# LIBRETTO-531

Source: https://onco.cc/trials/libretto-531/  
OnCo record `libretto-531` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Showed that a drug built specifically for the RET mutation beats the older multi-target pills in medullary thyroid cancer, with far fewer side effects.

## Summary

LIBRETTO-531, trial NCT04211337 sponsored by Eli Lilly and reported in 2023, showed that a drug built specifically for the RET mutation beats the older multi-target tablets in untreated progressive RET-mutant medullary thyroid cancer, with far fewer side effects. It randomised 291 patients to selpercatinib or cabozantinib or vandetanib, met its primary progression-free survival endpoint with a large effect, improved treatment failure-free survival and roughly halved the rate of severe adverse events, the first randomised proof that RET-selective therapy should be first line. OnCo links it to thyroid cancer and multiple endocrine neoplasia syndromes, kinase inhibitors, RET as a target, selpercatinib, vandetanib, LIBRETTO-431 and Lori J. Wirth. Whether resistance to selective RET inhibition can be met by next-generation drugs is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT04211337
- Phase: 3
- Setting: Untreated progressive RET-mutant medullary thyroid cancer: selpercatinib vs cabozantinib or vandetanib
- Sponsor: Eli Lilly
- Enrolled: 291
- Result: PFS HR 0.28; 12-month PFS 86.8% vs 65.7%.
- Outcomes: Progression-free survival at 12 months: Selpercatinib 86.8% vs Cabozantinib or vandetanib 65.7%, HR 0.28
- Replication: Consistent with single-arm LIBRETTO-001 and with pralsetinib (ARROW) activity in RET-mutant MTC.

## Sources

- ClinicalTrials.gov NCT04211337: https://clinicaltrials.gov/study/NCT04211337
- NEJM 2023: https://www.nejm.org/doi/full/10.1056/NEJMoa2309719

## Connected records

- cancers: [Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)](https://onco.cc/cancers/multiple-endocrine-neoplasia/), [Multiple endocrine neoplasia type 2 (MEN2A and MEN2B)](https://onco.cc/cancers/men2-syndrome/), [Thyroid cancer](https://onco.cc/cancers/thyroid/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [RET](https://onco.cc/targets/ret/)
- drugs: [Selpercatinib](https://onco.cc/drugs/selpercatinib/), [Vandetanib](https://onco.cc/drugs/vandetanib/)
- companies: [Eli Lilly (incl. Loxo)](https://onco.cc/companies/eli-lilly/)
- trials: [LIBRETTO-431](https://onco.cc/trials/libretto-431/)
- people: [Lori J. Wirth](https://onco.cc/people/lori-wirth/)
- key papers: [LIBRETTO-531: selpercatinib versus cabozantinib or vandetanib in advanced RET-mutant medullary thyroid cancer](https://onco.cc/key-papers/paper-libretto-531-nejm-2023/)

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