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Oncotarget. 2019 Nov 5;10(60):6526-6535. doi: 10.18632/oncotarget.27251. eCollection 2019 Nov 5.

Efficacy and safety of buparlisib, a PI3K inhibitor, in patients with malignancies harboring a PI3K pathway activation: a phase 2, open-label, single-arm study.

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Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Division of Hematology & Medical Oncology, Oregon Health and Science University, Portland, OR, USA.
Department of Hematology & Oncology, Florida Cancer Specialists & Research Institute, West Palm Beach, FL, USA.
Division of Hematology & Oncology, The West Clinic, Memphis, TN, USA.
Department of Oncology, Highlands Oncology Group, Fayetteville, AR, USA.
Department of Drug Development, Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN, USA.
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
Department of Medical Oncology, US Oncology Research and Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA.


Background: Phosphatidylinositol 3-kinase (PI3K) pathway activation plays a key role in tumorigenesis and has been associated with poor prognosis and resistance to multiple therapies in various cancers. Results: There were 146 patients enrolled; common tumor types were colorectal, sarcoma, and ovarian. Tumors had PI3K pathway alterations and a median of four mutations with tissue-specific patterns of mutation burden (lowest: sarcoma [2.5]; highest: esophagus, germ cell tumor, skin non-melanoma, vaginal [7]). The number of prior therapies did not correlate with the number of genetic alterations (Pearson r = -0.037). The clinical benefit rate was 15.1% (n = 22). An additional patient had an unconfirmed complete response. The most common adverse events were fatigue, nausea, hyperglycemia, decreased appetite, and diarrhea. Patient and Methods: In this phase 2, open-label, single-arm study, patients with solid or hematologic malignancies with PI3K pathway activation and progression on or after standard treatment received buparlisib (100 mg once daily). The primary endpoint was clinical benefit rate per local investigator assessment (response or stable disease at ≥16 weeks). Conclusions: Buparlisib was well tolerated, however efficacy was limited despite selection of PI3K pathway aberrations. Future studies may provide insight into buparlisib efficacy by refining the molecular selection of different tumor types.


advanced malignancies; buparlisib; molecular selection; phosphatidylinositol 3-kinase pathway; tissue agnostic

Conflict of interest statement

CONFLICTS OF INTEREST S.A. Piha-Paul reports receiving research funding for their institution from AbbVie, Curis, Five Prime Therapeutics, Genmab, GSK, Helix Pharma, Incyte, MedImmune, Merck, NewLink Genetics, Novartis, Pfizer, Pieris, Principia Biopharma, Puma Biotechnology, Tesaro, and XuanZhu Pharma. M.H. Taylor reports receiving honoraria from ArQule, Array Biopharma, Blue Print Medicines, Bristol-Myers Squibb, Eisai Inc., Loxo Oncology, Trillium, and Novartis; consultancy/advisory role for ArQule, Array Biopharma, Blue Print Medicines, Bristol-Myers Squibb, Eisai Inc., Loxo Oncology, and Novartis; speakers’ bureau participation for Bristol-Myers Squibb and Eisai Inc.; and travel, accommodations, or expenses from Array Biopharma, Blue Print Medicines, Bristol-Myers Squibb, Eisai Inc., Loxo Oncology, and Novartis. D. Spitz reports research funding from Florida Cancer Specialists/Sarah Cannon Research. L. Schwartzberg reports consulting/advisory role for Helsinn, Heron, Merck, and Tesaro, and research funding from Helsinn. J.T. Beck reports no potential conflicts of interest to disclose. T.M. Bauer reports consultancy/advisory role for Guardant Health, Ignyta, Loxo Oncology, Moderna Therapeutics, and Pfizer; and receiving research funding for their institution from AbbVie, Aileron Therapeutics, Amgen, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Daiichi Sankyo, Deciphera, Five Prime Therapeutics, Genentech, GlaxoSmithKline, Ignyta, Immunocore, Immunogen, Incyte, Jacobio, Kolltan Pharmaceuticals, Leap Therapeutics, Lilly, MabVax, MedImmune, Medpacto Inc., Merck, Merrimack, Millennium, Mirati Therapeutics, Moderna Therapeutics, Novartis, Pfizer, Principa Biopharma, Peleton, Roche, Sanofi, and Stemline Therapeutics. F. Meric-Bernstam reports consulting role for Aduro BioTech, Dialectica, Jackson Laboratory, OrigiMed, Pieris, Samsung Bioepis, Sumitomo Dianippon, and Xencor; advisory role for Clearlight Diagnostics, Darwin Health, GRAIL, Inflection Biosciences, Mersana, and Spectrum; receiving research funding from AbbVie, Aileron, AstraZeneca, Bayer, Calithera Biosciences, Curis, CytomX, Daiichi Sankyo, eFFECTOR, Guardant Health, Jounce, Novartis, Millennium, Puma Biotechnology, Takeda, and Zymeworks; and travel, accommodations, or expenses from Debiopharm Group, Genentech, Pfizer, and Taiho. D. Purkayastha, L. Karpiak, and S. Szpakowski report employment by, and stock ownership of Novartis. S. Szpakowski reports employment of an immediate family member by Compass Therapeutics. F. Braiteh reports receiving honoraria from Amgen, AstraZeneca, Bristol-Myers Squibb, Genentech, Incyte, Merck, and Pfizer; consulting/advisory role for Amgen, AstraZeneca, Eisai, Exelixis, Genentech, and Pfizer; speakers’ bureau participation for Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Genentech, Incyte, Lilly, Pfizer, and Puma Biotechnology; and travel, accommodations, or expenses from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene, Eisai, Exelixis, Genentech, Incyte, Lilly, Pfizer, and Puma Biotechnology.

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