1. Ibrance® - Palbociclib
Manufacturer: Pfizer
FDA Approval Date: February 3, 2015

2. 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

3. Ibrance® - Palbociclib Clinical Application
Contraindications:
none
Warnings and Precautions:
Neutropenia
Infections
Pulmonary embolism
Embryo-Fetal toxicity

4. 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

5. 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

6. 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 E
Feces (74% as metabolites); Urine (17.5% as metabolites); mean plasma half-life of 29 +/- 5 hrs.

7. 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

8. Ibrance® - Palbociclib Drug Interactions
Drug Interactions – Precipitant Drugs:
Strong CYP3A4 inhibitors  concentration of Ibrance (palbociclib)
Strong CYP3A4 inducers: ↓ concentration of Ibrance (palbociclib)

9. 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

10. 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.

11. Ibrance® - Palbociclib Prescription Information
Cost:
125 mg, 100 mg and 75 mg $11, for one month supply (21 capsules)
Lexi-Comp via UpToDate; Accessed 3/6/2015

12. 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:

13. 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:

14. 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:

15. 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
Nausea 13
Diarrhea 21 10
Alopecia 22
Fatigue 41 23
Finn, RS, et al., Lancet Oncol 2015;16:

16. 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)
0.488 (0.319, 0.748)
Median PFS [months] (95%CI)
20.2 (13.8, 27.5)
10.2 (5.7, 12.6)
Finn, RS, et al., Lancet Oncol 2015;16:

17. 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:

18. 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

19. Ibrance® - Palbociclib References
Ibrance full prescribing infromation. Pfizer. Feb. 2015
Palbociclib. Drug information. Lexicomp Drug Information. Accessed through UpToDate. Accessed on February 15, 2015.
Finn et al., The cyclin dependent kinase 4/6 inhibitor palbociclib in combination with letrozole vs letrozole alone as first linetreatment of estrogen receptor- positive HER2 negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomized phase 2 study. Lancet Oncol. 2015;16: 25-35