journal-title":"Sci. Rep."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/6\/1851\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:59:00Z","timestamp":1760122740000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/6\/1851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,20]]},"references-count":68,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["cancers15061851"],"URL":"https:\/\/doi.org\/10.3390\/cancers15061851","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742589334.793599755","asserted-by":"object"}]},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,20]]}}}