Palbociclib in Metastatic Breast Cancer

Indications and Patient Population

The American Society of Clinical Oncology recommends palbociclib in combination with letrozole as a first-line therapy for postmenopausal patients with metastatic breast cancer that is ER-positive and HER2-negative, with a 10-month improvement in progression-free survival compared to endocrine therapy alone 1, 2
For premenopausal patients, palbociclib can be used with an aromatase inhibitor and an LHRH agonist for ovarian suppression 1, 3, 4
The National Comprehensive Cancer Network recommends avoiding the use of palbociclib in patients who relapse less than 12 months after completing adjuvant therapy with an aromatase inhibitor 1, 3

The combination of palbociclib and letrozole (PALOMA-2) resulted in a median progression-free survival of 24.8 months vs 14.5 months with letrozole alone, with a hazard ratio of 0.58 (95% CI: 0.46-0.72) 1, 2, 3
The combination of palbociclib and fulvestrant (PALOMA-3) resulted in a 4.9-month improvement in progression-free survival compared to fulvestrant alone, with a hazard ratio of 0.46 (95% CI: 0.36-0.59) 1, 3
The objective response rate was 42% vs 35% with palbociclib and letrozole compared to letrozole alone 2

The recommended dose of palbociclib is 125 mg orally once daily for 21 days, followed by 7 days off (28-day cycle) 5, 6
Palbociclib should be administered with food to reduce variability and improve absorption in patients with low absorption 5, 6

The National Comprehensive Cancer Network recommends monitoring complete blood counts on day 1, 14, and 28 for the first two cycles, and then on day 1 of each subsequent cycle if no significant neutropenia occurs 5
Grade 3-4 neutropenia (ANC <1000/mm³) should be managed by delaying palbociclib until ANC ≥1500/mm³, and then resuming at the original dose or reducing the dose if necessary 5
Growth factors can be used for resistant neutropenia 5

Neutropenia grade 3-4 occurred in 54-62% of patients, and leukopenia grade 3-4 occurred in 19-25% of patients 2, 5
Febrile neutropenia was rare (<2%) and can be managed with standard supportive care 5
Common non-hematologic adverse events included fatigue (37.4%), nausea (35.1%), and alopecia grade 1-2 (32.9%) 2