FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer

• Published in: Clinical cancer research 2015-11, Vol.21 (21), p.4760-4766
• Main Authors: Beaver, Julia A, Amiri-Kordestani, Laleh, Charlab, Rosane, Chen, Wei, Palmby, Todd, Tilley, Amy, Zirkelbach, Jeanne Fourie, Yu, Jingyu, Liu, Qi, Zhao, Liang, Crich, Joyce, Chen, Xiao Hong, Hughes, Minerva, Bloomquist, Erik, Tang, Shenghui, Sridhara, Rajeshwari, Kluetz, Paul G, Kim, Geoffrey, Ibrahim, Amna, Pazdur, Richard, Cortazar, Patricia
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Clinical Trials as Topic; Drug Approval; Female; Humans; Neoplasm Metastasis; Patient Selection; Piperazines - therapeutic use; Postmenopause; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Pyridines - therapeutic use; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Research Design; Treatment Outcome; United States; United States Food and Drug Administration
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-15-1185

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.