This is an application to register a new chemical entity.
Drug class and therapeutic indication
This medicine is a first in class and stated to be a reversible, small molecule inhibitor of cyclin-dependent kinases (CDK) CDK4/ (cyclin D1) and CDK6/cyclin D2. CDK4/6 are downstream of multiple signalling pathways which lead to cellular proliferation, and palbociclib is postulated to prevent cellular proliferation by preventing G1 to S phase progression of the cell cycle.
The proposed indications taken from the Draft PI and Letter of Application dated 25 April 2016 are:
Ibrance in combination with endocrine therapy is indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer:
with letrozole as initial endocrine-based therapy in postmenopausal women
with fulvestrant in women who have received prior therapy
Dosage forms and strengths
The following is taken from the Product Information:
Ibrance is supplied as hard gelatin capsules containing 75 mg, 100 mg or 125 mg of palbociclib as the freebase and the following excipients: microcrystalline cellulose, lactose monohydrate, sodium starch glycolate, silicon dioxide and magnesium stearate.
Dosage and administration
The recommended dose of Ibrance is a 125 mg capsule taken orally once daily for 21 consecutive days followed by 7 days off treatment (Schedule 3/1) to comprise a complete cycle of 28 days.
When coadministered with palbociclib, the recommended dose of letrozole is 2.5 mg taken orally once daily continuously throughout the 28-day cycle. Please refer to the full prescribing information of letrozole.
When coadministered with palbociclib, the recommended dose of fulvestrant is 500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter. Please refer to the full prescribing information of fulvestrant.
Ibrance should be taken with food.
Patients should be encouraged to take their dose at approximately the same time each day. Continue the treatment as long as the patient is deriving clinical benefit from therapy.
If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time. Ibrance capsules should be swallowed whole (do not chew, crush or open them prior to swallowing). No capsule should be ingested if it is broken, cracked, or otherwise not intact.
Prior to the start and throughout treatment with the combination palbociclib plus fulvestrant, pre/perimenopausal women should be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to local clinical practice.
Dose modification of Ibrance is recommended based on individual safety and tolerability.
Management of some adverse reactions may require temporary dose interruptions/delays, and/or dose reductions, or permanent discontinuation as per dose reduction schedules provided in Tables 1-3 below (same as Tables 6, 7 and 8 in Precautions and Adverse Effects in PI Attachment 1).
Table 1: Recommended dose modifications
Table 2: Dose modifications and management Haematologic toxicities