|| Breast Cancer
|| ER-positive HER2-negative advanced breast cancer
| Mode of Action
|| Kinase inhibitor (chemotherapy)
| Approval Status
|| EMA approved (EU); FDA approved (USA); TGA approved (AUS)
| CAS Number || 571190-30-2
| HS Code
|| 75 mg, 125 mg, 100 mg
Who is palbociclib for?
Palbociclib is indicated for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease . It is indicated in combination with an aromatase inhibitor (an hormonal therapy) as initial endocrine based therapy in postmenopausal women or fulvestrant in women with disease progression following endocrine therapy .
Complete information about palbociclib dosage and administration can be found here 
The standard dosage is:
Consult your treating doctor for personalised dosing.
- 125 mg daily for 21 consecutive days, followed by 7 days off treatment with letrozole 2.5 mg daily continuously throughout the 28-day cycle .
What is palbociclib and how does it work?
Palbociclib is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6.
Before a cell can divide, it has to go through four phases. The first phase is a growth phase (G1-phase), the second a synthesis phase (S-phase), the third another growth phase (G2-phase) and the last phase, where the cell divides (M-phase). Cancer cells divide exceedingly fast, passing through these 4 phases rapidly. Palbociclib blocks the progression from the first G1-phase, into the second S-phase. It does this by inhibiting the cyclin-dependent kinases 4 and 6 (CDK4 and CDK6)—two proteins that are involved in entering the S-phase 
What is palbociclib's approval status?
Palbociclib was approved by
- FDA (USA) on February 3, 2015,
for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease 
. On March 31, 2017, the accelerated approval was converted into a regular approval for use in combination with an aromatase inhibitor (an hormonal therapy) as initial endocrine based therapy in postmenopausal women or fulvestrant in women with disease progression following endocrine therapy 
- EMA (EU) on November 11, 2016 ,
- TGA (AUS) on May 3, 2017 ,
for use in combination with an aromatase inhibitor (e.g. letrozole) or with fulvestrant for the treatment of women with HR+/HER2- locally advanced or metastatic breast cancer who have received prior endocrine therapy.The efficacy of palbociclib on ER-positive, HER2-negative, advanced breast cancer
was investigated in three main studies named PALOMA-1, PALOMA-2, and PALOMA-3.
PALOMA-1 was a randomised, multicentre, open-label trial in postmenopausal women with ER-positive, HER2-negative, advanced (locally advanced or metastatic) breast cancer who had not received previous systemic treatment for advanced disease. The trial enrolled 165 patients randomly allocated to receive either palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg daily continuously throughout the 28-day cycle) or letrozole alone. The progression-free survival (PFS) was 20.2 months in the palbociclib plus letrozole arm and 10.2 months in the letrozole alone arm. Overall response rate in patients with measurable disease was higher in the palbociclib plus letrozole compared to the letrozole alone arm (55.4 % versus 39.4 %) 
PALOMA-2 involved 666 untreated women. They received either palbociclib and letrozole (an aromatase inhibitor) or placebo and letrozole. The median PFS in women taking palbociclib and letrozole was on average 24.8 months (95 % CI 22.1, non-estimable) 
compared with 14.5 months (95 % CI 12.9, 17.1) 
for women taking placebo and letrozole 
PALOMA-3 involved 521 women who received either palbociclib and fulvestrant or a placebo and fulvestrant. The median PFS in women taking palbociclib and fulvestrant was 9.5 months (95 % CI 9·2–11·0) compared with 4.6 months (95 % CI 3·5–5·6) for women taking placebo and fulvestrant 
Most common adverse reactions with palbociclib are neutropenia, leukopenia, fatigue, anemia, and infection, nausea 
In March 2017 the German Institute for Quality and Efficiency in Health Care raised its doubts regarding the added benefit of palbociclib 
Summary of Product Characteristics: Ibrance (palbociclib), Pfizer Inc., FDA, Mar. 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207103s004lbl.pdf
FDA Approved Drugs. Palbociclib, 03/02/2015, cited on 30/09/2015. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm432886.htm
Finn R.S., et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. The Lancet Oncology. 2015 Jan; 16(1):25-35 http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)71159-3/abstract
Pfizer Press Release: Ibrance (palbociclib) Receives Approval in European Union for the Treatment of Women with HR+/HER2- Metastatic Breast Cancer, 10/11/2016. http://www.pfizer.com/news/press-release/press-release-detail/ibrance_palbociclib_receives_approval_in_european_union_for_the_treatment_of_women_with_hr_her2_metastatic_breast_cancer
EMA. Human Medicines: Ibrance (palbociclib), 25/11/2016 , cited on 30/11/2016. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003853/human_med_002034.jsp&mid=WC0b01ac058001d124
IQWiG finds no added benefit for breast cancer drug Ibrance. The pharma letter. 04/03/2017. http://www.thepharmaletter.com/article/iqwig-finds-no-added-benefit-for-breast-cancer-drug-ibrance
Palbociclib in advanced breast cancer: Disadvantages predominate in certain patients. IQWiG. 01/03/2017. https://www.eurekalert.org/pub_releases/2017-03/ifqa-pia030217.php
Summary of Product Characteristics: Ibrance (palbociclib), Pfizer Ltd., FDA, May 2017. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003853/WC500217196.pdf
Cristofanilli M., et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. The Lancet Oncology, 2016 Apr; 17(4):425-439. http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00613-0/fulltext
Finn R.S., et.al. PALOMA-2: Primary Results From a Phase III Trial of Palbociclib Plus Letrozole Compared With Placebo Plus Letrozole in Postmenopausal Women With ER+/HER2- Advanced Breast Cancer. ASCO University: Meeting Library. 2016 Jun. http://meetinglibrary.asco.org/content/165131-176
Summary of Product Characteristics: Ibrance (palbociclib), Pfizer Australia Ltd., TGA, May 2017. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2017-PI-01659-1&d=2017051116114622483
Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Medicine information contained herein may be time sensitive. The absence of a warning for a given medicine or combination thereof in no way should be construed to indicate that the medicine or combination is safe, effective or appropriate for any given patient. Always consult your treating physician before starting a course of treatment.