ALK rearrangement has been found in 9.6% of lung cancer patients tested in the Lung Cancer Mutation Consortium, and MET amplification in another 4.1%, reflecting how many patients might benefit from targeted therapies such as crizotinib, according to research presented at the 14th World Conference on Lung Cancer in Amsterdam, hosted by the International Association for the Study of Lung Cancer (IASLC).
The Lung Cancer Mutation Consortium (LCMC), involving 14 U.S. cancer centers, was established to evaluate genetic alterations in 1,000 patients with advanced lung adenocarcinoma.
CLIA-certified labs at each site are using multiplex assays to profile eight genes previously linked to lung cancer, AKT1, BRAF, EGFR, HER2, KRAS, MEK1, NRAS and PIK3CA. Two other genes, ALK and MET, have been tested by fluorescence in situ hybridization (FISH) for rearrangements or amplifications.
"High quality molecular diagnosis for multiple markers can be achieved in a reasonable period of time to select patients for targeted therapy," said Prof. Marileila Varella Garcia, Ph.D., a professor of medical oncology at the University of Colorado School of Medicine.
Put simply, ALK rearrangement occurs when the head (promoter) and tail (active domain) of the gene split. Either part may then fuse with another gene. When the active domain of ALK fuses with a hyperactive promoter such as the EML4 promoter, it creates a fusion oncogene that has been associated with non-small cell lung cancer.
Lung cancer patients with ALK rearrangement have been found in previous studies to respond well to crizotinib, an ALK inhibitor.
In the LCMC study, researchers looked for ALK fusion with EML4 (EML4-ALK) or other partners, and MET amplification. ALK rearrangement was detected in 9.6% of patients and MET amplification in 4.1%.
ALK mutations were associated with younger age, median 52.3 years; ALK negative subjects had a median age of just under 60 years. ALK positive subjects were more likely to be never-smokers than ALK negative subjects (64% vs. 31%), less likely to have smoked in the past (33% vs. 61%) and more likely to have experienced liver metastasis (21% vs. 8%). No association was found between ALK-positive status and sex, gender, stage or brain metastasis.
Dr. Marileila Varella Garcia will discuss the research with journalists during a WCLC press conference at 10 a.m. CET on Tuesday, July 5. For individual interview requests, please call Renée McGaw at +31 20 549 3413 between July 3-7 in the press office at Amsterdam RAI, Amsterdam, the Netherlands. You may also email her at renee.mcgaw@ucdenver.edu
The LCMC is led by Dr. Paul A. Bunn, Jr., founder and former director of the University of Colorado Cancer Center and executive director of the IASLC.
About the IASLC:
The International Association for the Study of Lung Cancer (IASLC), based in Denver, Colorado, U.S.A., is the only global organization dedicated to the study of lung cancer. Founded in 1972, the association's membership includes more than 3,000 lung cancer specialists in 80 countries.
IASLC members promote the study of etiology, epidemiology, prevention, diagnosis, treatment and all other aspects of lung cancer and thoracic malignancies. IASLC disseminates information about lung cancer to scientists, members of the medical community and the public, and uses all available means to eliminate lung cancer as a health threat for the individual patients and throughout the world. Membership is open to any physician, health professional or scientist interested in lung cancer.
IASLC publishes the Journal of Thoracic Oncology, a valuable resource for medical specialists and scientists who focus on the detection, prevention, diagnosis and treatment of lung cancer. To learn more about IASLC please visit http://iaslc.org/