# LIBRETTO-431: first-line selpercatinib versus chemotherapy with or without pembrolizumab in RET fusion-positive lung cancer

Source: https://onco.cc/key-papers/paper-libretto-431-nejm-2023/  
OnCo record `paper-libretto-431-nejm-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Given as first treatment, selpercatinib more than doubled the time to progression compared with platinum-pemetrexed chemotherapy plus pembrolizumab in RET fusion-positive lung cancer, and protected against brain metastases.

## Summary

Phase 3 trial of 261 patients with untreated advanced RET fusion-positive non-squamous non-small-cell lung cancer randomised to selpercatinib or platinum-pemetrexed with or without pembrolizumab.

Median progression-free survival was 24.8 versus 11.2 months (hazard ratio 0.46) in the intention-to-exclude-pembrolizumab population, response 84 versus 65 percent, and the cumulative incidence of central nervous system progression was lower with selpercatinib.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2023
- DOI: 10.1056/NEJMoa2309457
- Authors: Zhou C, Solomon B, Loong HH, et al.
- Findings: Median progression-free survival 24.8 vs 11.2 months; hazard ratio 0.46.; Objective response 84 percent vs 65 percent.
- What it means: Selpercatinib is the established first-line treatment for RET fusion-positive lung cancer, and the trial adds to evidence that targeted therapy should precede chemo-immunotherapy in driver-positive disease.
- Caveats: Open-label; overall survival immature.; Crossover to selpercatinib at progression was permitted.

## Sources

- N Engl J Med 2023: https://doi.org/10.1056/NEJMoa2309457
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37870973/

## Connected records

- cancers: [RET fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ret-fusion-nsclc/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Selpercatinib](https://onco.cc/drugs/selpercatinib/)
- trials: [LIBRETTO-431](https://onco.cc/trials/libretto-431/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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