What You Need to Know About Biomarker Testing for Lung Cancer

The term “precision medicine” has been a buzzword in cancer treatment for many years now. But its notoriety comes with good reason — it has revolutionized treatment and improved survival for countless cancer patients.

In particular, precision medicine, also called personalized medicine, has made a significant impact on patients with non-small cell lung cancer (NSCLC). Over the last 15 years, advances in biomarker testing have allowed doctors and scientists to develop more targeted and effective treatment options for NSCLC.

This form of precision medicine continues to show promise for future lung cancer therapies — providing hope that lung cancer patients can live longer, better quality lives.

“We’re making major progress in our fight against lung cancer,” says Suresh S. Ramalingam, MD, FACP, FASCO, nationally noted lung cancer treatment expert and executive director of Winship Cancer Institute of Emory University. “Now it is possible to personalize therapy to a patient sitting in front of us by conducting biomarker testing. We’ve always known that every patient has their own different clinical behavior of their cancer journey.”

What is Biomarker Testing?

Everyone’s cancer has a unique set of biomarkers. Biomarker testing looks for proteins, genes or molecules that can provide information about your unique cancer case and can help doctors determine whether it will respond to a certain treatment.

Biomarker testing is also sometimes called tumor testing, genomic testing or molecular testing. It’s different from genetic testing, which looks for inherited gene mutations that make it more likely for someone to get cancer. Inherited gene mutations are something you’re born with; biomarker testing looks for gene mutations that develop throughout your life.

“We now have a better understanding of some of the biological features that drive lung cancer’s varying behavior,” says Dr. Ramalingam, “so we now recommend that every patient diagnosed with non-small cell lung cancer, which is the most common form of lung cancer, to undergo biomarker testing.”

Lung Cancer Biomarker Testing

Doctors typically do biomarker testing on patients with a subtype of NSCLC called adenocarcinoma. Patients with squamous cell lung cancer or small cell lung cancer are less likely to have biomarkers. Still, doctors may decide to do testing if the patient was never a smoker.

During a comprehensive biomarker test, doctors will look for changes in certain genes tied to lung cancer, including:

• ALK
• BRAF
• EGFR
• KRAS
• MET
• NTRK
• RET
• ROS1
• V600E

In most cases, a biomarker test will also check for signs of the PD-L1 protein. Tumors that have certain levels of PD-L1 may be more susceptible to immunotherapy treatments, which use the body’s immune system to fight cancer.

What Role Does Biomarker Testing Play in Lung Cancer Treatment?

Biomarkers can tell doctors whether your cancer will respond to certain treatments. With this information, your doctor can find targeted therapies or immunotherapies that may more effectively destroy cancer cells. These targeted treatments may also lead to fewer side effects.

Patients who undergo biomarker testing can also join research studies to test new targeted therapies. Some clinical trials enroll patients based on specific biomarkers rather than the type of cancer they have.

Biomarker-Based Targeted Therapies for Lung Cancer

Biomarker testing and targeted therapy is not a new concept for lung cancer treatment. Still, it continues to show promise. The first personalized therapy treatments for lung cancer targeted the EGFR gene, which was detected in 2004. Since then, doctors and researchers have developed five treatments that target the EFGR mutation.

One of those EGFR-targeted treatments is osimertinib, which was tested in the FLAURA study on patients with advanced NSCLC. The results, released in 2018, showed that the median overall survival rate for patients on osimertinib was 38.6 months, compared to 31.8 months for the standard treatment. The three-year survival rate for patients taking osimertinib was 54%, compared to 44% on the standard therapy.

First-line targeted treatments have also been approved for NSCLC patients with EGFR, ALK, ROS1, BRAF and NTRK biomarkers.

And work is still ongoing to develop even more biomarker-based targeted treatments. More recently, researchers have seen promising results in therapies targeting the KRAS gene and HER2 gene.

Combining biomarker testing with immunotherapy

With biomarker testing also checking for the PD-L1 protein, doctors have been able to identify lung cancer patients who may respond better to immunotherapy treatment. Approximately 30% of patients with metastatic NSCLC have high levels of PD-L1.

There are currently five immune checkpoint inhibitors approved for lung cancer. Immune checkpoint inhibitors are a type of immunotherapy that allows the immune system to attack and kill cancer cells. These treatments have shown significant promise in treating NSCLC — one type of immune checkpoint inhibitor, pembrolizumab, had a five-year survival rate of 32%.

Looking Ahead at the Future of Biomarker Testing

Although biomarker testing shows incredible promise in lung cancer treatment, testing is still not done as often as it should be. According to a survey from the International Association for the Study of Lung Cancer, 61% of respondents said their patients don’t undergo biomarker testing. Barriers to testing include time, access, quality, cost and awareness of the tests themselves.

More research is also needed to study the relationship between biomarker testing, targeted therapies and circulating tumor DNA (ctDNA). The ctDNA breaks off from dying tumor cells and releases into the bloodstream.

Early data shows that ctDNA may help find which cancers will resist targeted therapy. In the 2018 data from the FLAURA trial, ctDNA helped identify treatment-resistant cancer in 66% of patients before those patients’ disease progressed.

Thanks to biomarker testing and targeted therapies, lung cancer treatment has improved significantly in the last decade. But with more research into ctDNA and better awareness about the power of biomarker testing, there’s more hope than ever before.

“By doing biomarker testing,” says Dr. Ramalingam, “we can come up with either targeted therapies, immunotherapy, or a combination approach that has the best potential to achieve long-term survival for that given patient.”

About Winship Cancer Institute of Emory University