Feasibility of Large-Scale Genomic Testing to Facilitate Enrollment Onto Genomically Matched Clinical Trials

被引:332
作者
Meric-Bernstam, Funda [1 ]
Brusco, Lauren [1 ]
Shaw, Kenna [1 ]
Horombe, Chacha [1 ]
Kopetz, Scott [1 ]
Davies, Michael A. [1 ]
Routbort, Mark [1 ]
Piha-Paul, Sarina A. [1 ]
Janku, Filip [1 ]
Ueno, Naoto [1 ]
Hong, David [1 ]
De Groot, John [1 ]
Ravi, Vinod [1 ]
Li, Yisheng [1 ]
Luthra, Raja [1 ]
Patel, Keyur [1 ]
Broaddus, Russell [1 ]
Mendelsohn, John [1 ]
Mills, Gordon B. [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
BREAST-CANCER; GENERATION; VALIDATION;
D O I
10.1200/JCO.2014.60.4165
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose We report the experience with 2,000 consecutive patients with advanced cancer who underwent testing on a genomic testing protocol, including the frequency of actionable alterations across tumor types, subsequent enrollment onto clinical trials, and the challenges for trial enrollment. Patients and Methods Standardized hotspot mutation analysis was performed in 2,000 patients, using either an 11-gene (251 patients) or a 46- or 50-gene (1,749 patients) multiplex platform. Thirty-five genes were considered potentially actionable based on their potential to be targeted with approved or investigational therapies. Results Seven hundred eighty-nine patients (39%) had at least one mutation in potentially actionable genes. Eighty-three patients (11%) with potentially actionable mutations went on genotype-matched trials targeting these alterations. Of 230 patients with PIK3CA/AKT1/PTEN/BRAF mutations that returned for therapy, 116 (50%) received a genotype-matched drug. Forty patients (17%) were treated on a genotype-selected trial requiring a mutation for eligibility, 16 (7%) were treated on a genotype-relevant trial targeting a genomic alteration without biomarker selection, and 40 (17%) received a genotype-relevant drug off trial. Challenges to trial accrual included patient preference of noninvestigational treatment or local treatment, poor performance status or other reasons for trial ineligibility, lack of trials/slots, and insurance denial. Conclusion Broad implementation of multiplex hotspot testing is feasible; however, only a small portion of patients with actionable alterations were actually enrolled onto genotype-matched trials. Increased awareness of therapeutic implications and access to novel therapeutics are needed to optimally leverage results from broad-based genomic testing. (C) 2015 by American Society of Clinical Oncology
引用
收藏
页码:2753 / U61
页数:14
相关论文
共 10 条
[1]   Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER) [J].
Andre, Fabrice ;
Bachelot, Thomas ;
Commo, Frederic ;
Campone, Mario ;
Arnedos, Monica ;
Dieras, Veronique ;
Lacroix-Triki, Magali ;
Lacroix, Ludovic ;
Cohen, Pascale ;
Gentien, David ;
Adelaide, Jose ;
Dalenc, Florence ;
Goncalves, Anthony ;
Levy, Christelle ;
Ferrero, Jean-Marc ;
Bonneterre, Jacques ;
Lefeuvre, Claudia ;
Jimenez, Marta ;
Filleron, Thomas ;
Bonnefoi, Herve .
LANCET ONCOLOGY, 2014, 15 (03) :267-274
[2]   Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing [J].
Frampton, Garrett M. ;
Fichtenholtz, Alex ;
Otto, Geoff A. ;
Wang, Kai ;
Downing, Sean R. ;
He, Jie ;
Schnall-Levin, Michael ;
White, Jared ;
Sanford, Eric M. ;
An, Peter ;
Sun, James ;
Juhn, Frank ;
Brennan, Kristina ;
Iwanik, Kiel ;
Maillet, Ashley ;
Buell, Jamie ;
White, Emily ;
Zhao, Mandy ;
Balasubramanian, Sohail ;
Terzic, Selmira ;
Richards, Tina ;
Banning, Vera ;
Garcia, Lazaro ;
Mahoney, Kristen ;
Zwirko, Zac ;
Donahue, Amy ;
Beltran, Himisha ;
Mosquera, Juan Miguel ;
Rubin, Mark A. ;
Dogan, Snjezana ;
Hedvat, Cyrus V. ;
Berger, Michael F. ;
Pusztai, Lajos ;
Lechner, Matthias ;
Boshoff, Chris ;
Jarosz, Mirna ;
Vietz, Christine ;
Parker, Alex ;
Miller, Vincent A. ;
Ross, Jeffrey S. ;
Curran, John ;
Cronin, Maureen T. ;
Stephens, Philip J. ;
Lipson, Doron ;
Yelensky, Roman .
NATURE BIOTECHNOLOGY, 2013, 31 (11) :1023-+
[3]   Physicians' Attitudes About Multiplex Tumor Genomic Testing [J].
Gray, Stacy W. ;
Hicks-Courant, Katherine ;
Cronin, Angel ;
Rollins, Barrett J. ;
Weeks, Jane C. .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (13) :1317-+
[4]   Clinical Next-Generation Sequencing in Patients with Non-Small Cell Lung Cancer [J].
