{"entity":{"id":"pada-1","kind":"trial","name":"PADA-1","aka":["PADA 1","UCBG3-05"],"tldr":"A French trial that showed, for the first time in a randomised study, that changing hormone therapy when a resistance mutation appears in the blood, before scans change, keeps breast cancer controlled for longer.","summary":"PADA-1 (NCT03079011, UNICANCER) enrolled 1,017 women at 83 French hospitals receiving an aromatase inhibitor with palbociclib as first-line treatment for ER-positive, HER2-negative advanced breast cancer and monitored circulating tumour DNA for a rising ESR1 mutation. 279 (27 per cent) developed one and 172 were randomised: switching to fulvestrant plus palbociclib gave a median progression-free survival of 11.9 months against 5.7 months for continuing, stratified hazard ratio 0.61 (Bidard et al., Lancet Oncology 2022). The abstract describes the target as ESR1-mutated subclones that may be sensitive to fulvestrant.","status":"positive","asOf":"2026-11-04","links":[{"label":"ClinicalTrials.gov NCT03079011","url":"https://clinicaltrials.gov/study/NCT03079011"},{"label":"Bidard et al., Lancet Oncol 2022","url":"https://doi.org/10.1016/S1470-2045(22)00555-1"}],"tags":[],"related":["serena-6"],"cancers":["breast-hr-positive"],"sections":[],"technologies":["liquid-biopsy"],"targets":["estrogen-receptor"],"drugs":["palbociclib","fulvestrant","letrozole"],"companies":["unicancer"],"institutions":[],"pathways":[],"terms":["esr1-mutation","ctdna"],"trials":[],"people":["francois-clement-bidard"],"bottlenecks":[],"keyPapers":["paper-bidard-pada-1-lancet-oncol-2022"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03079011","phase":"3","setting":"First-line aromatase inhibitor plus palbociclib for ER-positive, HER2-negative metastatic breast cancer, monitored for a rising ESR1 mutation in blood; patients with a rising mutation and no progression randomised to switch to fulvestrant plus palbociclib or continue","sponsor":"UNICANCER","result":"Median PFS 11.9 vs 5.7 months, HR 0.61 (0.43 to 0.86), p = 0.0040.","started":"2017-03-22","startedType":"actual","yearReported":2022,"enrolled":1017,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival from randomisation","primary":true,"unit":"months","arms":[{"name":"Switch to fulvestrant + palbociclib","n":88,"value":11.9},{"name":"Continue aromatase inhibitor + palbociclib","n":84,"value":5.7}],"hr":0.61,"ci":[0.43,0.86],"p":"0.0040","source":"https://doi.org/10.1016/S1470-2045(22)00555-1"}],"replication":"SERENA-6 applied the same switch-at-ESR1-emergence strategy with camizestrant and was also positive."},"route":"/trials/pada-1/","neighbours":{"trial":[{"id":"serena-6","kind":"trial","name":"SERENA-6","route":"/trials/serena-6/"}],"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"target":[{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"drug":[{"id":"fulvestrant","kind":"drug","name":"Fulvestrant","route":"/drugs/fulvestrant/"},{"id":"letrozole","kind":"drug","name":"Letrozole (and other aromatase inhibitors)","route":"/drugs/letrozole/"},{"id":"palbociclib","kind":"drug","name":"Palbociclib","route":"/drugs/palbociclib/"}],"company":[{"id":"unicancer","kind":"company","name":"UNICANCER","route":"/companies/unicancer/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"esr1-mutation","kind":"term","name":"ESR1 mutation","route":"/terms/esr1-mutation/"}],"person":[{"id":"francois-clement-bidard","kind":"person","name":"François-Clément Bidard","route":"/people/francois-clement-bidard/"}],"paper":[{"id":"paper-bidard-pada-1-lancet-oncol-2022","kind":"paper","name":"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","route":"/key-papers/paper-bidard-pada-1-lancet-oncol-2022/"}],"bottleneck":[{"id":"b-subclone-attribution-residual-disease","kind":"bottleneck","name":"Naming which clone or phenotype is left after treatment","route":"/bottlenecks/b-subclone-attribution-residual-disease/"}],"biomarker":[{"id":"esr1-mutation-ctdna","kind":"biomarker","name":"ESR1 mutation (ligand-binding domain, usually in ctDNA)","route":"/biomarkers/esr1-mutation-ctdna/"}]}}