On March 31, 2017, the U.S. Food and Drug Administration granted regular approval to palbociclib (IBRANCE®, Pfizer Inc.) for the treatment of hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women.

FDA granted palbociclib accelerated approval in February 2015, in combination with letrozole for the treatment of estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine based therapy in postmenopausal women. FDA granted palbociclib regular approval in February 2016, in combination with fulvestrant for the treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in women with disease progression following endocrine therapy.

The current approval was based on data from an international, randomized, double-blind, placebo-controlled, clinical trial (PALOMA-2) that randomized 666 postmenopausal women (2:1) to palbociclib plus letrozole or placebo plus letrozole. Palbociclib 125 mg or placebo was administered orally once daily for 21 consecutive days, followed by 7 days off. Letrozole 2.5 mg was administered orally once daily. Treatment continued until disease progression or unacceptable toxicity. The median progression-free survival (PFS) was 24.8 months in the palbociclib plus letrozole arm and 14.5 months in the placebo plus letrozole arm (HR=0.576, 95% CI: 0.463, 0.718, p0.0001).>

Safety data was evaluated in 444 patients who received palbociclib plus letrozole. Neutropenia was the most frequently reported adverse reaction in PALOMA-2 with an incidence of 80%. The most common adverse reactions observed in 10% or more of patients taking palbociclib were neutropenia, infections, leukopenia, fatigue, nausea, alopecia, stomatitis, diarrhea, anemia, rash, asthenia, thrombocytopenia, vomiting, decreased appetite, dry skin, pyrexia, and dysgeusia. The most frequently reported grade 3 or greater adverse reactions in patients receiving palbociclib plus letrozole were neutropenia, leukopenia, infections, and anemia. The palbociclib prescribing information recommends monitoring complete blood counts prior to starting therapy and at the beginning of each cycle, as well as on day 15 of the first 2 cycles.

In combination with an aromatase inhibitor or fulvestrant, the recommended palbociclib dose is a 125 mg capsule taken orally once daily with food for 21 consecutive days followed by 7 days off treatment. Please refer to the full prescribing information for the dose and schedule recommendation for the aromatase inhibitor or fulvestrant.

Full prescribing information for palbociclib is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207103s004lbl.pdf

FDA granted this application Priority Review and Breakthrough Therapy Designation. FDA approved this action approximately one month ahead of the goal date. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).