LBA88 - Anlotinib in locally advanced or metastatic radioiodine-refractory differentiated thyroid carcinoma: A randomized, double-blind, multicenter phase II trial

Background

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).

Methods

This is a randomized, double-blind, placebo-controlled, multicenter phase II trial (NCT02586337). Eligible pts were 18-70 years age, ECOG PS of 0-1 and diagnosed as having pathologically confirmed locally advanced or metastatic RAIR-DTC with at least one measurable lesion. Previous anlotinib or other VEGFR-TKIs were not allowed. Pts were randomized (2:1) to receive anlotinib or placebo (12mg QD for 2 weeks every 3 weeks). The primary endpoint was PFS. The secondary endpoints included ORR, DCR, OS, Quality of life and safety. Pts in placebo arm could receive open-label anlotinib after disease progression.

Results

Between September 2015 and August 2018, 113 pts (76 in anlotinib arm, 37 in placebo arm) were enrolled. The data cutoff date for primary endpoint was January 1, 2020. The research met its 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). OS data was immature while a trend of OS benefit could be observed (Not reached vs. 52.83 months; HR = 0.57 [95% CI 0.29, 1.12]; p = 0.0976). This prolongation in OS became significant (HR = 0.36 [95%CI 0.18, 0.73], P = 0.0033) when a potential bias from crossover (24 pts received open-label anlotinib) was adjusted with a two-stage estimation method. ORR was 59.21% in anlotinib arm and no response was observed in placebo arm (p < 0.0001). DCR was 97.37% versus 78.38% (p = 0.0019). 26 pts in anlotinib arm needed dose reduction. The incidence of treatment-related AEs (TRAEs) in anlotinib and placebo arms was 100.00% and 86.49%. Serious TRAEs occurred in 15.79% pts received anlotinib. The most common TRAEs in anlotinib arm were hypertension (84.21%) and hand-foot syndrome (73.68%).

Conclusions

This study demonstrates the efficacy and safety of anlotinib and supports its use as a new option in the treatment of locally advanced or metastatic RAIR-DTC.

Clinical trial identification

NCT02586337.

Editorial acknowledgement

Legal entity responsible for the study

Chia Tai TianQing Pharmaceutical Group Co., Ltd.

Funding

Chia Tai TianQing Pharmaceutical Group Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.