Palbociclib

Overview

Palbociclib, sold under the brand name Ibrance among others, is an anti-cancer medication used for the treatment of HR-positive and HER2-negative breast cancer. It was developed by Pfizer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Palbociclib was the first CDK4/6 inhibitor to be approved as a cancer therapy.[1–4] WP

The most common side effects include neutropenia (low blood levels of neutrophils, a type of white blood cell that fights infection), infections, leucopenia (low white blood cell counts), tiredness, nausea (feeling sick), stomatitis (inflammation of the lining of the mouth), anemia (low red blood cell counts), diarrhea, alopecia (hair loss), and thrombocytopenia (low blood platelet counts). The most common severe side effects include neutropenia, leucopenia, infections, anemia, tiredness, and increased blood levels of liver enzymes (aspartate and alanine transaminases).[5] WP

Uses, dosage and effects

Medical uses

Palbociclib is indicated for the treatment of adults with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy; or fulvestrant in people with disease progression following endocrine therapy.[1][5] WP

Palbociclib is indicated in combination with inavolisib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer, as detected by an FDA‑authorized test, following recurrence on or after completing adjuvant endocrine therapy.[1][6] WP

Palbociclib is indicated in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of adults with hormone receptor-positive, human epidermal growth factor receptor 2‑positive locally advanced or metastatic breast cancer following induction treatment.[1][7] WP

Risks and side effects

Adverse effects

The most common side effects include neutropenia (low blood levels of neutrophils, a type of white blood cell that fights infection), infections, leucopenia (low white blood cell counts), tiredness, nausea (feeling sick), stomatitis (inflammation of the lining of the mouth), anemia (low red blood cell counts), diarrhea, alopecia (hair loss), and thrombocytopenia (low blood platelet counts). The most common severe side effects include neutropenia, leucopenia, infections, anemia, tiredness, and increased blood levels of liver enzymes (aspartate and alanine transaminases). Leukopenia and anemia are also frequent among patients taking palbociclib. More than 10% of patients also experience side effects such as fatigue, nausea, diarrhea, respiratory infection, headache, thrombocytopenia, vomiting, and decreased appetite.[5][8][9] WP

Pharmacology

Mechanism of action

It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6.[2][3] WP

In the G1 phase of the cell cycle, mammalian cells must pass a checkpoint, known as the restriction point "R", in order to complete the cell cycle and divide. CDK4 and CDK6 complex with Cyclin D drive the phosphorylation of the retinoblastoma protein, Rb, which allows the cell to pass R and commit to division. Regulation of one or more proteins involved in this checkpoint is lost in many cancers. However, by inhibiting CDK4/6, palbociclib ensures that the cyclin D-CDK4/6 complex cannot aid in phosphorylating Rb. This prevents the cell from passing R and exiting G1, and in turn from proceeding through the cell cycle.[10] WP

Legal status

Legal status

The drug was reviewed and approved under the US Food and Drug Administration's (FDA) accelerated Priority Review and Breakthrough Therapy designation programs on February 3, 2015, as a treatment (in combination with letrozole) for people with estrogen receptor positive (ER+) advanced breast cancer. This was an accelerated approval.[11][12] WP

In March 2017, the FDA granted regular approval to palbociclib for hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor.[8] WP

A phase III trial, PALOMA-2, was fully enrolled by February 2015 and reported positive results in April 2016. The results of PALOMA-2 trial, published in November 2016, showed significantly longer progression-free survival in patients on palbociclib in combination with letrozole, compared to patients on letrozole and placebo. Progression-free survival was assessed by radiologically-confirmed disease progression by RECIST criteria or death during the study. At the time of publication, there was insufficient data on overall survival, and a final analysis is planned after a total of 390 deaths occur per protocol and in agreement with regulatory agencies. Of note, it was noted that the addition of palbociclib caused higher rates of myelotoxic events in the study.[13][14] WP

The drug was approved for use in the European Union in November 2016, as a treatment for hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or, for women who have received prior endocrine therapy, in combination with fulvestrant. In pre- or perimenopausal women, a luteinizing hormone releasing hormone agonist should also be given.[15] WP

In December 2017, palbociclib, was accepted for use by the NHS after going through the Scottish Medicines Consortium's process for medicines used to treat very rare and end-of-life breast cancer.[16] WP

