FDA approval: Palbociclib for the treatment of postmenopausal patients with estrogen receptor-positive, HER2-negative metastatic breast cancer

Julia A. Beaver, Laleh Amiri-Kordestani, Rosane Charlab, Wei Chen, Todd Palmby, Amy Tilley, Jeanne Fourie Zirkelbach, Jingyu Yu, Qi Liu, Liang Zhao, Joyce Crich, Xiao Hong Chen, Minerva Hughes, Erik Bloomquist, Shenghui Tang, Rajeshwari Sridhara, Paul G. Kluetz, Geoffrey Kim, Amna Ibrahim, Richard PazdurPatricia Cortazar

Research output: Contribution to journalArticlepeer-review

Abstract

On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2.

Original languageEnglish (US)
Pages (from-to)4760-4766
Number of pages7
JournalClinical Cancer Research
Volume21
Issue number21
DOIs
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'FDA approval: Palbociclib for the treatment of postmenopausal patients with estrogen receptor-positive, HER2-negative metastatic breast cancer'. Together they form a unique fingerprint.

Cite this