BACKGROUND: Approximately 40% of hormone receptor-positive, HER2-negative breast cancers (BCs) are associated with activating mutations of the phosphatidylinositol 3-kinase (PI3K) pathway. Pictilisib, a potent and highly specific class I pan-PI3K inhibitor, demonstrated preclinical activity in BC cell lines and may potentiate the effect of taxanes, benefiting patients with or without aberrant activation of the PI3K pathway. PEGGY (NCT01740336), a randomised, placebo-controlled phase II trial, examined whether pictilisib augments the anti-tumour activity of paclitaxel in patients with hormone receptor-positive, HER2-negative locally recurrent or metastatic BC (mBC). We report results from the protocol-specified interim analysis. PATIENTS AND METHODS: One hundred and eighty-three eligible patients were randomised (1:1) to receive paclitaxel (90 mg/m2 weekly for 3 weeks in every 28-day cycle) with either 260 mg pictilisib or placebo (daily on days 1-5 every week). The primary end point was progression-free survival (PFS) in the intention-to-treat (ITT) population and patients with PIK3CA-mutated tumours. Secondary end points included overall response rate (ORR), duration of response, and safety. RESULTS: In the ITT population, the median PFS was 8.2 months with pictilisib (n = 91) versus 7.8 months with placebo (n = 92) [hazard ratio (HR) for progression or death, 0.95; 95% confidence interval (CI) 0.62-1.46; P = 0.83]. In patients with PIK3CA-mutated tumours, the median PFS was 7.3 months for pictilisib (n = 32) versus 5.8 months with placebo (n = 30) (HR, 1.06; 95% CI 0.52-2.12; P = 0.88). ORR was similar between treatment arms. The safety profile of pictilisib was consistent with previous reports, with no new safety signals. Proportions of patients with grade ≥3 adverse events (AEs), serious AEs, and dose reductions/discontinuations due to AEs were higher with pictilisib. CONCLUSIONS: PEGGY did not meet its primary end point, revealing no significant benefit from adding pictilisib to paclitaxel for patients with hormone receptor-positive, HER2-negative locally recurrent or mBC. CLINICAL TRIAL NUMBER: NCT01740336.

BioOncology

Department of Clinical Oncology Nottingham University Hospitals NHS Trust Nottingham UK

Department of Medical Oncology Barts Health NHS Trust and Barts Cancer Institute Queen Mary University of London London

Department of Medical Oncology Calvary Mater Hospital Newcastle New South Wales Australia

Department of Medical Oncology Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Medical Oncology Université Catholique de Louvain CHU UCL Namur Sainte Elisabeth

Department of Oncology The Royal Surrey County Hospital Guildford

Kaiser Permanente Northern California Vallejo CA USA

Multidisciplinary Breast and Gynaecological Oncology Unit Universitair Ziekenhuis Antwerpen Antwerp Belgium

Oncology Biomarker Development

Product Development Biometrics Biostatistics Department Genentech Inc South San Francisco USA

Product Development Oncology

Citace poskytuje Crossref.org

Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK)

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01740336