| アブストラクト | BACKGROUND: Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are an essential therapeutic option in the management of various solid tumors, particularly renal cell carcinoma (RCC). However, post-marketing data regarding their potential cardiovascular toxicities are scant. OBJECTIVE: To identify and characterize cardiovascular adverse events (CVAEs) of VEGFR-TKIs indicated for RCC. PATIENTS AND METHODS: Disproportionality analysis of the US Food and Drug Administration adverse event reporting system (July 2014-December 2019) using the reporting odds ratio (ROR) and the lower bound of the Information component (IC) 95% credibility interval (IC025 > 0 is significant). RESULTS: We identified 51,836 adverse event reports of sunitinib, pazopanib, axitinib, cabozantinib, and lenvatinib in the full database [36% women; median age 65 years (range 57-73)]. CVAEs accounted for 11,784 (23%) of the reports, with hypertension [n = 5548 (11%), ROR = 6.55 (95% CI 6.37-6.74), IC025 = 2.48] and hemorrhages [n = 3710 (7.2%), ROR = 1.28 (1.24-1.32), IC025 = 0.28] being the most frequent types. Additional CVAEs were over-reported with VEGFR-TKIs treatment, including aortic dissection [n = 61 (0.1%), ROR = 3.50 (2.71-4.51)], pericardial diseases [n = 173 (0.3%), ROR = 1.98 (1.70-2.30)], cardiomyopathy [n = 61 (0.1%), ROR = 1.89 (1.47-2.43)], heart failure [n = 868 (1.7%), ROR = 1.35 (1.26-1.44)], and venous thromboembolism [n = 604 (1.2%), ROR = 1.33 (1.23-1.45), all IC025 > 0]. The major pericardial disorder was non-malignant pericardial effusion [n = 134 (77%)]. Aortic dissections were also over-reported in patients without concomitant elevated blood pressure [ROR = 2.68 (1.97-3.63), IC025 = 0.91]. Finally, CVAEs were reported more often following lenvatinib and sunitinib treatment compared to other VEGFR-TKIs. CONCLUSIONS: In post-marketing surveillance data, VEGFR-TKIs are associated with increased reporting of various CVAEs, including pericardial diseases, particularly non-malignant pericardial effusion, and aortic dissections. Moreover, VEGFR-TKIs differ in their CVAE reporting patterns. Clinicians should be conscious of these findings in the care of VEGFR-TKIs recipients. |
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| 投稿日 | 2021/5/11 |
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| 投稿者 | Goldman, Adam; Bomze, David; Dankner, Rachel; Fourey, Dana; Boursi, Ben; Arad, Michael; Maor, Elad |
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| ジャーナル名 | Targeted oncology |
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| 組織名 | Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel.;School of Medicine, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv,;Israel.;Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and;Health Policy Research, Sheba Medical Center, Ramat Gan, Israel.;Department of Epidemiology and Preventive Medicine, School of Public Health,;Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.;Department of Oncology, Sheba Medical Center, Ramat Gan, Israel.;Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania,;Philadelphia, PA, USA.;Elad.Maor@sheba.health.gov.il.;Israel. Elad.Maor@sheba.health.gov.il. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/33970401/ |
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