{"entity":{"id":"palbociclib","kind":"drug","name":"Palbociclib","aka":[],"tldr":"Palbociclib was the first CDK4/6 inhibitor (2015), and in 2026 became the first approved as maintenance in HER2-positive, hormone-positive breast cancer.","summary":"Palbociclib is a reversible CDK4/6 inhibitor that halts the cell cycle at G1, given as 125 mg daily for 21 days of a 28-day cycle with an aromatase inhibitor or fulvestrant. It was the first CDK4/6 inhibitor, approved in 2015 for HR-positive, HER2-negative advanced breast cancer on PALOMA-2 and PALOMA-3, which improved progression-free but not overall survival; the adjuvant trials PALLAS and PENELOPE-B were negative. In PATINA (SABCS 2024; approved Q2 2026) adding palbociclib to anti-HER2 plus endocrine maintenance in HR-positive, HER2-positive metastatic disease extended progression-free survival by about 15 months. Pfizer markets it; neutropenia (80%) is frequent but rarely febrile. Why it lacks the survival benefit seen with ribociclib and abemaciclib is debated. For a newcomer: the drug that opened the CDK4/6 class, now finding a new home in HER2-positive disease.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Palbociclib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Palbociclib"}],"tags":[],"related":["pr-status"],"cancers":["breast-hr-positive","breast-her2-positive"],"sections":[],"technologies":["cdk46-inhibitor"],"targets":["cdk4-6"],"drugs":[],"companies":["pfizer"],"institutions":[],"pathways":[],"terms":[],"trials":["nct03709680","nct05468697","nct04553133","nct04606446","nct05867251","nct04567420","nct05501886","nct05768139","nct06065748","nct06736704","nct07002177","nct05563220","nct04711252","nct06757634","nct04862663","nct05909397","nct06380751","nct06760637","nct05226871"],"people":["massimo-cristofanilli"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"brand":"Ibrance","modality":"Small-molecule CDK4/6 inhibitor","mechanism":"Reversible CDK4/6 inhibitor.","approvals":[{"region":"US","year":2015,"indication":"HR+/HER2- advanced breast cancer with endocrine therapy"},{"region":"US","year":2026,"indication":"HR+/HER2+ advanced breast cancer maintenance with anti-HER2 and endocrine therapy"}],"mechanismSteps":["Oral drug is absorbed and reaches the tumour","Binds the ATP pocket (or allosteric site) of CDK4 and CDK6","Phosphorylation of downstream substrates stops","RB stays unphosphorylated and holds E2F; cells arrest in G1","Oncogene-addicted cells arrest and undergo apoptosis"],"dosing":{"route":"Oral","schedule":"125 mg once daily for 21 days, then 7 days off (28-day cycle), with aromatase inhibitor or fulvestrant","modifications":"Reduce to 100 then 75 mg for grade 3 neutropenia with fever or grade 4","monitoring":"Complete blood count before each cycle and on day 15 of the first two cycles; ILD symptoms","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fecbdd7d-b729-41b5-9872-231b8fe104ce"},"toxicity":[{"event":"Neutropenia","anyGradePct":80,"grade3PlusPct":66,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fecbdd7d-b729-41b5-9872-231b8fe104ce","note":"PALOMA-2 with letrozole"},{"event":"Infections","anyGradePct":60,"grade3PlusPct":7,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fecbdd7d-b729-41b5-9872-231b8fe104ce","note":"PALOMA-2 with letrozole"},{"event":"Leukopenia","anyGradePct":39,"grade3PlusPct":25,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fecbdd7d-b729-41b5-9872-231b8fe104ce","note":"PALOMA-2 with letrozole"},{"event":"Fatigue","anyGradePct":37,"grade3PlusPct":2,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fecbdd7d-b729-41b5-9872-231b8fe104ce","note":"PALOMA-2 with letrozole"},{"event":"Nausea","anyGradePct":35,"grade3PlusPct":1,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fecbdd7d-b729-41b5-9872-231b8fe104ce","note":"PALOMA-2 with letrozole"},{"event":"Alopecia","anyGradePct":33,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fecbdd7d-b729-41b5-9872-231b8fe104ce","note":"PALOMA-2 with letrozole"},{"event":"Stomatitis","anyGradePct":30,"grade3PlusPct":1,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fecbdd7d-b729-41b5-9872-231b8fe104ce","note":"PALOMA-2 