265O Anlotinib in locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma: A randomized, double-blind, multicenter phase II trial

Anlotinib is a novel multikinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This study investigated the potency of anlotinib in treating locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC). This is a randomized, double-blind, placebo-controlled, multicenter phase II trial (NCT02586337). Eligible pts were 18-70 years old with measurable, pathologically confirmed locally advanced or metastatic RAIR-DTC. Pts who had received previous anlotinib or other VEGFR-TKIs were excluded. Pts were randomized in a 2:1 ratio to receive anlotinib or placebo with a dose of 12mg QD for 2 weeks followed by a week of rest (2/1 schedule). The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Pts in placebo arm were allowed to receive open-label anlotinib after disease progression. Between September 2015 and August 2018, 113 pts (76 in anlotinib arm and 37 in placebo arm) were enrolled. The data cutoff date for primary endpoint was January 1, 2020. The research met its primary endpoint that the median PFS was 40.54 months (95% CI 28.29, NE) in anlotinib arm and 8.38 months (95% CI 5.59, 13.80) in placebo arm (p < 0.0001). The HR was 0.21 (95% CI 0.12, 0.37). The ORR was 59.21% in anlotinib arm and no response was observed in placebo arm (p < 0.0001). In addition, significant DCR benefit was observed for anlotinib treatment (anlotinib arm vs. placebo arm = 97.37% vs. 78.38%, p = 0.002). The OS data was still in follow-up. All pts in anlotinib arm and 97.30% pts in placebo arm experienced adverse events (p = 0.327). The incidence of treatment-related AEs of two groups was 100.00% and 86.49% (p = 0.003). Serious treatment-related AEs occurred in 15.79% pts received anlotinib. The most common AEs in anlotinib arm were hypertension (84.21%) and hypertriglyceridemia (68.42%). The study demonstrates the efficacy and safety of anlotinib and supports its use as a new option for the treatment of locally advanced or metastatic RAIR-DTC.