On March 31, 2017, the U.S. Food and Drug Administration (FDA) granted palbociclib (IBRANCE) general approval for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine therapy in postmenopausal women.
In February 2015, the FDA granted accelerated approval to palbociclib in combination with an aromatase inhibitor (letrozole) for the treatment of estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine therapy in postmenopausal women. In February 2016, the FDA approved palbociclib in combination with fulvestrant for the treatment of HR-positive, HER2-negative, or metastatic breast cancer in women whose disease has progressed after endocrine therapy.
The current approval is based on data from an international, randomized, double-blind, placebo-controlled clinical trial (PALOMA-2), which randomized 666 postmenopausal women (2:1) to receive palbociclib plus letrozole or placebo plus letrozole. Palbociclib 125 mg or placebo was administered orally once daily for 21 consecutive days, followed by a 7-day rest period. Letrozole 2.5 mg was administered once daily. Treatment continued until disease progression or unacceptable toxicity. The median progression-free survival (PFS) was 24.8 months in the palbociclib + letrozole group and 14.5 months in the placebo + letrozole group (HR=0.576, 95% CI: 0.463, 0.718, p<0.0001). Overall survival data are not yet mature.
The safety of palbociclib in combination with the aromatase inhibitor letrozole was evaluated in 444 patients. Neutropenia is the most common adverse reaction in PALOMA-2, occurring in 80% of patients. The most common adverse reactions observed in patients taking palbociclib are neutropenia, infection, leukopenia, fatigue, nausea, alopecia, stomatitis, diarrhea, anemia, rash, asthenia, thrombocytopenia, vomiting, decreased appetite, dry skin, fever, and dysgeusia. In patients receiving palbociclib in combination with letrozole, the most common grade 3 or more serious adverse reactions are neutropenia, leukopenia, infection, and anemia. The palbociclib package insert recommends monitoring complete blood cell counts before starting treatment, at the start of each cycle, and on day 15 of the first two cycles.
When used in combination with an aromatase inhibitor (letrozole) or fulvestrant, the recommended palbociclib dosage is 125 mg capsules orally once daily for 21 days with food, followed by a 7-day break. For dosage and schedule recommendations for aromatase inhibitors or fulvestrant, please refer to the complete prescribing information. The above is the latest information regarding the safety of palbociclib in combination with the aromatase inhibitor letrozole for the treatment of breast cancer. For more information about palbociclib, please contact our pharmacist customer service.
