title: Pictilisib PI3Kinase inhibitor (a phosphatidylinositol 3-kinase [PI3K] inhibitor) plus paclitaxel for the treatment of hormone receptor-positive, HER2-negative, locally recurrent, or metastatic breast cancer: interim analysis of the multicentre, placebo-controlled, phase II randomised PEGGY study.
abstract: 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.
  
  
  
  One hundred and eighty-three eligible patients were randomised (1:1) to receive paclitaxel (90 mg/m2weekly 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  NCT01740336.
authors: Department of Medical Oncology, Université Catholique de Louvain, CHU UCL Namur, Sainte-Elisabeth peter.vuylsteke@cmsenamur.be.
authors: P
authors: P
authors: Vuylsteke
authors: Multidisciplinary Breast and Gynaecological Oncology Unit, Universitair Ziekenhuis Antwerpen, Antwerp, Belgium.
authors: M
authors: M
authors: Huizing
authors: Department of Medical Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors: K
authors: K
authors: Petrakova
authors: Department of Medical Oncology, Barts Health NHS Trust and Barts Cancer Institute, Queen Mary University of London, London.
authors: R
authors: R
authors: Roylance
authors: Department of Oncology, The Royal Surrey County Hospital, Guildford.
authors: R
authors: R
authors: Laing
authors: Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors: S
authors: S
authors: Chan
authors: Department of Medical Oncology, Calvary Mater Hospital Newcastle, New South Wales, Australia.
authors: F
authors: F
authors: Abell
authors: Oncology Biomarker Development.
authors: S
authors: S
authors: Gendreau
authors: Product Development Oncology.
authors: I
authors: I
authors: Rooney
authors: BioOncology.
authors: D
authors: D
authors: Apt
authors: Product Development Biometrics Biostatistics Department, Genentech Inc., South San Francisco, USA.
authors: J
authors: J
authors: Zhou
authors: Product Development Oncology.
authors: S
authors: S
authors: Singel
authors: Kaiser Permanente, Northern California, Vallejo, CA, USA.
authors: L
authors: L
authors: Fehrenbacher
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007191:Indazoles / Q000008:administration & dosage*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D013449:Sulfonamides / Q000008:administration & dosage*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058534:Class I Phosphatidylinositol 3-Kinases; D007191:Indazoles; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D013449:Sulfonamides; C532162:2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human
keywords: HER2-negative; PI3K; PIK3CA; hormone receptor-positive; metastatic breast cancer; pictilisib