Economics

Palbociclib "can be ordered through select" specialty pharmacies and "sells for $9,850 for 30 days or $118,200 for a year's supply before discounts." According to a statement by the New York–based Pfizer the price "is not the cost that most patients or payors pay" since most prescriptions are dispensed through health plans, which negotiate discounts for medicines or get government-mandated price concessions. In the United States specialty pharmacies fill prescriptions for drugs that are usually high cost.[17][18][19] WP

Pfizer reported revenue of US$4.753 billion for Ibrance in 2023.[20] WP

Resistance to cost

In February 2017, the National Institute for Health and Care Excellence (NICE) in the United Kingdom published a statement stating that the cost of Ibrance (approximately US$3700/28 days) did not make the added health benefits worth the cost. It was stated that with the side effects caused by Ibrance, it was not a cost-effective medication for NICE to endorse. At the time, a year's treatment with palbociclib and a drug such as fulvestrant was priced at US$106,105 (£79,650). In November 2017 NICE announced that, after negotiation with Pfizer, the price would be discounted, and the drug would be recommended for use.[21][22][23] WP

Chemistry

Formula

C24H29N7O2 PC

CAS number

571190-30-2 PC

Molar mass (g/mol)

447.5 PC

IUPAC name (computed by PubChem)

6-acetyl-8-cyclopentyl-5-methyl-2-[(5-piperazin-1-yl-2-pyridinyl)amino]pyrido[2,3-d]pyrimidin-7-one PC

SMILES

CC1=C(C(=O)N(C2=NC(=NC=C12)NC3=NC=C(C=C3)N4CCNCC4)C5CCCC5)C(=O)C PC

InChIKey

AHJRHEGDXFFMBM-UHFFFAOYSA-N PC

PubChem CID

5330286

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Ibrance- palbociclib capsule. 25 February 2026
2. Journal / agency Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, Ginther C, Atefi M, Chen I, Fowst C, Los G, Slamon DJ. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Research. 2009. doi:10.1186/bcr2419 · PMID 19874578 · PMC2790859
3. Journal / agency Rocca A, Farolfi A, Bravaccini S, Schirone A, Amadori D. Palbociclib (PD 0332991): targeting the cell cycle machinery in breast cancer. Expert Opinion on Pharmacotherapy. February 2014. doi:10.1517/14656566.2014.870555 · PMID 24369047
4. Other Updated Data from Phase 3 Trial of Ibrance (palbociclib) Plus Letrozole in HR+, HER2- Metastatic Breast Cancer Confirm Improvement in Progression-Free Survival
5. Journal / agency Ibrance EPAR. 9 November 2016
6. Journal / agency FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer. 10 October 2024
7. Journal / agency FDA approves palbociclib with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of HR-positive, HER2-positive metastatic breast cancer. 24 June 2026
8. Journal / agency Approved Drugs - Palbociclib (Ibrance)
9. Journal / agency Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. The New England Journal of Medicine. July 2015. doi:10.1056/NEJMoa1505270 · PMID 26030518
10. Journal / agency Xu H, Yu S, Liu Q, Yuan X, Mani S, Pestell RG, Wu K. Recent advances of highly selective CDK4/6 inhibitors in breast cancer. Journal of Hematology & Oncology. April 2017. doi:10.1186/s13045-017-0467-2 · PMID 28438180 · PMC5404666
11. Other FDA Approves Palbociclib for Metastatic Breast Cancer. 3 Feb 2015
12. Other Pfizer Receives U.S. FDA Accelerated Approval of Ibrance (palbociclib). 3 Feb 2015
13. Other Late-stage study of expanded use of Pfizer's Ibrance successful; global regulatory applications to follow. April 2016. 19 April 2016
14. Journal / agency Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and Letrozole in Advanced Breast Cancer. The New England Journal of Medicine. November 2016. doi:10.1056/NEJMoa1607303 · PMID 27959613
15. Journal / agency Ibrance (palbociclib) European public assessment report
16. Other Breast cancer drug approved for NHS use. 2017-12-11
17. Other Pfizer breast cancer drug gets early FDA approval. 3 February 2015
18. Other Herper M. The World's Most Expensive Drugs. 19 February 2010
19. Other Thomas K, Pollack A. Specialty Pharmacies Proliferate, Along With Questions. 15 July 2015
20. Other Pfizer's year in review. 31 December 2023
21. Other UK agency says Pfizer breast cancer drug too expensive. 3 February 2017
22. Other Breast cancer drug costs too high in relation to benefits for routine NHS funding
23. Other Breast cancer patients to have routine access to two life extending drugs after new deal, say NICE in draft guidance

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.