FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.
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.
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland. Julia.Beaver@fda.hhs.gov.
Julia A
JA
Beaver
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Laleh
L
Amiri-Kordestani
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Rosane
R
Charlab
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Wei
W
Chen
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Todd
T
Palmby
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Amy
A
Tilley
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Jeanne Fourie
JF
Zirkelbach
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Jingyu
J
Yu
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Qi
Q
Liu
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Liang
L
Zhao
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Joyce
J
Crich
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Xiao Hong
XH
Chen
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Minerva
M
Hughes
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Erik
E
Bloomquist
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Shenghui
S
Tang
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Rajeshwari
R
Sridhara
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Paul G
PG
Kluetz
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Geoffrey
G
Kim
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Amna
A
Ibrahim
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Richard
R
Pazdur
Center for Drug Evaluation and Research, U.S. Food and Drug, Administration, White Oak, Maryland.
Patricia
P
Cortazar
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002986:Clinical Trials as Topic; D017277:Drug Approval; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D018579:Patient Selection; D010879:Piperazines / Q000627:therapeutic use*; D017698:Postmenopause; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012107:Research Design; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C500026:palbociclib