FDA Approval of Palbociclib in Combination with Fulvestrant for the Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer

Clin Cancer Res. 2016 Oct 15;22(20):4968-4972. doi: 10.1158/1078-0432.CCR-16-0493. Epub 2016 Jul 12.

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Drug Approval*
  • Estradiol / adverse effects
  • Estradiol / analogs & derivatives*
  • Estradiol / therapeutic use
  • Female
  • Fulvestrant
  • Humans
  • Middle Aged
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism

Substances

  • Antineoplastic Agents, Hormonal
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyridines
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Fulvestrant
  • Estradiol
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • palbociclib