Genetic alterations in lung cancer help select treatment and may improve survival

Genetic alterations of lung cancer tumors were identified through multiplexed testing, and these alterations were helpful in selecting targeted treatments. Patients that received matched therapy for lung cancer lived longer than patients who did not receive directed therapy, although randomized clinical trials are required to determine if this treatment strategy improves survival, according to a new study.

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% 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, MD, of Memorial Sloan Kettering Cancer Center, New York, 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. The study was published in JAMA (2014; doi:10.1001/jama.2014.3741).

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%). Results were used to select a targeted therapy or clinical trial in 275 of 1,007 patients (28%).

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 concluded that multiplexed testing aided physicians in selecting lung cancer therapies. Although patients 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.

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