Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

被引:26
作者
Zhao, Shen [1 ,2 ,3 ]
Zhang, Zhonghan [1 ,2 ,3 ]
Zhan, Jianhua [2 ,3 ,4 ]
Zhao, Xin [5 ]
Chen, Xinru [1 ,2 ,3 ]
Xiao, Liyun [5 ]
Wu, Kui [5 ,6 ]
Ma, Yuxiang [2 ,3 ,7 ]
Li, Mengzhen [8 ]
Yang, Yunpeng [1 ,2 ,3 ]
Fang, Wenfeng [1 ,2 ,3 ]
Zhao, Hongyun [2 ,3 ,7 ]
Zhang, Li [1 ,2 ,3 ]
机构
[1] Sun Yat Sen Univ Canc Ctr, Dept Med Oncol, 651 Dongfeng East Rd, Guangzhou 510060, Peoples R China
[2] State Key Lab Oncol South China, Guangzhou, Peoples R China
[3] Collaborat Innovat Ctr Canc Med, Guangzhou, Peoples R China
[4] Sun Yat Sen Univ Canc Ctr, Dept Expt Res, Guangzhou, Peoples R China
[5] BGI Shenzhen, Shenzhen, Peoples R China
[6] BGI Shenzhen, Shenzhen Key Lab Genom, Guangdong Prov Key Lab Human Dis Genom, Shenzhen, Peoples R China
[7] Sun Yat Sen Univ Canc Ctr, Dept Clin Res, 651 Dongfeng East Rd, Guangzhou 510060, Peoples R China
[8] MyGene Diagnost Co Ltd, Guangzhou, Peoples R China
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
Precision oncology; Comprehensive genomic profiling; Genotype-matched therapies; Biomarker-selected trials; Non-small cell lung cancer; TARGETED THERAPY; OPEN-LABEL; ASSOCIATION;
D O I
10.1186/s12916-021-02089-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: With the identification of new targetable drivers and the recent emergence of novel targeted drugs, using comprehensive genomic profiling in lieu of the routine testing for classic drivers in the clinical care for advanced NSCLC has been increasingly advocated. However, the key assumption justifying this practice, that comprehensive genomic profiling could lead to effective anticancer therapies and improve patient outcomes, remains unproved. Methods: Comprehensive genomic profiling was prospectively applied in 1564 advanced NSCLC patients to identify potentially actionable genomic alterations. Patients were assigned to genotype-matched targeted therapies or nonmatched therapies based on the profiling results. Its utility in directing treatments was determined by the proportion of patients receiving genotype-matched targeted therapies and the proportion of patients being enrolled into genotype-matched clinical trials. Its impacts on patient outcomes were assessed by comparing progression-free survival (PFS) and overall survival (OS) between patients who received a genotype-matched and nonmatched therapy. Results: From October 2016 to October 2019, tumor genomic profiles were established in 1166 patients, leading to a matched targeted therapy in 37.7% (n = 440) and a genotype-matched trial enrollment in 20.9% of patients (n = 244). Potentially actionable alterations were detected in 781 patients (67.0%). For these patients, a genomic profiling-directed matched therapy significantly improved PFS (9.0 months vs 4.9 months, P < 0.001) and OS (3.9 years vs 2.5 years, P < 0.001) compared with a nonmatched therapy. Excluding patients with standard targeted therapies, genomic profiling led to a matched targeted therapy in 16.7% (n = 24) and a matched trial enrollment in 11.2% (n = 16) of patients. No PFS (4.7 months vs 4.6 months, P = 0.530) or OS (1.9 years vs 2.4 years, P = 0.238) benefit was observed with the use of genotype-matched targeted therapies in this population. Conclusions: Comprehensive genomic profiling is of clinical utility in assisting treatment selection, facilitating clinical trial enrollment, and improving patient outcomes in advanced NSCLC. However, for patients carrying alterations without standard-of-care targeted drugs, the interpretation of genomic profiling results should be careful given the low likelihood of benefit from the investigational or off-label use of targeted therapies in this population in the current treatment landscape.
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页数:10
相关论文
共 26 条
[1]  
[Anonymous], 2018, Cancer Discov, V8, P1201, DOI 10.1158/2159-8290.CD-NB2018-116
[2]  
Chakravarty Debyani, 2017, JCO Precis Oncol, V2017, DOI 10.1200/PO.17.00011
[3]   Emerging therapeutic agents for advanced non-small cell lung cancer [J].
Chen, Ruqin ;
Manochakian, Rami ;
James, Lauren ;
Azzouqa, Abdel-Ghani ;
Shi, Huashan ;
Zhang, Yan ;
Zhao, Yujie ;
Zhou, Kexun ;
Lou, Yanyan .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2020, 13 (01)
[4]   Mastering the Complex Targeted Therapy for Non-small Cell Lung Cancer [J].
Devarakonda, Siddhartha ;
Govindan, Ramaswamy ;
Morgensztern, Daniel .
CANCER CELL, 2020, 38 (03) :320-322
[5]   Efficacy of Selpercatinib in RET Fusion-Positive Non-Small-Cell Lung Cancer [J].
