Palbociclib in hormone-receptor–positive advanced breast cancer

BackgroundGrowth of hormone-receptor–positive breast cancer is dependent on cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), which promote progression from the G1 phase to the S phase of the cell cycle. We assessed the efficacy of palbociclib (an inhibitor of CDK4 and CDK6) and fulvestrant in advanced breast cancer.MethodsThis phase 3 study involved 521 patients with advanced hormone-receptor–positive, human epidermal growth factor receptor 2–negative breast cancer that had relapsed or progressed during prior endocrine therapy. We randomly assigned patients in a 2:1 ratio to receive palbociclib and fulvestrant or placebo and fulvestrant. Premenopausal or perimenopausal women also received goserelin. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, objective response, rate of clinical benefit, patient-reported outcomes, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 195 events of disease progression or death had occurred.ResultsThe median progression-free survival was 9.2 months (95% confidence interval [CI], 7.5 to not estimable) with palbociclib–fulvestrant and 3.8 months (95% CI, 3.5 to 5.5) with placebo–fulvestrant (hazard ratio for disease progression or death, 0.42; 95% CI, 0.32 to 0.56; P<0.001). The most common grade 3 or 4 adverse events in the palbociclib–fulvestrant group were neutropenia (62.0%, vs. 0.6% in the placebo–fulvestrant group), leukopenia (25.2% vs. 0.6%), anemia (2.6% vs. 1.7%), thrombocytopenia (2.3% vs. 0%), and fatigue (2.0% vs. 1.2%). Febrile neutropenia was reported in 0.6% of palbociclib-treated patients and 0.6% of placebo-treated patients. The rate of discontinuation due to adverse events was 2.6% with palbociclib and 1.7% with placebo.ConclusionsAmong patients with hormone-receptor–positive metastatic breast cancer who had progression of disease during prior endocrine therapy, palbociclib combined with fulvestrant resulted in longer progression-free survival than fulvestrant alone. (Funded by Pfizer; PALOMA3 ClinicalTrials.gov number, NCT01942135.)

Who's Dean today? Acting and interim management as paradoxes of the contemporary university

Interim, discontinuous or 'acting' management is an increasingly ubiquitous feature of universities. This paper asks: What are the implications of this for good academic governance? Should we understand this managerial dance as a symptom of the collapse of good managerial order or, by contrast, as a symptom of the robustness and flexibility of the organisational culture of the university? Or both? This paper answers 'all of the above' to these questions. It reaches that conclusion by examining relevant literature, theorising a methodology for reading the field of interim management, and by applying this theorising to an analysis of qualitative data collected as part of a national collaborative research project conducted in Australia.

A data mining framework for electricity consumption analysis from meter data

This paper presents a novel data mining framework for the exploration and extraction of actionable knowledge from data generated by electricity meters. Although a rich source of information for energy consumption analysis, electricity meters produce a voluminous, fast-paced, transient stream of data that conventional approaches are unable to address entirely. In order to overcome these issues, it is important for a data mining framework to incorporate functionality for interim summarization and incremental analysis using intelligent techniques. The proposed Incremental Summarization and Pattern Characterization (ISPC) framework demonstrates this capability. Stream data is structured in a data warehouse based on key dimensions enabling rapid interim summarization. Independently, the IPCL algorithm incrementally characterizes patterns in stream data and correlates these across time. Eventually, characterized patterns are consolidated with interim summarization to facilitate an overall analysis and prediction of energy consumption trends. Results of experiments conducted using the actual data from electricity meters confirm applicability of the ISPC framework.