Phase-2 trial of palbociclib in adult patients with recurrent RB1-positive glioblastoma

Journal of Neuro-oncology
Jennie W TaylorMichael D Prados

Abstract

Alterations in the CDK4/6-RB signaling pathway are common causes of cell cycle dysregulation in many cancers, including glioblastoma. Palbociclib is an oral inhibitor of CDK4/6, which leads to phosphorylation of RB1 and cell-cycle arrest. We conducted a two-arm study evaluating efficacy and tissue pharmacokinetics/pharmacodynamics of palbociclib in patients with recurrent glioblastoma. Eligibility criteria included confirmation of RB1 proficiency by IHC; ≤ 3 relapses; KPS ≥ 60; no limit on prior treatments. Arm 1 received palbociclib for 7 days prior to indicated resection followed by adjuvant palbociclib. Arm 2 received palbociclib without resection. Primary objective was PFS6; secondary included toxicity, OS, and ORR. Exploratory aims included biomarker assessment and pharmacokinetic/pharmacodynamic effects in surgical patients. Total of 22 patients were enrolled; 6 on Arm 1 and 16 on Arm 2. Trial was stopped early secondary to lack of efficacy, with 95% of evaluable patients progressing within 6 months. Median PFS was 5.14 weeks (range 5 days-142 weeks) and median OS was 15.4 weeks (range 2-274 weeks). Two patients (10%) had related grade ≥ 3 AEs. In Arm 1, 5 patients had tissue concentrations of palbociclib felt to be suffi...Continue Reading

References

Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Mar 22, 2008·Neuro-oncology·Kathleen R LambornUNKNOWN North American Brain Tumor Consortium
Sep 6, 2008·Nature·UNKNOWN Cancer Genome Atlas Research Network
Dec 31, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Teri N KreislHoward A Fine
Feb 25, 2009·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Sep 2, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Henry S FriedmanTimothy Cloughesy
Apr 29, 2010·Current Oncology Reports·Patrick Y WenEudocia Quant
Dec 14, 2011·Journal of Neuropathology and Experimental Neurology·Patricia GoldhoffJoanna J Phillips
May 16, 2012·Proceedings of the National Academy of Sciences of the United States of America·Emmanuelle HuillardDavid H Rowitch
Feb 21, 2014·The New England Journal of Medicine·Mark R GilbertMinesh P Mehta
Feb 21, 2014·The New England Journal of Medicine·Olivier L ChinotTimothy Cloughesy
Dec 15, 2015·Cancer Discovery·Charles J SherrGeoffrey I Shapiro
Dec 14, 2016·The New England Journal of Medicine·Richard S FinnDennis J Slamon
Aug 17, 2017·Nature·Shom GoelJean J Zhao

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Citations

Jun 14, 2019·The Journal of Pharmacology and Experimental Therapeutics·M JoveC J Twelves
Apr 12, 2020·Journal of Cellular and Molecular Medicine·Yingxiao CaoYanhui Qi
May 24, 2020·Medicinal Research Reviews·Ge YanZhiqiang Li
May 22, 2020·The Oncologist·Enrique GrandeTeresa Alonso-Gordoa
May 24, 2020·Current Neurology and Neuroscience Reports·Elisa K LiuSylvia C Kurz
Aug 18, 2020·Science China. Life Sciences·Song-Yang WuYi-Zhou Jiang
May 28, 2019·Molecular Neurobiology·Olivia Morris-HanonGuillermo Agustín Videla-Richardson
Apr 16, 2020·Cancers·Vilashini RajaratnamShama Parveen Mirza
Jul 10, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·An-Chi TienNader Sanai
Dec 17, 2020·Frontiers in Neuroscience·Federica Di CintioGiuseppe Toffoli
Dec 31, 2020·Cancers·Cristina BirzuGiuseppe Lombardi
Mar 7, 2021·Cancers·Hong-My NguyenDipongkor Saha
Mar 27, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Lili MaoJun Guo
May 1, 2021·Cancers·Elisabete Cruz Da SilvaLaurence Choulier
Jul 3, 2021·Cancers·Alice RanjanJing Wu
Aug 8, 2021·Cancers·Vincenzo Di NunnoAlba Ariela Brandes
Aug 8, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·E PanagiotouE Kotteas
Jul 3, 2021·Current Treatment Options in Oncology·Gerald C WallaceJohn W Henson
Oct 31, 2021·Journal of Hematology & Oncology·Yang XunHua You
Dec 3, 2021·Expert Reviews in Molecular Medicine·Peng LiuAnke Brüning-Richardson

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