爱博斯Ibrance（帕博西尼palbociclib）

1 INDICATIONS AND USAGE
Ibrance is indicated in combination with letrozole for the initial endocrine-based treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer for metastatic disease.
This indication is approved under accelerated approval based on progression-free survival (PFS) [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon demonstration and description of clinical benefit in confirmatory trials.

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Information
The recommended dose of IBRANCE is one 125 mg capsule taken orally once daily for 21 days, followed by 7 days without treatment for a complete 28-day cycle. IBRANCE should be taken with food throughout the 28-day cycle in combination with letrozole 2.5 mg once daily. Patients should be encouraged to take their doses at approximately the same time each day.
If a patient vomits or misses a dose, they should not take another dose that day. Take the next prescribed dose at the usual time. IBRANCE capsules should be swallowed whole (do not chew, crush, or open capsules before swallowing). Capsules should not be ingested if broken, crushed, or incomplete.

2.2 Dose Adjustments
IBRANCE dose adjustments are recommended based on individual safety and tolerability
Dose Adjustments for Use with Strong CYP3A Inhibitors
Avoid concomitant use of strong CYP3A inhibitors and consider alternative concomitant medications with no or little CYP3A inhibitory effect. If patients must be coadministered with a strong CYP3A inhibitor, reduce IBRANCE dose to 75 mg once daily. If the strong inhibitor is discontinued, increase IBRANCE dose (after 3–5 half-lives of the inhibitor) to the dose used prior to initiation of the strong CYP3A inhibitor [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

3 Dosage Forms and Strengths
125 mg Capsules: Opaque hard gelatin capsules, size 0, with caramel cap and body, printed in white ink on the cap and “PBC 125” on the body.
100 mg capsules: opaque hard gelatin capsules, size 1, with caramel cap and light orange body, printed in white ink on the cap, “PBC 100” on the body.

75 mg capsules: opaque hard gelatin capsules, size 2, with light orange cap and body, printed in white ink on the cap, “PBC 75” on the body.

4 Contraindications
None

5 Warnings and Precautions
5.1 Neutropenia
Decreases in neutrophil counts have been observed in clinical trials with IBRANCE. Grade 3 (57%) or 4 (5%) decreases in neutrophil counts were reported in patients receiving IBRANCE plus letrozole in the randomized clinical trial (Study 1). The median time to first onset of any grade neutropenia per laboratory data was 15 days (range, 13-117 days). The median duration of ≥Grade 3 neutropenia was 7 days [see Adverse Reactions (6.1)].

Febrile neutropenia events have been reported in the IBRANCE clinical program, although no cases of febrile neutropenia were observed in Study 1. Monitor complete blood counts prior to initiation of IBRANCE treatment and at the start of each cycle, as well as on Day 14 of the first two cycles, and as clinically indicated. Dose interruptions, dose reductions, or delayed treatment cycle initiation are recommended for patients who develop Grade 3 or 4 neutropenia.

5.2 Infections
In Study 1, infections were reported at a higher rate in patients treated with IBRANCE plus letrozole compared to patients treated with letrozole alone. Grade 3 or 4 infections occurred in 5% of patients treated with IBRANCE plus letrozole, whereas no patients treated with letrozole alone experienced Grade 3 or 4 infections. Monitor patients for signs and symptoms of infection and treat as medically appropriate.

5.3 Pulmonary Embolism
In Study 1, pulmonary embolism was reported at a higher rate in patients treated with IBRANCE plus letrozole (5%) compared to no cases in patients treated with letrozole alone. Monitor patients for signs and symptoms of pulmonary embolism and treat as medically appropriate.

5.4 Embryo-Fetal Toxicity
Based on findings in animals and its mechanism of action, IBRANCE can cause fetal harm. IBRANCE caused embryo-fetal toxicity in rats and rabbits at maternal exposures greater than or equal to 4 times the human clinical exposure based on area under the curve (AUC). Advise females of reproductive potential to use effective contraception during treatment with IBRANCE and for at least 2 weeks after the last dose.

6 ADVERSE REACTIONS
The following headings are described elsewhere in the labeling:
● Neutropenia
● Infections
● Pulmonary Embolism

6.1 Clinical Study Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of IBRANCE (125 mg/day) plus letrozole (2.5 mg/day) compared with letrozole alone was evaluated in Study 1. The data described below reflect exposure to IBRANCE in 83/160 patients with ER-positive, HER2-negative advanced breast cancer who received at least 1 dose of treatment in Study 1. The median duration of treatment was 13.8 months for palbociclib and 7.6 months for the letrozole-alone arm.

Dose reductions due to an adverse reaction of any grade occurred in 36% of patients receiving IBRANCE plus letrozole in Study 1. No dose reductions were allowed for letrozole.

Permanent discontinuation due to an adverse reaction occurred in 7/83 (8%) patients receiving IBRANCE plus letrozole and 2/77 (3%) patients receiving letrozole alone. Adverse reactions leading to discontinuation in patients receiving IBRANCE plus letrozole included neutropenia (6%), asthenia (1%), and fatigue (1%).

The most common adverse reactions of any grade (≥10%) reported in patients in the IBRANCE plus letrozole arm were neutropenia, leukopenia, fatigue, anemia, upper respiratory tract infection, nausea, stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting, asthenia, peripheral neuropathy, and epistaxis.

The most frequently reported serious adverse reactions in patients receiving IBRANCE plus letrozole were pulmonary embolism (3/83; 4%) and diarrhea (2/83; 2%).

An increased incidence of infectious events was observed in the palbociclib plus letrozole arm (55%) compared to the letrozole alone arm (34%). Febrile neutropenia events have been reported in the IBRANCE clinical program, although no cases were observed in Study 1. Grade ≥3 neutropenia was managed with dose reductions and/or dose delays or temporary discontinuation consistent with a 6% rate of permanent discontinuation due to neutropenia