Anlotinib in Locally Advanced or Metastatic Medullary Thyroid Carcinoma: A Randomized, Double-Blind Phase IIB Trial.

Purpose: Medullary thyroid cancer (MTC) accounts for about 2% of all thyroid cancer, but has a relatively poor prognosis compared with differentiated thyroid cancer. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR and c-Kit. This multicenter, randomized, double-blind, placebo-controlled phase ⅡB study (ALTER 01031, NCT02586350) was conducted to investigate the efficacy and safety of anlotinib in MTC. Patients and Methods: Patients with histopathologically confirmed, unresectable locally advanced or metastatic MTC were enrolled and randomly assigned in a 2:1 ratio to receive anlotinib (12mg once daily from day 1 to 14 every 3 weeks) or placebo. Patients in placebo group were allowed to receive open-label anlotinib after disease progression. The primary end point was progression-free survival (PFS); secondary end points included objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Results: 91 patients were enrolled. At data cutoff date, the median PFS was significantly prolonged in anlotinib group than in placebo group (20.7 months vs. 11.1 months, P = 0.029, HR = 0.53 [95% CI, 0.30-0.95]). The ORR of anlotinib treatment was 48.4%. The incidence of treatment related adverse events (TRAE) was 100% and 89.7% in anlotinib and placebo groups. The most common TRAE of all grades in the anlotinib group were palmar-plantar erythrodysesthesia syndrome (62.9%), proteinuria (61.3%) and hypertriglyceridemia (48.4%). Conclusion: Anlotinib demonstrates its efficacy and safety in this phase ⅡB trial for the treatment of MTC and may become a new choice for this rare disease, especially for Chinese patients.