Oncogenic drivers effective at guiding lung adenocarcinoma therapy

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1. Oncogenic drivers were identified in 64% of lung adenocarcinomas. 

2. Median survival was longer in patients treated with therapies targeted at the oncogenic drivers. 

Evidence Rating Level: 2 (Good) 

Study Rundown: Lung adenocarcinoma is the most common type of lung cancer diagnosed in the United States. Over half of these malignancies have identifiable mutations that are critical to the development of tumors, called actionable oncogenic drivers. The Lung Cancer Mutation Consortium (LCMC) has identified these drivers as actionable because targeted therapy against them has been shown to negate or protract the neoplastic process. The LCMC designed this study to determine the frequency of oncogenic drivers, deduce the practicality of routine analysis, and evidence the effectiveness of using genetic findings to guide treatment. It was found that 64% of lung adenocarcinomas had at least one actionable driver mutation and that therapy guided by these findings led to increased medical survival from time of diagnosis. Interestingly only 3% of tumors demonstrated more than one actionable oncogenic driver.

This study’s main limitation is that it is not a randomized trial. The two cohorts of patients receiving targeted therapy did not have equivalent risk factors. Patients receiving targeted therapy were younger and more likely to not have been smokers, among other disparities. Additionally, almost a quarter of participants were ineligible for targeted treatment as a result of inadequate availability of biopsy tissue. Nevertheless, despite these limitations, this study supports findings demonstrated by prior research regarding the promising role of targeted therapy in future cancer treatments.

Click to read the study, published today in JAMA

Relevant Reading: A Genomics-Based Classification of Human Lung Tumors

In-Depth [prospective cohort]: This study was conducted by the LCMC and began in 2009 with a median follow-up time of 2 years. 34% of patients had never smoked and 64% had Stage IV cancer. A total of 623 of the 1007 enrolled patients that had studies to identify at least one oncogenic driver were positive. 733 enrolled patients had the full assay conducted to detect up to 10 drivers and revealed a driver in 64% of patients. Patients received therapy based on their oncologist’s recommendation and review by the LCMC. A total of 28% patients received targeted therapy and had a median survival range of 3.5 years (IQR 1.96-7.70). Patients with an oncogenic driver who had not received targeted therapy had a median survival range of 2.4 years (IQR, 0.88-6.20). KRAS, EGFR, and ALK were the most common drivers with occurrences of 25%, 17%, and 8% in this sample respectively.

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