Hagemann, Ian S. ;
Devarakonda, Siddhartha ;
Lockwood, Christina M. ;
Spencer, David H. ;
Guebert, Kalin ;
Bredemeyer, Andrew J. ;
Al-Kateb, Hussam ;
Nguyen, TuDung T. ;
Duncavage, Eric J. ;
Cottrell, Catherine E. ;
Kulkarni, Shashikant ;
Nagarajan, Rakesh ;
Seibert, Karen ;
Baggstrom, Maria ;
Waqar, Saiama N. ;
Pfeifer, John D. ;
Morgensztern, Daniel ;
Govindan, Ramaswamy .
CANCER, 2015, 121 (04) :631-639
[5]   Enabling a Genetically Informed Approach to Cancer Medicine: A Retrospective Evaluation of the Impact of Comprehensive Tumor Profiling Using a Targeted Next-Generation Sequencing Panel [J].
Johnson, Douglas B. ;
Dahlman, Kimberly H. ;
Knol, Jared ;
Gilbert, Jill ;
Puzanov, Igor ;
Means-Powell, Julie ;
Balko, Justin M. ;
Lovly, Christine M. ;
Murphy, Barbara A. ;
Goff, Laura W. ;
Abramson, Vandana G. ;
Crispens, Marta A. ;
Mayer, Ingrid A. ;
Berlin, Jordan D. ;
Horn, Leora ;
Keedy, Vicki L. ;
Reddy, Nishitha M. ;
Arteaga, Carlos L. ;
Sosman, Jeffrey A. ;
Pao, William .
ONCOLOGIST, 2014, 19 (06) :616-622
[6]   Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs [J].
Kris, Mark G. ;
Johnson, Bruce E. ;
Berry, Lynne D. ;
Kwiatkowski, David J. ;
Iafrate, A. John ;
Wistuba, Ignacio I. ;
Varella-Garcia, Marileila ;
Franklin, Wilbur A. ;
Aronson, Samuel L. ;
Su, Pei-Fang ;
Shyr, Yu ;
Camidge, D. Ross ;
Sequist, Lecia V. ;
Glisson, Bonnie S. ;
Khuri, Fadlo R. ;
Garon, Edward B. ;
Pao, William ;
Rudin, Charles ;
Schiller, Joan ;
Haura, Eric B. ;
Socinski, Mark ;
Shirai, Keisuke ;
Chen, Heidi ;
Giaccone, Giuseppe ;
Ladanyi, Marc ;
Kugler, Kelly ;
Minna, John D. ;
Bunn, Paul A. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2014, 311 (19) :1998-2006
[7]   Routine Multiplex Mutational Profiling of Melanomas Enables Enrollment in Genotype-Driven Therapeutic Trials [J].
Lovly, Christine M. ;
Dahlman, Kimberly Brown ;
Fohn, Laurel E. ;
Su, Zengliu ;
Dias-Santagata, Dora ;
Hicks, Donna J. ;
Hucks, Donald ;
Berry, Elizabeth ;
Terry, Charles ;
Duke, MarKeesa ;
Su, Yingjun ;
Sobolik-Delmaire, Tammy ;
Richmond, Ann ;
Kelley, Mark C. ;
Vnencak-Jones, Cindy L. ;
Iafrate, A. John ;
Sosman, Jeffrey ;
Pao, William .
PLOS ONE, 2012, 7 (04)
[8]   Concordance of Genomic Alterations between Primary and Recurrent Breast Cancer [J].
Meric-Bernstam, Funda ;
Frampton, Garrett M. ;
Ferrer-Lozano, Jaime ;
Yelensky, Roman ;
Perez-Fidalgo, Jose A. ;
Wang, Ying ;
Palmer, Gary A. ;
Ross, Jeffrey S. ;
Miller, Vincent A. ;
Su, Xiaoping ;
Eroles, Pilar ;
Antonio Barrera, Juan ;
Burgues, Octavio ;
Lluch, Ana M. ;
Zheng, Xiaofeng ;
Sahin, Aysegul ;
Stephens, Philip J. ;
Mills, Gordon B. ;
Cronin, Maureen T. ;
Gonzalez-Angulo, Ana M. .
MOLECULAR CANCER THERAPEUTICS, 2014, 13 (05) :1382-1389
[9]  
Routbort M, 2012, J MOL DIAGN, V14, P747
[10]   Clinical Validation of a Next-Generation Sequencing Screen for Mutational Hotspots in 46 Cancer-Related Genes [J].
Singh, Rajesh R. ;
Patel, Keyur P. ;
Routbort, Mark J. ;
Reddy, Neelima G. ;
Barkoh, Bedia A. ;
Handal, Brian ;
Kanagal-Shamanna, Rashmi ;
Greaves, Wesley O. ;
Medeiros, L. Jeffrey ;
Aldape, Kenneth D. ;
Luthra, Rajyalakshmi .
JOURNAL OF MOLECULAR DIAGNOSTICS, 2013, 15 (05) :607-622