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Ibrance® - Palbociclib
Manufacturer: Pfizer
FDA Approval Date: February 3, 2015
Ibrance® - Palbociclib
Clinical Application
• Indications:
• Treatment of post-menopausal women
with estrogen positive, human epidermal
growth factor negative advanced breast
cancer
• Place in therapy:
• Only non hormonal therapy for advanced
ER+ breast cancer
Ibrance® - Palbociclib
Clinical Application
• Contraindications:
• none
• Warnings and Precautions:
• Neutropenia
• Infections
• Pulmonary embolism
• Embryo-Fetal toxicity
Ibrance® - Palbociclib
Clinical Application
• Pregnancy:
• Category not currently assigned (likely X)
• Adverse events observed in animal
reproduction studies
• Lactation:
• Excretion in breast milk not known
• Not recommended
Ibrance® - Palbociclib
Drug Facts
• Pharmacology:
• Inhibitor of cyclin-dependent kinase
(CDK) 4 and 6
• Reduces cellular proliferation by
blocking progression of the cell from
G1 into S phase of cell cycle
Brand®or™ - Generic
Drug Facts
• Pharmacokinetics:
A
Bioavialibility: 46%. Cmax: 6-12 hours
D
85% protein bound with mean Vd of 2583 L
M
Extensive hepatic metabolism
predominately via CYP3A4 and SULT2A1
Feces (74% as metabolites); Urine (17.5%
as metabolites); mean plasma half-life of 29
+/- 5 hrs.
E
Ibrance® - Palbociclib
Drug Interactions
• Drug Interactions – Object Drugs:
• Weak CYP3A4 inhibitor
•  levels of CYP3A4 substrates
• Dose adjustment may be required for
agents with narrow therapeutic indices
Ibrance® - Palbociclib
Drug Interactions
• Drug Interactions – Precipitant Drugs:
• Strong CYP3A4 inhibitors  concentration
of Ibrance (palbociclib)
• Strong CYP3A4 inducers: ↓ concentration
of Ibrance (palbociclib)
Ibrance® - Palbociclib
Monitoring Parameters
• Efficacy Monitoring:
• Signs of clinical improvement
• Absence of disease progression
• Toxicity Monitoring:
• CBC with differential prior to treatment,
every 2 weeks for first 2 cycles, then
prior to each cycle
• Monitor for s/sx of infection and
pulmonary embolism
Ibrance® - Palbociclib
Prescription Information
• Dosing:
• 125 mg taken orally once daily for 21
days followed by 7 days off treatment in
28-day cycles
• Should be taken with food and in
combination with letrozole 2.5 mg once
daily continuously.
Ibrance® - Palbociclib
Prescription Information
• Cost:
• 125 mg, 100 mg and 75 mg $11,820.00
for one month supply (21 capsules)
Lexi-Comp via UpToDate; Accessed 3/6/2015
Ibrance® - Palbociclib
Literature Review
• Study Design (PALOMA-1/TRIO-18)
• Phase 2, randomized, open label trial
• 50 sites in 12 countries (North America, Latin
American and Europe)
• Interventions
• Palbociclib 125 mg daily (3 wks on/1 wk off)
+ Letrozole 2.5 mg daily
• Letrozole 2.5 mg daily
Finn, RS, et al., Lancet Oncol 2015;16: 25-35.
Ibrance® - Palbociclib
Literature Review
• Primary Endpoint:
• Progression free survival
• Secondary Endpoints:
• Objective response, clinical benefit,
duration of response, overall survival
Finn, RS, et al., Lancet Oncol 2015;16: 25-35.
Ibrance® - Palbociclib
Literature Review
Inclusion criteria
Exclusion criteria
Post-menopausal
Received treatment with
Letrozole within past 12 months
Locally recurrent disease not
amenable to surgery or
metastatic disease
Any previous treatment for
advanced breast cancer
No previous treatment for
advanced disease
Brain metastasis
ER+/Her2-
Any previous treatment with CDK
inhibitor
ECOG performance status of
0 or 1
Finn, RS, et al., Lancet Oncol 2015;16: 25-35.
Ibrance® - Palbociclib
Literature Review
• Significant Adverse Events: (>20%)
Event
Palbociclib+Letrozole
(n=83)
Letrozole
(n=77)
URI
31
18
Neutropenia
75
5
Leukopenia
43
3
Anemia
35
7
Stomatitis
25
7
Nausea
25
13
Diarrhea
21
10
Alopecia
22
3
Fatigue
41
23
Finn, RS, et al., Lancet Oncol 2015;16: 25-35.
Ibrance® - Palbociclib
Literature Review
• Efficacy Results: Investigator assessment
PFS Intent to Treat Population
Progression Free
Survival
Palbociclib +
Letrozole
(n=84)
Letrozole
(n=81)
Number of PFS Events (%)
41 (48.8%)
59 (72.8%)
Hazard Ratio (95% CI)
Median PFS [months]
(95%CI)
0.488 (0.319, 0.748)
20.2 (13.8, 27.5)
10.2 (5.7, 12.6)
Finn, RS, et al., Lancet Oncol 2015;16: 25-35.
Ibrance® - Palbociclib
Literature Review
• PALOMA-1/TRIO-18
• Conclusions
• Addition of palbociclib to letrozole
significantly improved progression free
survival in women with advanced ER+ and
HER2- breast cancer
• Phase 3 trial currently underway
Finn, RS, et al., Lancet Oncol 2015;16: 25-35.
Ibrance® - Palbociclib
Summary
• Only non-hormonal targeted therapy
approved for use in ER-positive, HER-2
negative advanced breast cancer
• First CDK inhibitor approved for use in
oncology
• Used in combination with letrozole
• Side effects: neutropenia / leukopenia
• Dose reduction is suggested as 1st step in tx
Ibrance® - Palbociclib
References
1.
http://www.Ibrance.com
2.
Ibrance full prescribing infromation. Pfizer. Feb. 2015
3.
Palbociclib. Drug information. Lexicomp Drug
Information. Accessed through UpToDate. Accessed
on February 15, 2015.
4.
Finn et al., The cyclin dependent kinase 4/6 inhibitor
palbociclib in combination with letrozole vs letrozole
alone as first linetreatment of estrogen receptorpositive HER2 negative, advanced breast cancer
(PALOMA-1/TRIO-18): a randomized phase 2 study.
Lancet Oncol. 2015;16: 25-35