title: FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer.
abstract: On February 19, 2016, the FDA approved palbociclib (Ibrance, Pfizer) for use in combination with fulvestrant (Faslodex, AstraZeneca) for the treatment of women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer (MBC) with disease progression following endocrine therapy. The approval was based on the results of a randomized, double-blind, placebo-controlled trial conducted in 521 pre- and postmenopausal women with HR-positive, HER2-negative advanced or MBC. Patients were randomized (2:1) to receive palbociclib plus fulvestrant (n = 347) or placebo plus fulvestrant (n = 174). The primary endpoint was investigator-assessed progression-free survival (PFS). A statistically significant and clinically meaningful improvement in PFS (9.5 months vs. 4.6 months) was observed in patients receiving palbociclib plus fulvestrant [HR 0.46; 95% confidence interval (CI), 0.36-0.59; P < 0.0001]. Safety data confirmed the known adverse reaction profile of palbociclib. The most common adverse reactions (>20%) in patients treated with palbociclib were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, and thrombocytopenia. This approval was granted in the context of a prior accelerated approval for palbociclib in combination with letrozole in patients with HR-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy. Clin Cancer Res; 22(20); 4968-72. ©2016 AACR.
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland. amanda.walker@fda.hhs.gov suparna.wedam@fda.hhs.gov.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Walker
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland. amanda.walker@fda.hhs.gov suparna.wedam@fda.hhs.gov.
authors.forename: Suparna
authors.initials: S
authors.lastname: Wedam
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Laleh
authors.initials: L
authors.lastname: Amiri-Kordestani
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Erik
authors.initials: E
authors.lastname: Bloomquist
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Shengui
authors.initials: S
authors.lastname: Tang
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Palmby
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Fourie Zirkelbach
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Wentao
authors.initials: W
authors.lastname: Fu
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Amy
authors.initials: A
authors.lastname: Tilley
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Kim
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Kluetz
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Amy E
authors.initials: AE
authors.lastname: McKee
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D017277:Drug Approval; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004958:Estradiol; D000077267:Fulvestrant; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human; C500026:palbociclib