Palbociclib: A Novel Cyclin-Dependent Kinase Inhibitor for Hormone Receptor–Positive Advanced Breast Cancer. (November 2015)

• Record Type: Journal Article
• Authors: Mangini, Neha S.; Wesolowski, Robert; Ramaswamy, Bhuvaneswari; Lustberg, Maryam B.; Berger, Michael J.
• Is Part Of: Annals of pharmacotherapy. Volume 49:Number 11(2015:Nov.)
• Page Start: 1252
• Page End: 1260
• Publication Date: 2015-11
• Subjects: palbociclib -- CDK inhibitor -- PD-0332991 -- letrozole -- fulvestrant -- advanced breast cancer; Chemotherapy -- Periodicals; Pharmacology -- Periodicals; 615.5805
• DOI: 10.1177/1060028015602273
• Languages: English
• ISSNs: 1060-0280

Abstract

Objective: To review palbociclib, a novel small-molecule inhibitor of cyclin-dependent kinases 4 and 6, and its current place in therapy for the treatment of hormone receptor (HMR)-positive, human epidermal growth factor receptor 2 (Her2)-negative advanced breast cancer.Study Selection and Data Abstraction: Four phase I trials, 2 phase II trials, and 1 phase III trial were identified from May 2004 to May 2015 using PubMed, American Society of Clinical Oncology (ASCO) abstracts, and European Society of Medical Oncology (ESMO) abstracts.Data Synthesis: In the first-line setting, the phase II PALbociclib: Ongoing trials in the Management of breast cAncer (PALOMA)-1 trial randomized patients to receive letrozole alone or letrozole plus palbociclib 125 mg daily for 3 weeks, followed by 1 week off, as initial therapy for advanced breast cancer. The investigator-assessed median progression-free survival (PFS) was 20. 2 months for the combination versus 10.2 months for letrozole alone (hazard ratio [HR] = 0.488; 95% CI = 0.319-0.748; 1-sided P = 0.0004). The ensuing Food and Drug Administration approval of palbociclib was given a "breakthrough therapy" designation, where preliminary evidence suggests substantial improvement over existing therapies for a serious or life-threatening disease. A confirmatory phase III trial, PALOMA-2, is under way. In patients who were previously treated with endocrine therapy for advanced breast cancer, the phase III PALOMA-3 trial randomized patients to fulvestrant plus palbociclib versus fulvestrant plus placebo. The investigator-assessed median PFS at the time of a preplanned analysis was 9.2 months with palbociclib-fulvestrant compared with 3.8 months with placebo-fulvestrant (HR = 0.42; 95% CI = 0.32-0.56; P < 0.001).Conclusions: Palbociclib, the first-in-class CDK4/6 inhibitor, significantly extended PFS in combination with endocrine therapy in the first and subsequent lines of treatment for HMR-positive, Her2-negative advanced breast cancer.