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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.
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.
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.
Shares ESR1 mutation (ligand-binding domain, usually in ctDNA), ESR1 mutation, Estrogen receptor (ERα), The Lancet Oncology.
Shares PADA-1, Fulvestrant, Estrogen receptor (ERα), Liquid biopsy (ctDNA).
Shares Letrozole (and other aromatase inhibitors), Palbociclib, Fulvestrant.
Shares ESR1 mutation (ligand-binding domain, usually in ctDNA), Letrozole (and other aromatase inhibitors), Palbociclib, Fulvestrant.
Shares Palbociclib, Estrogen receptor (ERα), Liquid biopsy (ctDNA), HR-positive / HER2-negative breast cancer.
Shares Palbociclib, Fulvestrant, HR-positive / HER2-negative breast cancer.
Shares Letrozole (and other aromatase inhibitors), Palbociclib, Fulvestrant, Estrogen receptor (ERα).
Shares Letrozole (and other aromatase inhibitors), Palbociclib, Fulvestrant, HR-positive / HER2-negative breast cancer.
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