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BiomarkersLung Cancer

How Biomarkers Are Changing Lung Cancer Care

November 2022 – Lung Cancer
Wayne Kuznar

Smoking remains the main cause of lung cancer, responsible for about 84% of lung cancers in American women and 90% of lung cancer in American men who smoke or have smoked in the past, but that leaves about 10% to 15% of patients who have never smoked and yet are diagnosed with lung cancer.1

In addition to smoking, and other environmental causes of lung cancer, researchers have discovered many biological markers, or biomarkers that are driving cancer and its progression, especially non–small-cell lung cancer (NSCLC). These biomarkers represent molecular changes in our DNA that can promote cancer cells, which explains why even seemingly healthy people who have never smoked are diagnosed with lung cancer.

In response to this understanding, lung cancer treatment is now increasingly being driven by these biomarkers. Most of the known biomarkers in lung cancer have been identified in patients with NSCLC, and therefore, the current treatments for these biomarkers target patients with NSCLC and not those with small-cell lung cancer.

Nevertheless, some cancer guidelines now call for all patients with lung cancer to be tested for biomarkers, because new biomarkers are being discovered in patients with NSCLC as well as in those with small-cell lung cancer.

Lung Cancer Biomarkers

Managing lung cancer by targeting specific biomarkers with targeted therapies has fundamentally changed the way many cancers, including lung cancer, are being treated today, said Josina Reddy, MD, PhD, Vice President of Product Development at Genentech, during a February 2022 virtual roundtable discussion about the role of biomarkers in cancer care.

“In this era of personalized cancer care, identifying those biomarkers in a patient’s tumor tissue or using blood is an essential step in developing a personalized treatment plan,” Dr. Reddy said.

“For a growing share of patients, that treatment plan might include targeted therapies. For some patients, it might involve immunotherapies that help to engage the body’s own immune system to fight the cancer,” Dr. Reddy added.

Genomic Mutations

The most common biomarkers in lung cancer for which targeted therapies are now available include genetic or genomic mutations such as EGFR, ALK, BRAF, HER2, KRAS, MET, RET, and ROS1.

PD-1/PD-L1 Biomarker

Suzanne Topalian, MD

Another type of biomarker in lung cancer is expression of the PD-1/PD-L1 protein that is found on some cancer cells, and is responsible for the cancer progression. Unlike the genomic mutations, this type of biomarker is more likely to respond to immunotherapy instead of targeted therapies. Therefore, current immunotherapies known as PD-1/PD-L1 inhibitors, or immune checkpoint inhibitors, have been approved for patients with lung cancer that is involved with this biomarker.

“PD-L1 is a marker that can change over time, and it’s a marker that can have different levels of expression in different sites of metastatic disease in an individual patient,” said Suzanne Topalian, MD, Professor of Surgery and Oncology at Johns Hopkins Medicine in Baltimore, Maryland.

Comprehensive Biomarker Testing

With the solid understanding of the role of biomarkers in lung cancer, patients with lung cancer today can only be matched with the best treatment if they have a correct diagnosis, “and that means getting tested for all relevant biomarkers at the start of their journey,” said Dr. Reddy.

But not all patients with cancer are being tested for biomarkers today, and many don’t undergo comprehensive testing for all the potentially relevant biomarkers, using next-generation sequencing. To select the right therapy among the more than 20 or 30 targeted therapies approved for patients with NSCLC requires comprehensive biomarker testing.

Some of the available drugs are suitable for only a small number of patients, perhaps 1% or 2%, “but if you or your loved one is one of the 1% or 2%, these targeted treatment options will make a difference,” Dr. Reddy said. “Taken together, these seemingly small percentages of patients add up to a substantial percentage of patients with cancer who could benefit.”

If you’re a patient, ask for comprehensive biomarker testing as soon as possible, before starting therapy.

Multiple Biomarkers

The future of lung cancer treatment points to the use of multiple biomarkers for many tumor types, which may require the use of a combination of several targeted therapies or immunotherapies.

In fact, several combinations of immunotherapies are now used for patients with PD-1/PD-L1, such as a combination of a PD-1 inhibitor plus a CTLA-4 inhibitor, which targets the BRAF mutation in lung cancer.

George Demetri, MD

George Demetri, MD, Director of the Sarcoma Center, Dana-Farber Cancer Institute in Boston, focused on NSCLC as an example of cancer with many biomarkers that affect the treatment plan for individual patients, and the continuing search for new biomarkers.

“I think we’ll find more reliable biomarkers, and it’s probably going to have to be multiple biomarkers, pointing to combinations [of therapies] almost certainly,” said Dr. Demetri.

In some patients whose tumors don’t have a biomarker, their cancer may still respond to a particular targeted drug, because our understanding of biomarkers is not complete.

According to Dr. Topalian, the hope is that using combinations of biomarkers will be much more sensitive and precise than the ones currently in use. “I’m excited about the potential for multidimensional or multiplex biomarkers,” she said.

Ask Your Oncologist

Every patient with NSCLC should have a complete biomarker testing using molecular profiling and next-generation sequencing. Patients should also have their PD-1/PD-L1 levels tested, to see if they may benefit from targeted therapies or immunotherapy.

If your doctor does not order biomarker testing for you after your diagnosis, be sure to ask why. Testing should be done before starting treatment, to ensure you get the best therapy available for you.

Biomarker testing may not be right for every person, especially for smokers or those with a history of smoking, but most patients with lung cancer should ask about comprehensive biomarker testing and PD-1/PD-L1 testing before starting therapy.

Reference

  1. American Cancer Society. Most people with lung cancer smoked. www.cancer.org/research/acs-research-highlights/lung-cancer-research-highlights/most-people-with-lung-cancer-smoked.html.

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Last modified: November 16, 2022

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