# LIBRETTO-001: selpercatinib in RET fusion-positive non-small-cell lung cancer

Source: https://onco.cc/key-papers/paper-libretto-001-selpercatinib-nsclc-nejm-2020/  
OnCo record `paper-libretto-001-selpercatinib-nsclc-nejm-2020` (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 shrank tumours in 64 percent of previously treated and 85 percent of untreated patients with RET fusion-positive lung cancer, including brain metastases, and led to the first approval for this driver.

## Summary

Phase 1/2 study of 105 previously treated and 39 treatment-naive patients with RET fusion-positive non-small-cell lung cancer treated with selpercatinib.

Objective response was 64 percent in previously treated patients with median duration of response 17.5 months and median progression-free survival 16.5 months; 85 percent in treatment-naive patients; intracranial response 91 percent among evaluable patients. Hypertension, liver enzyme rise and QT prolongation were the main toxicities.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2020
- DOI: 10.1056/NEJMoa2005653
- Authors: Drilon A, Oxnard GR, Tan DSW, et al.
- Findings: Objective response 64 percent (previously treated) and 85 percent (treatment-naive).; Median progression-free survival 16.5 months in previously treated patients.
- What it means: RET fusion testing is standard in lung adenocarcinoma and selpercatinib the preferred first-line RET inhibitor, confirmed against chemo-immunotherapy in LIBRETTO-431.
- Caveats: Single-arm study.; Hypersensitivity reactions in patients recently treated with immunotherapy.

## Sources

- N Engl J Med 2020: https://doi.org/10.1056/NEJMoa2005653
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32846060/

## Connected records

- cancers: [RET fusion-positive non-small-cell lung cancer](https://onco.cc/cancers/ret-fusion-nsclc/)
- drugs: [Selpercatinib](https://onco.cc/drugs/selpercatinib/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- roadmaps: [Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/)
- trials: [A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRET](https://onco.cc/trials/nct03157128/)

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