The identification of oncogenic drivers has helped transform the care of patients with adenocarcinoma, the most common type of lung cancer diagnosed in 130,000 patients in the United States and 1 million persons worldwide annually. Adenocarcinoma has a >50% estimated frequency of actionable oncogenic drivers, which are genetic alterations that are critical to the development and maintenance of cancer. In a new study, researchers sought to determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select targeted therapy and to measure survival (Kris MG, et al. JAMA. 2014;311:1998-2006).
From 2009 through 2012, 14 sites of the Lung Cancer Mutation Consortium enrolled patients with stage IV or recurrent adenocarcinoma of the lung and tested tumors of patients who met certain criteria for 10 oncogenic drivers. Most of the patients were former smokers, and 34% never smoked. In all, 64% of patients had stage IV disease at diagnosis.
Among the 1017 patients with confirmed adenocarcinoma, tumors from 1007 patients were tested for at least 1 gene; 733 patients had tumors fully genotyped and were tested for 10 genes. Of the 733 patients, an oncogenic driver was found in 466 (64%) patients. Among these 733 tumors, KRAS mutations were the most frequent (25%), followed by the sensitizing epidermal growth factor receptor (17%) and anaplastic lymphoma kinase rearrangements (8%).
The results were used to select a targeted therapy or clinical trial in 275 of 1007 (27%) patients. The 260 patients with an oncogenic driver and treatment with a targeted agent had a median survival of 3.5 years compared with 2.4 years in 318 patients with a driver and no targeted therapy, and 2.1 years in 360 patients with no identified driver.
Multiplexed testing of lung cancer tumors identified genetic alterations that were helpful in physicians selecting targeted treatment. Patients who received matched therapy for lung cancer lived longer than patients who did not receive directed therapy. Despite lengthened survival, the researchers noted that randomized clinical trials are needed to determine if selected targeted therapies based on oncogenic drivers improve survival.
