Anlotinib in metastatic renal cell carcinoma (mRCC) with a previous anti-VEGFR TKI: Preliminary results from a multicenter, phase II trial.

e16082 Background: Fibroblast growth factor (FGF) signaling regulates tumor growth and vascularization and partly mediates antiangiogenic escape from VEGFR inhibitors. Sequential TKI treatment has been proved to be effective in some patients with mRCC failed with a previous TKI. Anlotinib is a potent oral, small molecular TKI with a favorable safety profile in phase I trial which mainly targets VEGFR1/2/3, FGFR2. This multicenter phase II trial (NCT02072044) evaluated the efficacy of anlotinib in mRCC patients with clear cell being the predominant component who failed with a previous anti-VEGFR TKI. Methods: Patients who progressed on or were intolerant to sorafenib or sunitinib were enrolled. Anlotinib was administered orally at dose of 12 mg daily for 2 weeks followed by 1 week rest. The primary endpoint was PFS. Secondary end points included OS, ORR, safety. Results: Of 43 patients enrolled, 1 patient withdrawn his informed consent before treatment started. Of 42 patients received anlotinib, 30 patients had disease progression on and 10 were intolerant to previous sofafenib or sunitinib treatment. Data cutoff was May 15, 2015. Median PFS was 11.8 (95% CI, 8.5- ) months for the whole group, while 8.5 (95% CI, 4.4- ) months for those progressed on previous TKI treatment, not reached for those intolerant to previous TKI treatment. Overall response rate (ORR) for intent-to-treatment patients (ITT) was 19.1% (95%CI, 8.60-34.12). 6-week disease control rate was 90.5% (95%CI, 77.4%-97.3%). The most frequently reported treatment-related adverse events of all grades included hypertension 45.2%, hand-foot skin reaction 42.9%, fatigue 35.7%, proteinuria 35.7%, anorexia 33.3%, hypothyroidism 28.6%, hoarseness 23.8%, hypertriglyceridemia 21.3%, hypercholesterolemia 21.4%, oral mucositis 21.4%, skin rash 21.4%, thrombocytopenia 14.3%. The most common grade 3 or 4 side effects included lymphopenia 7.1%, hypertension 4.8% and hypothyroidism 4.8%. Conclusions: Anlotinib was preliminary shown to have promising efficacy with a favourable toxicity profile for patients with metastatic RCC who failed with previous sorafenib or sunitinib. Clinical trial information: NCT02072044.