with letrozole"},{"event":"Diarrhoea","anyGradePct":26,"grade3PlusPct":1,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fecbdd7d-b729-41b5-9872-231b8fe104ce","note":"PALOMA-2 with letrozole"},{"event":"Anaemia","anyGradePct":24,"grade3PlusPct":6,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fecbdd7d-b729-41b5-9872-231b8fe104ce","note":"PALOMA-2 with letrozole"},{"event":"Rash","anyGradePct":18,"grade3PlusPct":1,"source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fecbdd7d-b729-41b5-9872-231b8fe104ce","note":"PALOMA-2 with letrozole"}],"access":[{"country":"US","reimbursement":"Medicare Part D; generic entry expected 2027 in the US","assistance":"https://www.pfizeroncologytogether.com","generic":false,"source":"https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files","asOf":"2026-09-06"},{"country":"UK","reimbursement":"NICE: recommended with aromatase inhibitor (TA495) and fulvestrant (TA619)","source":"https://www.nice.org.uk/guidance/published?ngt=Technology%20appraisal%20guidance","asOf":"2026-09-06"}],"regulatoryEvents":[{"date":"2015-02-03","type":"accelerated-approval","region":"US","note":"Accelerated approval with letrozole: first CDK4/6 inhibitor (PALOMA-1)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"In combination with letrozole for postmenopausal women with ER-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for metastatic disease"},{"date":"2016-02-19","type":"approval","region":"US","note":"With fulvestrant after endocrine therapy (PALOMA-3)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2017-03-31","type":"conversion","region":"US","note":"Full approval (PALOMA-2)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications","indication":"In combination with letrozole for postmenopausal women with ER-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for metastatic disease"},{"date":"2019-04-04","type":"approval","region":"US","note":"Men with HR+/HER2- breast cancer","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications"},{"date":"2026-06-24","type":"approval","region":"US","note":"Maintenance in HR+/HER2+ advanced breast cancer with anti-HER2 and endocrine therapy (PATINA)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-palbociclib-trastuzumab-or-without-pertuzumab-and-endocrine-therapy-maintenance"},{"date":"2026-07-14","type":"approval","region":"US","note":"Gedatolisib with fulvestrant, with or without palbociclib, HR+/HER2- advanced breast cancer (VIKTORIA-1)","source":"https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-gedatolisib-fulvestrant-or-without-palbociclib-hr-positive-her2-negative-locally"}]},"route":"/drugs/palbociclib/","neighbours":{"biomarker":[{"id":"er-status","kind":"biomarker","name":"ER status (oestrogen receptor by IHC)","route":"/biomarkers/er-status/"},{"id":"pr-status","kind":"biomarker","name":"PR status (progesterone receptor by IHC)","route":"/biomarkers/pr-status/"}],"cancer":[{"id":"acral-melanoma","kind":"cancer","name":"Acral melanoma","route":"/cancers/acral-melanoma/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"invasive-lobular-carcinoma","kind":"cancer","name":"Invasive lobular carcinoma of the breast","route":"/cancers/invasive-lobular-carcinoma/"},{"id":"male-breast-cancer","kind":"cancer","name":"Male breast cancer","route":"/cancers/male-breast-cancer/"}],"technology":[{"id":"cdk46-inhibitor","kind":"technology","name":"CDK4/6 inhibitors","route":"/technologies/cdk46-inhibitor/"},{"id":"st-johns-wort-interaction","kind":"technology","name":"St John's wort: an interaction to avoid","route":"/technologies/st-johns-wort-interaction/"}],"target":[{"id":"cdk4-6","kind":"target","name":"CDK4/6","route":"/targets/cdk4-6/"}],"company":[{"id":"abcsg","kind":"company","name":"Austrian Breast & Colorectal Cancer Study Group","route":"/companies/abcsg/"},{"id":"geicam","kind":"company","name":"GEICAM Spanish Breast Cancer Group","route":"/companies/geicam/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. 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