Synapse - Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies

Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies Journal Article

Authors:	Jordan, E. J.; Kim, H. R.; Arcila, M. E.; Barron, D.; Chakravarty, D.; Gao, J. J.; Chang, M. T.; Ni, A.; Kundra, R.; Jonsson, P.; Jayakumaran, G.; Gao, S. P.; Johnsen, H. C.; Hanrahan, A. J.; Zehir, A.; Rekhtman, N.; Ginsberg, M. S.; Li, B. T.; Yu, H. A.; Paik, P. K.; Drilon, A.; Hellmann, M. D.; Reales, D. N.; Benayed, R.; Rusch, V. W.; Kris, M. G.; Chaft, J. E.; Baselga, J.; Taylor, B. S.; Schultz, N.; Rudin, C. M.; Hyman, D. M.; Berger, M. F.; Solit, D. B.; Ladanyi, M.; Riely, G. J.
Article Title:	Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies
Abstract:	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 preexistent 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. SIGNIFICANCE: An increasing number of therapies that target molecular alterations required for tumor maintenance and progression have demonstrated clinical activity in patients with lung adenocarcinoma. The data reported here suggest that broader, early testing for molecular alterations that have not yet been recognized as standard-of-care predictive biomarkers of drug response could accelerate the development of targeted agents for rare mutational events and could result in improved clinical outcomes. © 2017 AACR.
Journal Title:	Cancer Discovery
Volume:	7
Issue:	6
ISSN:	2159-8274
Publisher:	American Association for Cancer Research
Date Published:	2017-06-01
Start Page:	596
End Page:	609
Language:	English
DOI:	10.1158/2159-8290.cd-16-1337
PROVIDER:	scopus
PMCID:	PMC5482929
PUBMED:	28336552
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85020264202&doi=10.1158%2f2159-8290.CD-16-1337&partnerID=40&md5=9e1a032a4e0316eace0137bcc7e0b10a
Notes:	Article -- Export Date: 3 July 2017 -- Source: Scopus