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

Clin Cancer Res. 2021 Jul 1;27(13):3567-3575. doi: 10.1158/1078-0432.CCR-20-2950. Epub 2021 Apr 8.


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 and 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 (12 mg 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 endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS).

Results: Ninety-one patients were enrolled. At data cutoff date, the median PFS was significantly prolonged in the anlotinib group than in the placebo group (20.7 months vs. 11.1 months, P = 0.029; HR, 0.53; 95% confidence interval, 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 the anlotinib and placebo groups, respectively. The most common TRAEs of all grades in the anlotinib group were palmar-plantar erythrodysesthesia syndrome (62.9%), proteinuria (61.3%), and hypertriglyceridemia (48.4%).

Conclusions: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Neuroendocrine* / drug therapy
  • Double-Blind Method
  • Humans
  • Indoles
  • Quinolines
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / pathology


  • Indoles
  • Quinolines
  • anlotinib

Supplementary concepts

  • Thyroid cancer, medullary