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Expert Breaks Down Testing for Genetic Alterations in Metastatic Lung Cancer

With new therapies that can target specific genetic mutations in patients with lung cancer, testing the tumor’s makeup is becoming increasingly important, according to Joshua Bauml, M.D.
 
BY Brielle Urciuoli
PUBLISHED September 21, 2018
With new therapies that can target specific genetic mutations in patients with lung cancer, testing the tumor’s makeup is becoming increasingly important, according to Joshua Bauml, M.D.

The Food and Drug Administration (FDA) has approved targeted therapies to treat patients with four gene mutations – EGFR, ALK, ROS1 and BRAF – in the lung cancer space.

“The therapies are very effective when we use them in a targeted way,” said Bauml, who is an assistant professor of medicine at the Hospital of the University of Pennsylvania, at the 10th Focus on Lung Cancer Conference. “The response rate by which patients gain benefit for these drugs is much better. The quality of life is much better. They’re taking a pill once or twice a day instead of coming in for infusions.”

However, in order to receive these gene-specific targeted therapies, patients must first have their lung cancer tested to see which, if any, genetic mutations they harbor.

Bauml said that tissue biopsies – where a small sample of the tumor is extracted – were the “gold standard” of genetic testing in lung cancer. However, this method comes with some downfalls. At diagnosis, tumors that have targetable genetic mutations are usually uniform in the makeup of their cells. However, if that tumor develops a resistance to therapy, it can come from only a small group of cells that become different from the rest of the tumor.

Not to mention, tissue biopsies can only test for one genetic mutation at a time, potentially leading to multiple invasive tests for the patient.

“Doing these repeat biopsies is not easy for the patient,” Bauml said. “The problem is that each of these tests can only look at one thing at a time. And when you do biopsies, you can only get a small amount of tissue. This led to the development of next-generation sequencing. It takes that same little bit of tissue, and instead of testing for one gene, it tests for hundreds or even thousands on one little piece of tissue.”

Bauml mentioned that every patient with metastatic adenocarcinoma of the lung should receive next-generation sequencing – even if they are current or former smokers.

“One of the biases is that people with a history of smoking shouldn’t be tested,” Bauml said, explaining that while genetic alterations are most common in never or light smokers, they can also be seen in people with a tobacco history. So, those who smoked should not have their disease written off as something that came only from the habit, Bauml said.

While all patients with metastatic disease might want to talk to their health care team about next-generation sequencing, experts in the field are still undecided about whether or not those with early-stage lung cancer should be tested.

“Testing earlier than at the metastatic stage is controversial because right now we don’t change our treatment before metastatic disease because, right now, these are not curative treatments,” Bauml said.

Even in patients who are tested, less than half will end up having a targetable genetic mutation – which can be isolating for the minority in this population. Bauml emphasized that there are many online and in-person support groups for patients to join and connect with others with a similar diagnosis.

“Having one of these rare genetic mutations can be very isolating,” he said. “But you’re really not alone in the modern era of social media.”

 
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