@article{a896bc5ea5264b7ea2542efbbae3d567,
title = "Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and Progressive Glioblastoma",
abstract = "Purpose: Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generationsequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma. Experimental Design: We conducted a prospective genomicsinformed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome sequencing and tumor RNA sequencing were performed to identify molecular targets for potential matched therapy. A multidisciplinary molecular tumor board issued treatment recommendations based on the genomic results, blood-brain barrier penetration of the indicated therapies, drug-drug interactions, and drug safety profiles. Feasibility of generating genomics-informed treatment recommendations within 35 days of surgery was assessed. Results: Of the 20 patients enrolled in the study, 16 patients had sufficient tumor tissue for analysis. Exome sequencing was completed for all patients, and RNA sequencing was completed for 14 patients. Treatment recommendations were provided within the study's feasibility time frame for 15 of 16 (94%) patients. Seven patients received treatment based on the tumor board recommendations. Two patients reached 12-month progression-free survival, both adhering to treatments based on the molecular profiling results. One patient remained on treatment and progression free 21 months after surgery, 3 times longer than the patient's previous time to progression. Analysis of matched nonenhancing tissue from 12 patients revealed overlapping as well as novel putatively actionable genomic alterations. Conclusions: Use of genome-wide molecular profiling is feasible and can be informative for guiding real-time, central nervous system-penetrant, genomics-informed treatment recommendations for patients with recurrent glioblastoma.",
author = "Byron, {Sara A.} and Tran, {Nhan L.} and Halperin, {Rebecca F.} and Phillips, {Joanna J.} and Kuhn, {John G.} and {De Groot}, {John F.} and Howard Colman and Ligon, {Keith L.} and Wen, {Patrick Y.} and Cloughesy, {Timothy F.} and Mellinghoff, {Ingo K.} and Butowski, {Nicholas A.} and Taylor, {Jennie W.} and Clarke, {Jennifer L.} and Chang, {Susan M.} and Berger, {Mitchel S.} and Molinaro, {Annette M.} and Maggiora, {Gerald M.} and Sen Peng and Sara Nasser and Liang, {Winnie S.} and Trent, {Jeffrey M.} and Berens, {Michael E.} and Carpten, {John D.} and Craig, {David W.} and Prados, {Michael D.}",
note = "Funding Information: The authors are grateful to the Ben and Catherine Ivy Foundation for funding this work. The authors wish to thank the patients who participated in this clinical study and their families. They also wish to thank Anny Shai (UCSF) and Shauna O'Connell (UCSF) for their assistance in this project, as well as the clinical research nurses and clinical research coordinators at UCSF and TGen who supported this study, including Jane Rabbitt (UCSF), Thelma Munoz (UCSF), Rajath Ramakrishna (UCSF), Jose Ramirez (TGen), and Carly Benford (TGen). Lastly, the authors thank the staff at Ashion and the Collaborative Sequencing Core at TGen for help with the clinical and research sequencing studies, respectively. Funding Information: J.F. de Groot is a consultant/advisory board member for AbbVie, AstraZeneca, CarThera, Celldex, Deciphera, DSMB:VBL Therapeutics, Eli Lilly, EMD-Serono, Five Prime Therapeutics, Foundation Medicine, Genentech, GW Pharmaceuticals, Insys Therapeutics, Kadmon, Merck, Mundipharma, Novartis, Novella, Novogen, Sanofi-Aventis, and Ziopharm. H. Colman reports receiving commercial research grants from DNAtrix, Kadmon, Merck, NewLink Genetics, Orbus, and Plexxikon, and is a consultant/advisory board member for AbbVie, CytRx, Genentech, Insys, Novocure, Omniox, OXiGENE, Roche, and Upsher-Smith. K.L. Ligon holds ownership interest (including patents) in Dana-Farber Cancer Institute and Travera LLC. T.F. Cloughesy is an employee of Agile Research Foundation, and is a consultant/advisory board member for AbbVie, Alexion, Boston Biomedical, Bristol-Myers Squibb, Cortice, GW Pharmaceuticals, Human Longevity, Insys, Merck, Novogen, Roche, Sunovion, Tocagen, VBL, and Wellcome Trust. J.W. Taylor is a consultant/advisory board member for Novocure. S.M. Chang is a consultant/advisory board member for Agios, Neuro-Onc, and Tocagen. No potential conflicts of interest were disclosed by the other authors. Publisher Copyright: {\textcopyright} 2017 AACR.",
year = "2018",
month = jan,
day = "15",
doi = "10.1158/1078-0432.CCR-17-0963",
language = "English (US)",
volume = "24",
pages = "295--305",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "2",
}