spec sheet6 rows
Palbociclib is an oral CDK4 and CDK6 inhibitor given together with hormonal therapy for hormone receptor positive, HER2 negative advanced breast cancer.
- Fry's 2004 paper characterised PD 0332991 as a selective CDK4/6 inhibitor with IC50 values of 11 nM for CDK4/cyclin D1 and 16 nM for CDK6/cyclin D2 and essentially no activity against a panel of other kinases [1].
- PALOMA-2 randomised 666 postmenopausal women and doubled median progression-free survival with palbociclib plus letrozole versus letrozole alone, 24.8 versus 14.5 months (HR 0.58) [4].
- PALOMA-3 showed the same effect after progression on endocrine therapy: median progression-free survival 9.2 versus 3.8 months with palbociclib plus fulvestrant (HR 0.42) [3].
- The final PALOMA-2 analysis did NOT demonstrate a statistically significant overall survival benefit despite the large progression-free survival gain [7]; an important qualification when describing what palbociclib delivers.
- Both adjuvant trials in early breast cancer were negative: PALLAS found no improvement in invasive disease-free survival from adding two years of palbociclib to endocrine therapy [6], and PENELOPE-B also failed in patients with residual disease after neoadjuvant chemotherapy [5].
- Neutropenia is the dominant toxicity, grade 3 or 4 in about 66% of patients, but it reflects reversible cytostatic marrow arrest rather than cell killing, which is why febrile neutropenia remains rare at roughly 1.8% [4].
Mechanism
Blocking cyclin dependent kinases 4 and 6 prevents phosphorylation of the retinoblastoma protein, so the cell cannot pass the G1 checkpoint and stops dividing. The same checkpoint governs normal bone marrow, which is why neutropenia is dose limiting and is managed by counting neutrophils rather than by waiting for symptoms.
receptor fingerprint
CDK4 in complex with cyclin (cyclin-dependent kinase 4)ATP-competitive, highly selective inhibitor
CDK6 in complex with cyclin (cyclin-dependent kinase 6)ATP-competitive inhibitor
CYP3ASubstrate and time-dependent inhibitor
Retinoblastoma protein (RB1) phosphorylation at Ser780/Ser795Blocked
E2F-dependent transcription and S-phase entrySuppressed
Safetyrisks and cautions, not medical advice
an oral antineoplastic dosed against serial neutrophil counts, where neutropenia is the expected effect rather than a rare one
Subjective profileweighing the evidence above
Real and useful medicine for the specific breast cancer it was built for, given together with hormonal therapy rather than instead of it. What puts it out of reach is not toxicity in the abstract but the monitoring: neutropenia is not a rare event here, it is the expected effect, and the schedule is steered by counts drawn before each cycle. A drug governed by a laboratory value the person cannot see is not one anyone should be buying, so the site describes it and stops there.
Resources
No suppliers are provided for compounds like this. This entry is here for reference.
Research
- 2004first citedSpecific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activ…
- 2024most recentOverall Survival With Palbociclib Plus Letrozole in Advanced Breast Cancer
- 1.Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts
- 2.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.
- 3.Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer
- 4.Palbociclib and Letrozole in Advanced Breast Cancer
- 5.Palbociclib for Residual High-Risk Invasive HR-Positive and HER2-Negative Early Breast Cancer; The Penelope-B Trial
- 6.Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)
- 7.Overall Survival With Palbociclib Plus Letrozole in Advanced Breast Cancer
7 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
Notes and cautions
- Palbociclib carries no boxed warning.
- Neutropenia is the principal adverse effect and occurs at grade 3 or 4 in roughly two-thirds of patients, but because CDK4/6 inhibition causes reversible cytostatic arrest of marrow progenitors rather than cell death, febrile neutropenia is uncommon; complete blood counts are required before starting, on day 1 and day 15 of the first two cycles, and before each subsequent cycle, with dose interruption or reduction for grade 3 or 4 counts.
- Severe or fatal interstitial lung disease and pneumonitis have been reported, and treatment should be interrupted for new or worsening respiratory symptoms and permanently discontinued for severe cases.
- Palbociclib is a CYP3A substrate, so strong CYP3A inhibitors and inducers must be avoided or the dose adjusted, and grapefruit should be avoided.
- It is embryo-fetal toxic and requires effective contraception; the negative adjuvant results (PMID 34874182, PMID 33793299) and the absence of a significant survival gain in PALOMA-2 [7] should temper claims about its benefit.