Evolving NSCLC Treatment Paradigm - Episode 1

Pathology of Stage IV Lung Adenocarcinoma

Alexander Drilon, MD:Lung cancer can be broken down into non—small cell lung cancer and small cell lung cancer. Non–small cell lung cancers are the most common type of lung cancer and occur in about 4 out of 5 patients, and the most common histology for non–small cell lung cancers is adenocarcinoma. In general, in the United States, about 200,000 cases are diagnosed a year, and so it makes it a very substantial population of patients with this burden of disease.

Justin Gainor, MD:Over the past 15 years, we’ve come to recognize that advanced lung cancer can really be divided and stratified based on patients who have genetic alterations and oncogenic drivers. The first targetable oncogenic driver that was identified was the epidermal growth factor receptor, which was identified in 2004. We’ve since learned that these genetic alterations are found in about 10% to 15% of western patients, and these patients tend to have characteristic clinical and pathologic characteristics. Most notably, we know that these genetic alterations confer sensitivity to treatment with targeted therapies or tyrosine kinase inhibitors [TKIs].

Since the initial discovery ofEGFRmutations in lung cancer, we’ve come to recognize this as a paradigm of trying to identify oncogenic drivers that could be targeted with TKIs. Collectively, we know that in the United States, there are 4 different genetic alterations where we have FDA-approved targeted therapies. These areEGFR,ALK,ROS1, andBRAF. And, in general, patients with these specific genetic alterations tend to have pretty characteristic clinical and pathologic characteristics. For example, patients withEGFR,ALK, andROS1—these tend to occur in patients who have a never or a very light smoking history. The same can be said for emerging oncogenic drivers such asRETrearrangements, which, again, tend to be enriched for patients with a never or light smoking history. One of the outliers of this, though, isBRAF.BRAFmutations are found in 4% of patients with lung cancer. And in contradistinction to the other targetable alterations,BRAFmutations can also be seen in patients who have a heavy smoking history.

Transcript edited for clarity.