Incidence, characteristics, and survival of patients with EGFR-mutant lung cancers with EGFR T790M at diagnosis identified in the lung cancer mutation consortium (LCMC).

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
General Poster Session, Lung Cancer - Non-small Cell Metastatic
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 8085)
Mark G. Kris, Geoffrey R. Oxnard, Bruce E. Johnson, Lynne D Berry, Heidi Chen, David J. Kwiatkowski, Anthony John Iafrate, Ignacio Ivan Wistuba, Wilbur A. Franklin, Dara Aisner, Lecia V. Sequist, Fadlo Raja Khuri, Edward B. Garon, William Pao, Charles M. Rudin, Joan H. Schiller, Eric B. Haura, John D. Minna, Paul A. Bunn; Memorial Sloan-Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt University, Nashville, TN; Vanderbilt-Ingram Cancer Center, Nashville, TN; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA; The University of Texas MD Anderson Cancer Center, Houston, TX; University of Colorado Denver, Denver, CO; University of Colorado School of Medicine, Aurora, CO; Massachusetts General Hospital, Boston, MA; The Winship Cancer Institute of Emory University, Atlanta, GA; University of California, Los Angeles, Santa Monica, CA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; The University of Texas Southwestern Medical Center, Dallas, TX; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; University of Colorado Cancer Center, Aurora, CO

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Abstract Disclosures


Background: Somatic T790M mutations are detected in 62% of EGFR-mutant lung cancers with acquired resistance to EGFR TKIs, and have rarely been identified in the tumor at diagnosis and/or within the germline DNA. Multiplexed genotyping by the LCMC permitted us to evaluate the incidence of T790M at diagnosis, co-mutations, and survival of patients with this driver. Methods: The 14 member LCMC prospectively tested tumors of patients with lung adenocarcinomas in CLIA laboratories for mutations in EGFR and 9 other genes. We assayed T790Mby Sequenom, Snapshot, or Sanger sequencing. Germline DNA was not collected. Results: In the 987 tumors tested, 209 had mutations in EGFR alone: 25 T790M (2.5%) , 157 sensitizing EGFR mutations (exon 19 del, L858R, L861Q, G719X) without T790M, 23 exon 20 ins, 4 other mutations. 13 additional cases harbored mutations in EGFR and another driver; 2 with both T790M and PIK3CA. In each of the 27 EGFR-mutant cases with T790M, a coincident EGFR mutation was detected (18 exon 19 del, 9 L858R, 1 exon 20 ins). EGFR T790M was found more often than EGFR exon 20 ins or mutations in HER2 (1.9%), BRAF (1.6%), or PIK3CA (0.7%). Patients with T790M: 77% women, 81% never smokers, median age 55 (range 38-79), stage IV at diagnosis 81%, PS 0/1 100%. Characteristics did not differ from persons with sensitizing mutations and no T790M. Median survival from the diagnosis of metastatic disease for patients with EGFR-mutant lung cancers was 3.5 yrs with T790Mand 4.0 yrs without (p=0.926). Conclusions: T790M mutations were detected at diagnosis in 3% of adenocarcinomas and always coincident with another EGFR mutation. Cases with T790M represent 13% of all cases of EGFR- mutant lung cancer. Characteristics and survival for patients with EGFR- mutant lung cancers with T790M at diagnosis were similar to individuals with sensitizing mutations and no T790M. The observed incidence of T790M exceeded that of the other actionable targets HER2, BRAF, and PIK3CA. Trials should study this unique population identified by routine multiplexed genotyping. Supported by 1RC2CA148394-01 and the National Lung Cancer Partnership. Clinical trial information: NCT01014286.