ABSTRACT
BACKGROUND: The objective of this study was to review the pharmacology, efficacy, and safety of palbociclib, a first-in-class cyclin-dependent kinase 4/6 inhibitor, for the management of advanced breast cancer (ABC). METHODS: Pharmacokinetics and drug interactions associated with palbociclib are described. Recent clinical trial data are reviewed, including patient-reported outcomes and subgroup analyses. RESULTS: Palbociclib is indicated in combination with an aromatase inhibitor as initial endocrine therapy (ET) or with fulvestrant for patients with disease progression following ET for hormone receptor positive, human epidermal growth factor receptor 2 negative ABC or metastatic breast cancer. Palbociclib inhibits cyclin-dependent kinases 4/6, resulting in a blockade of phosphorylation of the retinoblastoma protein, which hinders the activation of transcription factors involved in S-phase entry, thereby arresting cell cycle progression at G1 phase. The efficacy and safety of palbociclib in combination with ET was established in three randomized trials (PALOMA-1, -2, and -3); all studies met their primary endpoint of significantly prolonging investigator-assessed progression-free survival versus ET alone. Findings were similar in subgroup analyses of the three PALOMA studies. Palbociclib plus ET also maintained health-related quality of life (QoL) compared with ET alone in PALOMA-2 and -3. A long-term safety profile for palbociclib, up to 3 years, has been established. Neutropenia, the most common any-grade and grade 3 or higher adverse event associated with palbociclib, is consistent with the drug's mechanism of action and can be effectively managed with dose interruption, dose reduction, or delay in starting treatment cycles. CONCLUSIONS: Palbociclib in combination with ET improved progression-free survival and QoL in patients with ABC, including in several patient subgroups.
ABSTRACT
BACKGROUND: In the advent of generic statins becoming increasingly available and with the recent addition of atorvastatin to the generic market, healthcare providers are often encouraged by payers to switch from a branded statin to an alternate, less costly agent. OBJECTIVE: The aim of this study was to determine the impact of a therapeutic switch on cholesterol goal attainment among patients with existing cardiovascular disease (CVD) or risk factors for CVD. STUDY DESIGN: A cross-sectional, multisite retrospective review of patient records evaluating low-density lipoprotein cholesterol (LDL-C) control before and after switching statins was conducted. METHODS: Participants were 18 to 89 years olds who were stable on statin therapy and had 1 or more risk factors for CVD. Patients meeting switch criteria (n = 833) were evaluated for changes in their statin therapy and LDL-C goal attainment. Drug/dose information, cholesterol values, and goal attainment in accordance with National Cholesterol Education Panel Third Adult Treatment Panel guidelines were determined before and after the switch. Dose potency was based on mean LDL-C reductions. RESULTS: Data were collected from 22 US sites. Risk factors for CVD were common, with 88.5% of patients identified as high risk. Overall, patients' mean LDL-C levels improved from 87.1 to 81.5 mg/dL, and goal attainment increased from 75.5% to 82.5% (P < .05). Switches to a comparable or higher statin/dose improved mean LDL-C and goal attainment (P < .05). However, in patients transitioned to a lower statin/dose equivalency (36.4%), mean LDL-C level increased from 79.8 to 85.6 mg/dL and goal attainment fell from 84.2% to 78.6% (P < .05). Logistic regression confirmed that LDL-C goal attainment was reduced by 53% in patients switched to a lower statin/dose (odds ratio, 0.47; 95% confidence interval, 0.30-0.76; P = .002) compared with patients switched to an equipotent dose. The use of adjunctive lipid-lowering therapies increased in patients switched to a lower statin/dose (P < .05). CONCLUSIONS: Cholesterol values and goal attainment can be negatively impacted when a systematic approach is not used and patients are switched to lower potency therapies.
