# LIBRETTO-531: selpercatinib versus cabozantinib or vandetanib in advanced RET-mutant medullary thyroid cancer

Source: https://onco.cc/key-papers/paper-libretto-531-nejm-2023/  
OnCo record `paper-libretto-531-nejm-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The selective RET inhibitor selpercatinib cut the risk of progression by more than 70 percent compared with the older multikinase drugs cabozantinib and vandetanib in RET-mutant medullary thyroid cancer, with fewer side effects.

## Summary

Phase 3 trial of 291 patients with progressive advanced RET-mutant medullary thyroid cancer randomised 2:1 to selpercatinib or physician's choice of cabozantinib or vandetanib.

Progression-free survival at 12 months was 86.8 versus 65.7 percent (hazard ratio 0.28), response 69.4 versus 38.8 percent, and treatment-failure-free survival also favoured selpercatinib; grade 3 or higher adverse events were 52.8 versus 76.3 percent.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2023
- DOI: 10.1056/NEJMoa2309719
- Authors: Hadoux J, Elisei R, Brose MS, et al.
- Findings: Twelve-month progression-free survival 86.8 percent vs 65.7 percent; hazard ratio 0.28.; Objective response 69.4 percent vs 38.8 percent.
- What it means: Selpercatinib is the first-line standard for advanced RET-mutant medullary thyroid cancer; RET testing at diagnosis is essential.
- Caveats: Overall survival data immature.; Open-label design.

## Sources

- N Engl J Med 2023: https://doi.org/10.1056/NEJMoa2309719
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37870969/

## Connected records

- cancers: [Medullary thyroid cancer](https://onco.cc/cancers/medullary-thyroid-cancer/)
- drugs: [Selpercatinib](https://onco.cc/drugs/selpercatinib/)
- trials: [LIBRETTO-531](https://onco.cc/trials/libretto-531/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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