Abstract
Buparlisib is an orally available pan-Class I PI3K inhibitor, that is more potent than idelalisib in vitro. Its distinct toxicities include hyperglycemia, hypertension, and mood disturbance. IND216 is a single arm phase II trial of buparlisib in Relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Fourteen patients were enrolled, 13 were evaluable for response and toxicity. Six of 13 patients had a partial response (46%) with a median duration of response of 15.5 months, all 11 patients with tumor assessment experienced tumor shrinkage. The most common adverse events (≥15%) were hyperglycemia, fatigue, anxiety, and gastrointestinal toxicities; all were < grade 3 except for fatigue. Three patients stopped therapy for alterations in mood. Lower levels of raptor were significantly associated with greater tumor shrinkage, suggesting that raptor could be a biomarker for response. This requires further validation in a larger CLL patient cohort. The clinical activity of buparlisib is comparable to other phosphatidylinositol-3-kinase inhibitors, with a different toxicity profile.Novelty and impactBuparlisib, an oral, pan PI3 kinase inhibitor, is associated with a 46% partial response rate among patients with relapse chronic ly...Continue Reading
References
Jan 25, 2008·Blood·Michael HallekUNKNOWN International Workshop on Chronic Lymphocytic Leukemia
Mar 26, 2009·Blood·Matthias NiedermeierJan A Burger
Jun 5, 2010·Blood·Sarah E M HermanAmy J Johnson
Dec 2, 2010·Cancer Chemotherapy and Pharmacology·Jonathan HebbLawrence Panasci
Nov 3, 2011·British Journal of Cancer·A SmithE Roman
Dec 14, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Johanna C BendellJosé Baselga
Jul 11, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bruce D ChesonThomas J Kipps
Dec 15, 2012·International Journal of Cancer. Journal International Du Cancer·Lilian AmreinLawrence Panasci
Jan 8, 2013·Urology·Oussama M DarwishVitaly Margulis
Apr 2, 2013·Oncogene·G S DuckerR S Warren
Sep 17, 2013·Blood Cancer Journal·V Martinez-MarignacR Aloyz
Dec 18, 2013·Oncotarget·Veronica L Martinez MarignacRaquel Aloyz
Jan 24, 2014·The New England Journal of Medicine·Richard R FurmanSusan M O'Brien
May 30, 2014·The New England Journal of Medicine·Jennifer A WoyachJohn C Byrd
Jun 3, 2014·The New England Journal of Medicine·John C ByrdUNKNOWN RESONATE Investigators
Apr 29, 2015·Leukemia·K BalakrishnanV Gandhi
Dec 8, 2015·The New England Journal of Medicine·Jan A BurgerUNKNOWN RESONATE-2 Investigators
Jun 22, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M DreylingP L Zinzani
Oct 4, 2017·Haematologica·Anas YounesWon Seog Kim
Oct 5, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Martin DreylingPier Luigi Zinzani
Dec 2, 2017·Blood·Ian W FlinnSteven Horwitz
Dec 11, 2017·The Lancet Oncology·Angelo Di LeoThomas Bachelot
Feb 2, 2018·PloS One·Philip EarwakerValentine M Macaulay
Mar 22, 2018·The New England Journal of Medicine·John F SeymourArnon P Kater
Jul 22, 2018·Blood·Ian W Flinn
Oct 6, 2018·Blood·Ian W FlinnStephan Stilgenbauer
Dec 7, 2018·The New England Journal of Medicine·Jennifer A WoyachJohn C Byrd
Dec 14, 2018·The Lancet Oncology·Carol MorenoIan W Flinn
Dec 26, 2018·Clinical Lymphoma, Myeloma & Leukemia·Bruce D ChesonMartin Dreyling
Aug 1, 2019·The New England Journal of Medicine·Tait D ShanafeltMartin Tallman