Genetic alterations in lung cancers help select treatment

The introduction of targeted therapy has transformed the care of patients with lung cancers by incorporating tumor genotyping into treatment decisions. Adenocarcinoma, the most common type of lung cancer, is diagnosed in 130,000 patients in the United States and 1 million persons worldwide each year. Adenocarcinoma is also the type of lung cancer with a higher than 50 percent estimated frequency of actionable oncogenic drivers, which are molecular abnormalities that are critical to cancer development. These drivers are defined as "actionable" because the effects of those abnormalities can be negated by agents directed against each genomic alteration, according to background information in the article.

Mark G. Kris, M.D., of Memorial Sloan Kettering Cancer Center, New York, and colleagues examined the frequency of oncogenic drivers in patients with lung adenocarcinomas, and the proportion of patients in whom this data was used to select treatments targeting the identified driver(s) along with overall survival. From 2009 through 2012, 14 sites of the Lung Cancer Mutation Consortium enrolled patients with metastatic lung adenocarcinomas and tested the tumors of patients who met certain criteria for 10 oncogenic drivers.

During the study period, tumors from 1,007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64 percent). Results were used to select a targeted therapy or clinical trial in 275 of 1,007 patients (28 percent).

The 260 patients with an oncogenic driver and treatment with a targeted agent had a median (midpoint) survival of 3.5 years; the 318 patients with a driver and no targeted therapy, 2.4 years; and the 360 patients with no driver identified, 2.1 years.

The authors conclude that multiplexed tested aided physicians in selecting lung cancer therapies. Although individuals with drivers receiving a matched targeted agent lived longer, the study design was not appropriate to reach definitive conclusions about survival differences being attributable to the use of oncogenic drivers.

Editorial: Non-Small Cell Lung Cancer and Precision Medicine

Boris Pasche, M.D., Ph.D., of Wake Forest University, Winston-Salem, N.C., and Stefan C. Grant, M.D., J.D., M.B.A., of the University of Alabama at Birmingham, comment on the findings of this study in an accompanying editorial.

"In summary, the study by Kris et al demonstrates the proof of principle that multiplex testing of actionable driver mutations is feasible and can allow for effective treatment stratification. After decades of small, albeit significant, improvements in the care of patients with lung cancer, the advent of genetic testing of tumors, identification of driver mutations, and development of drugs able to specifically target these mutations, have produced substantial improvements in survival for patients with targetable driver mutations. Although much remains to be done, the incorporation of genomic medicine into the study and treatment of lung cancer represents, at the very least, the end of the beginning for the care of these and other patients with cancer."