{"entity":{"id":"paloma-2","kind":"trial","name":"PALOMA-2","aka":[],"tldr":"The trial that made palbociclib the first CDK4/6 inhibitor in routine use. It doubled progression-free time but did not extend life.","summary":"PALOMA-2, trial NCT01740427 sponsored by Pfizer and reported in 2016, is the trial that made palbociclib the first CDK4/6 inhibitor in routine use: added to letrozole as first-line treatment for postmenopausal HR-positive, HER2-negative advanced breast cancer it doubled progression-free time but did not extend life. It randomised 666 women, met its primary progression-free survival endpoint, and at the final analysis showed no significant overall survival benefit, with substantial missing survival data; with PALOMA-3 this differentiates palbociclib from ribociclib and abemaciclib on survival. OnCo links it to CDK4/6 as a target, palbociclib, aromatase inhibitors and Richard S. Finn, and the absence of a survival benefit was replicated in PALOMA-3 and the adjuvant PALLAS and PENELOPE-B trials. Whether the three drugs truly differ or the trials did is the open question.","status":"mixed","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT01740427","url":"https://clinicaltrials.gov/study/NCT01740427"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["cdk46-inhibitor"],"targets":["cdk4-6"],"drugs":["palbociclib"],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["richard-finn"],"bottlenecks":[],"keyPapers":["paper-paloma-2-n-engl-j-med-2016","paper-paloma-2-breast-cancer-res-treat-2019-update"],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT01740427","phase":"3","setting":"First-line postmenopausal HR+/HER2- advanced breast cancer: palbociclib + letrozole vs placebo + letrozole","sponsor":"Pfizer","result":"PFS HR 0.56; OS HR 0.96 (NS).","started":"2013-02-22","startedType":"actual","yearReported":2016,"enrolled":666,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Palbociclib + letrozole","n":444,"value":27.6},{"name":"Placebo + letrozole","n":222,"value":14.5}],"hr":0.56,"ci":[0.46,0.69],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1607303"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Palbociclib + letrozole","value":53.9},{"name":"Placebo + letrozole","value":51.2}],"hr":0.96,"ci":[0.78,1.18],"source":"https://doi.org/10.1056/NEJMoa1607303"}],"replication":"PFS effect replicated across all CDK4/6 trials; absence of OS benefit replicated in PALOMA-3 and the adjuvant PALLAS/PENELOPE-B trials."},"route":"/trials/paloma-2/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"technology":[{"id":"cdk46-inhibitor","kind":"technology","name":"CDK4/6 inhibitors","route":"/technologies/cdk46-inhibitor/"}],"target":[{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"}],"drug":[{"id":"letrozole","kind":"drug","name":"Letrozole (and other aromatase inhibitors)","route":"/drugs/letrozole/"},{"id":"palbociclib","kind":"drug","name":"Palbociclib","route":"/drugs/palbociclib/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"person":[{"id":"richard-finn","kind":"person","name":"Richard S. Finn","route":"/people/richard-finn/"}],"paper":[{"id":"paper-paloma-2-n-engl-j-med-2016","kind":"paper","name":"Palbociclib and Letrozole in Advanced Breast Cancer","route":"/key-papers/paper-paloma-2-n-engl-j-med-2016/"},{"id":"paper-paloma-2-breast-cancer-res-treat-2019-update","kind":"paper","name":"Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up","route":"/key-papers/paper-paloma-2-breast-cancer-res-treat-2019-update/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}