Anlotinib for Patients With mRCC Previously Treated With a VEGFR-TKI
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Anlotinib for Patients With Metastatic Renal Cell Carcinoma Previously Treated With One Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor: A Phase 2 Trial
Front Oncol 2020 Jun 01;10(xx)664, J Ma, Y Song, J Shou, Y Bai, H Li, X Xie, H Luo, X Ren, J Liu, D Ye, X Bai, C Fu, S Qin, J Wang, AP ZhouFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This was a single-arm, open-label, phase II trial of anlotinib, a multikinase inhibitor targeting VEGFR1/2/3, PDGFR, and FGFR in patients with mRCC who progressed after or were intolerant to sorafenib or sunitinib. Eligible patients were enrolled across 11 hospitals in China and had mRCC with a clear cell component to receive oral anlotinib daily 12 mg on days 1–14 every 3 weeks. The primary endpoint was PFS. Between 3/2014 and 3/2015, a total of 42 patients were enrolled, with a median age of 59; 85.7% had prior surgery, and 54.8% received prior sunitinib while the others received prior sorafenib. The median duration of treatment was 8.3 months, and the median PFS was 14.0 months. The median OS was 21.4 months for the whole population. In all, 7 patients (16.7%) achieved confirmed objective response and 28 (66.7%) had stable disease. For patients progressing after previous TKI, the objective response rate (ORR) and disease-control rate (DCR) were 15.6% and 78.1%; for patients who were intolerant to a previous TKI, the ORR and DCR were 20% and 100%, respectively. The most common grade 3 adverse events were elevated GGT (7.1%), hypothyroidism (4.8%), and hypertension (4.8%).
This study provides promising efficacy results in refractory mRCC with a relatively tolerable safety profile for anlotinib. Its uniqueness lies in its ability to strongly inhibit FGFR, which may represent a mechanism for escape or resistance to anti-angiogenesis inhibitors. Although the study size is fairly small, further exploration in larger prospective mRCC settings for anlotinib, particularly in combination with IO, may be warranted.