Emmet J. Jordan1,*, Hyunjae R. Kim6,*, Maria E. Arcila6, David Barron3, Debyani Chakravarty9, JianJiong Gao9, Matthew T. Chang2,7, Andy Ni7, Ritika Kundra 9, Philip Jonsson2,7, Gowtham Jayakumaran6, Sizhi Paul Gao2, Hannah C. Johnsen2, Aphrothiti J. Hanrahan2, Ahmet Zehir6, Natasha Rekhtman6, Michelle S. Ginsberg8, Bob T. Li4, Helena A. Yu4, Paul K. Paik4, Alexander Drilon4, Matthew D. Hellmann4, Dalicia N. Reales2, Ryma Benayed6, Valerie W. Rusch5, Mark G. Kris4, Jamie E. Chaft4, Jose Baselga1,2, Barry S. Taylor2,7,9, Nikolaus Schultz7,9, Charles M. Rudin4, David M. Hyman1, Michael F. Berger6,9, David B. Solit1,2,9, Marc Ladanyi2,6, Gregory J.Riely4
1 Department of Medicine, Memor ial Sloan Kettering Cancer Cent er, New York, NY, USA.
2 Human Oncology and Pathogenes is Program, Memorial Sloan Kettering Cancer Center, NY, USA.
3 Department of Radiation Oncology, Memorial Sloan Kettering C ancer Center, New York, NY, USA.
4 Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
5 Department of Surgery, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
6 Department of Pathology, Molecular Diagnostics Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
7 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
8 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
9 Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
*These authors contributed equally to this manuscript
Corresponding Authors : Dr Gregory J. Riely MD, Memorial Sloan Kettering Cancer Center, 1275 York Avenue,New York, NY, 10065
Tumor genetic testing is standard of care for patients with advanced lung adenocarcinoma but the fraction of patients who derive clinical benefit remains undefined. Here, we report the experience of 860 patients with metastatic lung adenocarcinoma analyzed prospectively for mutations in >300 cancer-associated genes. Potentially actionable genetic events were stratified into one of four levels based upon published clinical or laboratory evidence that the mutation in question confers increased sensitivity to standard or investigational therapies. Overall 37.1% (319/860) of patients received a matched therapy guided by their tumor molecular profile. Excluding alterations associated with standard of care therapy, 14.4% (69/478) received matched therapy with a clinical benefit of 52%. Use of matched therapy was strongly influenced by the level of pre-existent clinical evidence that the mutation identified predicts for drug response. Analysis of genes mutated significantly more often in tumors without known actionable mutations nominated STK11 and KEAP1 as possible targetable mitogenic drivers.
Keywords : lung adenocarcinoma, gene sequencing, matched therapy, OncoKB