Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: The NCI’s Lung Cancer Mutation Consortium (LCMC).

Lung Cancer - Metastatic/Non-small Cell
Session Type and Session Title: 
Oral Abstract Session, Lung Cancer - Metastatic/Non-small Cell
Abstract Number: 


J Clin Oncol 29: 2011 (suppl; abstr CRA7506)
M. G. Kris, B. E. Johnson, D. J. Kwiatkowski, A. J. Iafrate, I. I. Wistuba, S. L. Aronson, J. A. Engelman, Y. Shyr, F. R. Khuri, C. M. Rudin, E. B. Garon, W. Pao, J. H. Schiller, E. B. Haura, K. Shirai, G. Giaccone, L. D. Berry, K. Kugler, J. D. Minna, P. A. Bunn; Memorial Sloan-Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; Massachusetts General Hospital, Boston, MA; University of Texas M. D. Anderson Cancer Center, Houston, TX; Partners Health Cancer Center, Boston, MA; Massachusetts General Hospital Cancer Center, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Winship Cancer Institute of Emory University, Atlanta, GA; The Johns Hopkins University, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA; University of Texas Southwestern Medical Center, Dallas, TX; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Medical University of South Carolina, Charleston, SC; National Cancer Institute, Bethesda, MD; Vanderbilt University, Nashville, TN; University of Colorado Cancer Center Denver, Aurora, CO; University of Colorado Denver Cancer Center, Aurora, CO

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: The ability to detect driver mutations like EGFR and EML4-ALK in tumor specimens from patients with lung cancer and administer agents targeting those molecular lesions has revolutionized the management of adenocarcinoma of the lung. The availability of multiplexed assays to detect mutations permits the identification of multiple driver mutations from tumors at diagnosis. The number of molecular lesions and new agents to target them continues to grow. To exploit this, we created the LCMC to determine 10 driver mutations in tumors from 1,000 patients and to give the results to clinicians for care and entry onto targeted therapeutic trials based on these findings. Methods: The 14 member LCMC is prospectively enrolling patients to test tumors from patients with lung adenocarcinoma in CLIA laboratories for KRAS, EGFR, HER2, BRAF, PIK3CA, AKT1, MEK1, and NRAS using standard multiplexed assays and fluorescence in situ hybridization (FISH) for ALK rearrangements and MET amplifications. All are stage IIIB/IV, PS 0-2, have available tissue, and signed consent. Results: 830 patients have been registered with 50 enrolling monthly. We detected a driver mutation in 60% (252/422, 95% CI 55 to 65%) of tumors thus far. Mutations found: KRAS 107 (25%, 95% CI 21 to 30%), EGFR 98 (23%, 95% CI 19 to 27%), ALK rearrangements 14 (6%, 95% CI 4 to11%), BRAF 12 (3%, 95% CI 1 to 5%), PIK3CA 11 (3%, 95% CI 1 to 5%), MET amplifications 4 (2%, 95% CI 0.5 to 5%), HER2 3, (1%, 95% CI 0.1 to 2%), MEK1 2 (0.4%, 95% CI 0.1 to 2%), NRAS 1 (0.2%, 95% CI 0.01 to 1%), AKT1 0 (0%, 95% CI 0 to 1%). 95% of molecular lesions were mutually exclusive. Conclusions: We detected an actionable driver mutation in 60% of tumors from prospectively studied patients with lung adenocarcinoma. Results of EGFR mutation testing are given to treating physicians to select erlotinib as initial treatment per NCCN and ASCO guidelines. Patients with other driver mutations are offered participation in LCMC-linked trials of agents targeting the mutation identified, e.g. crizotinib with EML4-ALK. At half of LCMC sites, multiplexed testing for all mutations is now routine practice in their pathology departments. Supported by 1RC2CA148394-01.