The Importance of Genetic Testing: New Research Finds That Some Lung Cancers in ‘Never-Smokers’ Have Gene Mutations That Can Be Treated With Already-Approved Drugs; See the List

The new analysis, which was published in the Journal of Clinical Oncology on Sept. 30, suggests that between 78% to 92% of lung adenocarcinoma (a type of non-small cell lung cancer) in patients who are “never-smokers” can be treated with precision drugs to target specific mutations in a patient’s tumor. (Lung adenocarcinoma, according to the National Center for Biotechnology Information, is the most common lung cancer seen in the U.S. It also has a strong association with previous smoking.)

“Most genomic studies of lung cancer have focused on patients with a history of tobacco smoking,” said senior author Dr. Ramaswamy Govindan, a professor of medicine at the school. “And even studies investigating the disease in patients who have never smoked have not looked for specific, actionable mutations in these tumors in a systematic way.”

“We found that the vast majority of these patients (“never-smokers”) have genetic alterations that physicians can treat today with drugs already approved for use,” he added. “The patient must have a high-quality biopsy to make sure there is enough genetic material to identify key mutations. But testing these patients is critical. There is a high chance such patients will have an actionable mutation that we can go after with specific therapies.”

“Our study highlights the need to obtain high-quality tumor biopsies for clinical genomic testing in these patients, so we can identify the best targeted therapies for their individual tumors.”

What is a Driver Mutation?

These are are specific mistakes in the DNA that fuel tumor growth. The mutations can be blocked with a variety of drugs, according to researchers. And what’s more interesting is researchers found that only about half of lung tumors in people who smoke have driver mutations.

There are various different driver mutations: KRAS, EGFR, ALK, ROS1, BRAF, RET, MET and NTRK. And each of these mutations can be treated with targeted drugs that are already approved by the FDA. Here is a list of drugs that are already approved to treat each driver mutation.

• KRAS is treated with sotorasib (brand name: Lumakras)
• EGFR is treated with erlotinib (Tarceva); afatinib (Gilotrif); gefitinib (Iressa); osimertinib (Tagrisso); or dacomitinib (Vizimpro)
• ALK is treated with crizotinib (Xalkori); ceritinib (Zykadia); alectinib (Alecensa); brigatinib (Alunbrig); or lorlatinib (Lorbrena)
• ROS1 is treated with crizotinib (Xalkori); ceritinib (Zykadia); lorlatinib (Lorbrena); or entrectinib (Rozlytrek)
• BRAF is treated with dabrafenib (Tafinlar) or trametinib (Mekinist) this drug is known as a MEK inhibitor, because it attacks the related MEK proteins.
• RET is treated with selpercatinib (Retevmo) or pralsetinib (Gavreto)
• MET is treated with sapmatinib (Tabrecta) or tepotinib (Tepmetko)
• NTRK is treated with larotrectinib (Vitrakvi) or entrectinib (Rozlytrek) a small number of non-small cell lung cancers have changes in one of the NTRK genes.

Lung Cancer: Smokers vs. Non-Smokers

The U.S. Centers for Disease Control and Prevention reports that in the United States, between 10% and 20% of lung cancers (20,000 to 40,000 lung cancers each year) happen in people who have never smoked, or smoked fewer than 100 cigarettes in their lifetime.

Lung Cancer in Smokers vs. Non-Smokers

For those who do smoke, however, it should be noted that the tobacco in cigarettes is a carcinogen that causes mutations in lung cells and enables the growth of cancer. Several thousand other lung cancer deaths are caused by exposure to secondhand smoke  — about 7,300 cases each year, according to the CDC.

But there is good news. According to SurvivorNet experts, if you quit smoking, your risk for lung cancer decreases.

“If you’re smoking, don’t smoke,” Dr. Joseph Friedberg, head of thoracic surgery at the University of Maryland School of Medicine, tells SurvivorNet. “You never return down all the way to the (level of) the person who never smoked as far as your risk of lung cancer goes, but it goes down with time.”

The Research

Researchers analyzed lung tumors from 160 patients with lung adenocarcinoma but no history of tobacco smoking. The never-smoker status of a patient was verified by examining the mutation patterns in these patients and comparing them to mutation patterns in lung cancers of patients who had smoked.

Take it From a Guy Who Looks at Diseased Lungs Every Day Stop Smoking

Scientists still don’t know what causes lung cancer in never-smokers, but one possibility is that their genes –” genes they’ve had since birth” contain factors making them more likely to develop a lung tumor. But the researchers found that only 7% of never-smokers had mutations present at birth that increase their risk of cancer.

“There appears to be something unique about lung cancer in people who have never smoked,” Govindan says. “We didn’t find a major role for inherited mutations, and we don’t see evidence of large numbers of mutations, which would suggest exposure to secondhand smoke.”

“About 60% of these tumors are found in females and 40% in males. Cancer in general is more common among men, but lung cancer in never-smokers, for some unexplained reasons, is more common among women. It is possible additional genes are involved with predispositions to cancers of this kind, and we just don’t know what those are yet.”

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