LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-naïve RET-mutant medullary thyroid cancer

Future Oncol. 2022 Sep;18(28):3143-3150. doi: 10.2217/fon-2022-0657. Epub 2022 Aug 15.


Selpercatinib is a first-in-class, highly selective and potent, central nervous system-active RET kinase inhibitor. In the phase I/II trial, selpercatinib demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pre-treated and treatment-naive patients with RET-mutant medullary thyroid cancer (MTC). LIBRETTO-531 (NCT04211337) is a multicenter, open-label, randomized, controlled, phase III trial comparing selpercatinib to cabozantinib or vandetanib in patients with advanced/metastatic RET-mutant MTC. The primary objective is to compare progression-free survival (per RECIST 1.1) by blinded independent central review of patients with progressive, advanced, multikinase inhibitor-naive, RET-mutant MTC treated with selpercatinib versus cabozantinib or vandetanib. Key secondary objectives are to compare other efficacy outcomes (per RECIST 1.1) and tolerability of selpercatinib versus cabozantinib or vandetanib.

Keywords: RET alteration; RET kinase inhibitor; RET mutation; medullary thyroid cancer; phase III trial; selpercatinib; targeted therapy.

Plain language summary

Selpercatinib (also known by the brand name Retevmo®/Retsevmo®) is a new treatment available in multiple countries for people with advanced or metastatic RET-mutant medullary thyroid cancer (MTC). Thyroid cancer starts in your thyroid gland and may spread or metastasize to other parts of the body, including lungs, bones, and occasionally the brain, which means the cancer is likely to be advanced. Advanced thyroid cancer can be driven by a gene in your body, one of which is RET. This is a summary of the LIBRETTO-531 study which compares selpercatinib, which is a strong and selective inhibitor of RET, with two approved drugs, cabozantinib and vandetanib. Patients with advanced or metastatic RET-mutant MTC who have not already received treatment with kinase inhibitors are being enrolled. This trial will evaluate how long people during and after treatment live with the disease without it getting worse. Selpercatinib may affect both healthy cells and tumor cells, which can result in side effects, which will also be evaluated in this study. This study is active and currently recruiting new patients. Clinical Trial Registration: NCT04211337 (

Publication types

  • Review

MeSH terms

  • Anilides
  • Carcinoma, Neuroendocrine* / drug therapy
  • Carcinoma, Neuroendocrine* / genetics
  • Clinical Trials, Phase III as Topic
  • Humans
  • Multicenter Studies as Topic
  • Protein Kinase Inhibitors / adverse effects
  • Proto-Oncogene Proteins c-ret / genetics
  • Pyrazoles
  • Pyridines
  • Randomized Controlled Trials as Topic
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / genetics


  • Anilides
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • cabozantinib
  • selpercatinib
  • Proto-Oncogene Proteins c-ret
  • RET protein, human

Supplementary concepts

  • Thyroid cancer, medullary

Associated data