IBRANCE PI Update 2016

Question 1

Indications and usage

Answer 1

IBRANCE is a kinase inhibitor indicated for the treatment of hormone receptor positive, HER2 negative advanced or metastatic breast cancer in combination with:

• letrozole in initial endocrine based therapy in postmenopausal women or -
• Fulvestrant in women with disease progression following endocrine therapy

Question 2

Contraindications

Answer 2

none

Question 3

Warnings and precautions (3)

Answer 3

1. Neutropenia
2. PE
3. Embryo-Fetal Toxicity

Question 4

CYP3A Inhibitors

Answer 4

Avoid use with IBRANCE and strong CYP3A inhibitors. If can’t be avoided lower the IBRANCE dose

Question 5

CYP3A Inducers

Answer 5

Avoid concurrent use with strong CYP3A inducers

Question 6

CYP3A Substrates

Answer 6

The dose of sensitive CYP3A substrates with narrow therapeutic indices may need to be reduced when used with IBRANCE

Question 7

Use in special populations (lactation)

Answer 7

Advise not to breastfeed

Question 8

Grade 1 or 2 dose reduction hematologic toxicities

Answer 8

No dose adjustment required

Question 9

Grade 3 Day 1 of Cycle

Answer 9

Withhold IBRANCE, repeat blood count monitoring within 1 week. When recovered to grade 2 or less start the next cycle at the SAME dose

Question 10

Grade 3 Day 14 of first 2 cycles

Answer 10

Continue IBRANCE at current dose to complete the cycle. Repeat the blood count on day 21.
Consider dose reduction in cases of prolonged - more than 1 week recovery from Grade 3 neutropenia or recurrent Grade 3 neutropenia in subsequent cycles

Question 11

Grade 3 neutropenia with fever and/or infection

Answer 11

Withhold IBRANCE until recovery to Grade 2 or less and resume at the next lower dose.

Question 12

Grade 4

Answer 12

Withhold IBRANCE until recovery to Grade 2 or less. Resume at the next lower dose.

Question 13

If patients must be coadministered a strong CYP3A inhibitor

Answer 13

Reduce IBRANCE to 75mg. If inhibitor is discontinued increase IBRANCE after 3-5 half lives of the inhibitor to the dose used prior.

Question 14

Febrile neutropenia %

Answer 14

1%

Question 15

Study 1 neutropenia %

Answer 15

75%

Question 16

Study 2 neutropenia %

Answer 16

83%

Question 17

Study 1 grade 3 or more neutropenia %

Answer 17

62%

Question 18

Study 2 grade 3 or more neutropenia %

Answer 18

66%

Question 19

Median time to first episode of any grade neutropenia

Answer 19

15 days

Question 20

Median duration of grade 3 or more neutropenia

Answer 20

7 days

Question 21

How many deaths due to sepsis in study 2

Answer 21

1

Question 22

Study 1 PE %

Answer 22

5%

Question 23

Study 2 PE %

Answer 23

1%

Question 24

Guidance on PE

Answer 24

Monitor for signs and symptoms of PE and treat as appropriate

Question 25

Guidance on Embryo-Fetal Toxicity

Answer 25

Advise on potential risk to fetus. Advise to use contraception including 3 weeks after last dose