PMID- 27573562 OWN - NLM STAT- MEDLINE DCOM- 20171226 LR - 20200206 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 27 IP - 11 DP - 2016 Nov TI - 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. PG - 2059-2066 AB - 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/m(2) 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. CI - (c) The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Vuylsteke, P AU - Vuylsteke P AD - Department of Medical Oncology, Universite Catholique de Louvain, CHU UCL Namur, Sainte-Elisabeth peter.vuylsteke@cmsenamur.be. FAU - Huizing, M AU - Huizing M AD - Multidisciplinary Breast and Gynaecological Oncology Unit, Universitair Ziekenhuis Antwerpen, Antwerp, Belgium. FAU - Petrakova, K AU - Petrakova K AD - Department of Medical Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic. FAU - Roylance, R AU - Roylance R AD - Department of Medical Oncology, Barts Health NHS Trust and Barts Cancer Institute, Queen Mary University of London, London. FAU - Laing, R AU - Laing R AD - Department of Oncology, The Royal Surrey County Hospital, Guildford. FAU - Chan, S AU - Chan S AD - Department of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK. FAU - Abell, F AU - Abell F AD - Department of Medical Oncology, Calvary Mater Hospital Newcastle, New South Wales, Australia. FAU - Gendreau, S AU - Gendreau S AD - Oncology Biomarker Development. FAU - Rooney, I AU - Rooney I AD - Product Development Oncology. FAU - Apt, D AU - Apt D AD - BioOncology. FAU - Zhou, J AU - Zhou J AD - Product Development Biometrics Biostatistics Department, Genentech Inc., South San Francisco, USA. FAU - Singel, S AU - Singel S AD - Product Development Oncology. FAU - Fehrenbacher, L AU - Fehrenbacher L AD - Kaiser Permanente, Northern California, Vallejo, CA, USA. LA - eng SI - ClinicalTrials.gov/NCT01740336 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20160829 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Indazoles) RN - 0 (Sulfonamides) RN - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.137 (PIK3CA protein, human) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Adult MH - Aged MH - Antibodies, Monoclonal, Humanized/administration & dosage MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage MH - Breast Neoplasms/*drug therapy/genetics/pathology MH - Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors/*genetics MH - Disease-Free Survival MH - Female MH - Humans MH - Indazoles/*administration & dosage MH - Middle Aged MH - Neoplasm Metastasis MH - Neoplasm Recurrence, Local/*drug therapy/genetics/pathology MH - Paclitaxel/administration & dosage MH - Receptor, ErbB-2/genetics MH - Sulfonamides/*administration & dosage OTO - NOTNLM OT - HER2-negative OT - PI3K OT - PIK3CA OT - hormone receptor-positive OT - metastatic breast cancer OT - pictilisib EDAT- 2016/10/30 06:00 MHDA- 2017/12/27 06:00 CRDT- 2016/08/31 06:00 PHST- 2016/03/02 00:00 [received] PHST- 2016/07/30 00:00 [accepted] PHST- 2016/10/30 06:00 [pubmed] PHST- 2017/12/27 06:00 [medline] PHST- 2016/08/31 06:00 [entrez] AID - S0923-7534(19)35837-5 [pii] AID - 10.1093/annonc/mdw320 [doi] PST - ppublish SO - Ann Oncol. 2016 Nov;27(11):2059-2066. doi: 10.1093/annonc/mdw320. Epub 2016 Aug 29.