The FDA has granted accelerated approval for Pfizer's Ibrance (palbociclib), in combination with letrozole, for the treatment of postmenopausal women with estrogen receptor-positive (ER+), receptor tyrosine-protein kinase erbB-2-negative (HER2-) advanced breast cancer as initial endocrine-based therapy for their metastatic disease. This indication is approved under accelerated approval based on progression-free survival (PFS), and continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial. The confirmatory phase III trial, PALOMA-2, is fully enrolled (ClinicalTrials.gov Identifier NCT01740427 http://clinicaltrials.gov/ct2/show/NCT01740427).
Ibrance, reviewed under the FDA's breakthrough therapy and priority review programs, is the first cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor to be approved by the agency. It is available to order immediately through select specialty pharmacies. The NDA was based on the final results of the phase II trial PALOMA-1, which achieved its primary endpoint by demonstrating that palbociclib in combination with letrozole prolonged PFS compared with letrozole alone in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer who had not received previous systemic treatment for their advanced disease (ClinicalTrials.gov Identifier NCT00721409 http://clinicaltrials.gov/ct2/show/NCT00721409).
For women treated with the combination of palbociclib plus letrozole, the median PFS was 20.2 months, a substantial improvement compared to the 10.2 months of PFS in women who received letrozole alone. Overall response rate in patients with measurable disease as assessed by the investigator was higher in the palbociclib plus letrozole compared to the letrozole alone arm (55.4% versus 39.4%). The most frequently reported adverse event for palbociclib plus letrozole was neutropenia (Pfizer News Release; FDA News Release).
For a review of palbociclib, see Haddley, K. Drugs Fut 2013, 38(11): 745 https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=2076501&p_IsPs=N .