# Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial

Source: https://onco.cc/key-papers/paper-bidard-pada-1-lancet-oncol-2022/  
OnCo record `paper-bidard-pada-1-lancet-oncol-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Switching hormone therapy when a resistance mutation rose in the blood, before scans showed progression, roughly doubled the time cancer stayed controlled in PADA-1.

## Summary

PADA-1 monitored 1,017 women on first-line aromatase inhibitor plus palbociclib for ER-positive, HER2-negative advanced breast cancer at 83 French hospitals for a rising ESR1 mutation in blood. 279 (27 per cent) developed one and 172 (17 per cent) were randomised, without synchronous progression, to switch to fulvestrant plus palbociclib (88) or continue (84). Median progression-free survival from randomisation was 11.9 months (95% CI 9.1 to 13.6) against 5.7 months (3.9 to 7.5), stratified hazard ratio 0.61 (0.43 to 0.86), p = 0.0040. Neutropenia was the commonest grade 3 or worse haematological event.

## Fields

- Kind: Key paper
- Last checked: 2026-11-04
- Journal: The Lancet Oncology
- Year: 2022
- DOI: 10.1016/S1470-2045(22)00555-1
- Authors: Bidard FC, Hardy-Bessard AC, Dalenc F, et al.
- Findings: 279 of 1,017 (27%) developed a rising blood ESR1 mutation; 172 randomised.; Median PFS 11.9 vs 5.7 months; HR 0.61 (0.43 to 0.86), p = 0.0040.
- What it means: The first randomised proof that acting on a resistant subclone seen in blood, before scans change, can help. It works because ESR1-mutant subclones are common and the mutation can be read directly.
- Caveats: Open label.; Advanced disease, at tumour fractions far above residual-disease levels.

## Sources

- Bidard et al., Lancet Oncol 2022 (PADA-1): https://doi.org/10.1016/S1470-2045(22)00555-1
- PubMed: https://pubmed.ncbi.nlm.nih.gov/36183733/

## Connected records

- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [Estrogen receptor (ERα)](https://onco.cc/targets/estrogen-receptor/)
- drugs: [Fulvestrant](https://onco.cc/drugs/fulvestrant/), [Letrozole (and other aromatase inhibitors)](https://onco.cc/drugs/letrozole/), [Palbociclib](https://onco.cc/drugs/palbociclib/)
- companies: [UNICANCER](https://onco.cc/companies/unicancer/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [ESR1 mutation](https://onco.cc/terms/esr1-mutation/)
- trials: [PADA-1](https://onco.cc/trials/pada-1/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)
- biomarkers: [ESR1 mutation (ligand-binding domain, usually in ctDNA)](https://onco.cc/biomarkers/esr1-mutation-ctdna/)

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