Drilon, A. ;
Oxnard, G. R. ;
Tan, D. S. W. ;
Loong, H. H. F. ;
Johnson, M. ;
Gainor, J. ;
McCoach, C. E. ;
Gautschi, O. ;
Besse, B. ;
Cho, B. C. ;
Peled, N. ;
Weiss, J. ;
Kim, Y. -J. ;
Ohe, Y. ;
Nishio, M. ;
Park, K. ;
Patel, J. ;
Seto, T. ;
Sakamoto, T. ;
Rosen, E. ;
Shah, M. H. ;
Barlesi, F. ;
Cassier, P. A. ;
Bazhenova, L. ;
De Braud, F. ;
Garralda, E. ;
Velcheti, V. ;
Satouchi, M. ;
Ohashi, K. ;
Pennell, N. A. ;
Reckamp, K. L. ;
Dy, G. K. ;
Wolf, J. ;
Solomon, B. ;
Falchook, G. ;
Ebata, K. ;
Nguyen, M. ;
Nair, B. ;
Zhu, E. Y. ;
Yang, L. ;
Huang, X. ;
Olek, E. ;
Rothenberg, S. M. ;
Goto, K. ;
Subbiah, V. .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (09) :813-824
[6]   Non-Small Cell Lung Cancer, Version 1.2020 Featured Updates to the NCCN Guidelines [J].
Ettinger, David S. ;
Wood, Douglas E. ;
Aggarwal, Charu ;
Aisner, Dara L. ;
Akerley, Wallace ;
Bauman, Jessica R. ;
Bharat, Ankit ;
Bruno, Debora S. ;
Chang, Joe Y. ;
Chirieac, Lucian R. ;
D'Amico, Thomas A. ;
Dilling, Thomas J. ;
Dobelbower, Michael ;
Gettinger, Scott ;
Govindan, Ramaswamy ;
Gubens, Matthew A. ;
Hennon, Mark ;
Horn, Leora ;
Lackner, Rudy P. ;
Lanuti, Michael ;
Leal, Ticiana A. ;
Lin, Jules ;
Loo, Billy W., Jr. ;
Martins, Renato G. ;
Otterson, Gregory A. ;
Patel, Sandip P. ;
Reckamp, Karen L. ;
Riely, Gregory J. ;
Schild, Steven E. ;
Shapiro, Theresa A. ;
Stevenson, James ;
Swanson, Scott J. ;
Tauer, Kurt W. ;
Yang, Stephen C. ;
Gregory, Kristina ;
Hughes, Miranda .
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK, 2019, 17 (12) :1464-1472
[7]   Comprehensive Genomic Profiling Identifies Novel Genetic Predictors of Response to Anti-PD-(L)1 Therapies in Non-Small Cell Lung Cancer [J].
Fang, Wenfeng ;
Ma, Yuxiang ;
Yin, Jiani C. ;
Hong, Shaodong ;
Zhou, Huaqiang ;
Wang, Ao ;
Wang, Fufeng ;
Bao, Hua ;
Wu, Xue ;
Yang, Yunpeng ;
Huang, Yan ;
Zhao, Hongyun ;
Shao, Yang W. ;
Zhang, Li .
CLINICAL CANCER RESEARCH, 2019, 25 (16) :5015-5026
[8]   Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies [J].
Jordan, Emmet J. ;
Kim, Hyunjae R. ;
Arcila, Maria E. ;
Barron, David ;
Chakravarty, Debyani ;
Gao, JianJiong ;
Chang, Matthew T. ;
Ni, Andy ;
Kundra, Ritika ;
Jonsson, Philip ;
Jayakumaran, Gowtham ;
Gao, Sizhi Paul ;
Johnsen, Hannah C. ;
Hanrahan, Aphrothiti J. ;
Zehir, Ahmet ;
Rekhtman, Natasha ;
Ginsberg, Michelle S. ;
Li, Bob T. ;
Yu, Helena A. ;
Paik, Paul K. ;
Drilon, Alexander ;
Hellmann, Matthew D. ;
Reales, Dalicia N. ;
Benayed, Ryma ;
Rusch, Valerie W. ;
Kris, Mark G. ;
Chaft, Jamie E. ;
Baselga, Jose ;
Taylor, Barry S. ;
Schultz, Nikolaus ;
Rudin, Charles M. ;
Hyman, David M. ;
Berger, Michael F. ;
Solit, David B. ;
Ladanyi, Marc ;
Riely, Gregory J. .
CANCER DISCOVERY, 2017, 7 (06) :596-609
[9]   Molecular Testing Guideline for the Selection of Patients With Lung Cancer for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update [J].
Kalemkerian, Gregory P. ;
Narula, Navneet ;
Kennedy, Erin B. ;
Biermann, William A. ;
Donington, Jessica ;
Leighl, Natasha B. ;
Lew, Madelyn ;
Pantelas, James ;
Ramalingam, Suresh S. ;
Reck, Martin ;
Saqi, Anjali ;
Simoff, Michael ;
Singh, Navneet ;
Sundaram, Baskaran .
JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (09) :911-+
[10]   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