Molecular Profiling for Lung Cancer Patients: Who Should Get Tested and What is it Like?

This means that many lung cancer patients won’t have to deal with the harmful effects of chemotherapy, like side effects and toxicity, because they’ll receive treatments that are finely tuned to their individual needs.

“I could not be more excited about targeted therapy. We’re discovering more and more targets and more known targets are becoming actionable,” Dr. Jared Weiss, a medical oncologist specializing in lung and head and neck cancer at UNC Lineberger Comprehensive Cancer Center, tells SurvivorNet.

Molecular Profiling for Lung Cancer Patients: Who Should Get Tested?

“It’s absolutely clear that every stage four patient with non-squamous, non-small cell lung cancer should have comprehensive and sensitive molecular testing done early, and with  PD-L1,” Dr Weiss explains.

PD-L1 refers to an expression of a protein on cancer’s surface that it may be using to avoid detection by the immune system.

NGS has become the standard of care in lung cancer treatment. You may be a candidate for NGS testing if you have been diagnosed with:

• Advanced stage adenocarcinoma of the lung
• Advanced stage squamous cell cancer of the lung
• Advanced stage adenosquamous cancer of the lung

In early stage lung cancer, you should discuss if NGS testing could be right for you, too.

PD-L1 testing and Immune checkpoint inhibitors

“It’s standard of care to get some kind of PD-L1 testing,” says Dr Weiss. PD-L1 testing is different from NGS Testing. It measures the level of certain proteins in cancer cells.

PD-1, also known as programmed cell death 1, is a protein that is found on the outer surface of cells in your immune system.

“PD-L1 is not a mutation. It is an expression of a protein on the cancer surface, that it might be using to hide from the immune system,” Dr. Weiss explains.

If you were recently diagnosed with lung cancer, your oncologist should discuss PD-L1 testing with you. This laboratory test helps physicians determine whether a patient will likely benefit from immunotherapy, since a third of patients with late-stage NSCLC have high levels of PD-L1.

Immune checkpoint inhibitors are a type of immunotherapy that has been recently used as a first-line treatment for lung cancer patients with metastatic disease. They are man-made antibodies that shut down key proteins on immune cells that, when turned on, can give cancer a free pass to spread.

Most Common Mutations in Lung Cancer

“Parallel to the PD-L1, is the molecular testing, which is asking about the mutations in lung cancer,” says Dr Weiss.

Lung cancers often carry mutations within their genes. Commonly seen mutations include TP53, KRAS, EGFR, and ALK, which are found in 50%, 30%, 10-15%, and 5% of Non-Small Cell Lung Cancer (NSCLC) respectively.

While these mutations contribute to the onset and spread of NSCLC, at least a few of these also make it a good target for highly-specific and effective drugs. For example, cancers with the EGFR mutation can be targeted by EGFR inhibitors, which can lead to good patient outcomes. The KRAS gene mutation itself is also targetable by specific medications.

For people with lung cancer, the goal of NGS is to find your tumor’s specific mutations; and then target those mutations with an already-approved therapy or a targeted therapy. NGS testing gives your doctor a more complete profile of your lung cancer to help identify proven, targeted treatments.

The following are the most common mutations that have FDA-approved targeted treatment options already?

• EGFR
• ALK
• ROS1
• BRAF
• KRAS
• MET
• HER2
• RET
• NTRK

Lung Cancer Targeted Agents Made Possible Using NGS Testing

• EGFR Mutations: These are present in about 10-15% of lung cancers in the United States. Tagrisso (generic name: osimertinib), is an oral medication approved for EGFR gene mutation.
• Targeting EGFR exon20 mutation was a challenge for a long time and yet this is one of the most common mutations we find when we do NGS testing. Exkivity (Generic name: mobocertinib) and Rybrevant (generic name: amivantamab) are the two drugs that target EGFR exon20 mutations.
• KRAS mutations occur in about 20% of patients with lung adenocarcinomas. Lumakras (generic name: Sotorasib) and Krazati (generic name: Adagrasib) can target KRAS G12C mutations.
• Targeted therapy may still be an option even if your cancer grows after being on first-line therapy.
• If you do not test positive for any of the mutations with an approved targeted therapy, you may qualify for immunotherapy with or without traditional chemotherapy based on your PD-L1 testing.

How is Molecular Profiling performed?

Dr. Weiss explained to SurvivorNet, in a very clear way, how this could all play out:

“If I meet a patient for the first time and they haven’t yet had this testing [which I think is the case in most places in the country, where the medical oncologist meets the patient and nothing’s been ordered], I’d have the conversation in the plainest english that I can muster, about why it matters.”

“And then I will talk to the pathologist and see if we have tissue left [from a previous biopsy or surgery], because nobody wants another needle stuck into them. If there’s adequate tissue remaining, it’s just an order, right?  I sign an order, the tissue goes off, and we test the tissue for these changes.”

In addition, Dr. Weiss says, he tests PD-L1 and performs what is called “liquid biopsy,” which is a blood test that looks for dead cancer cells circulating in your bloodstream. This is a newer technology but is also very important to do in tandem, according to Dr Weiss.

“One, it’s another shot on goal for getting an answer, right? If the tissue is inadequate, if there isn’t enough left, if there’s some quality problem with it, this is a second way to get at it. And number two, it’s faster. The good testing (NGS tumor-based testing) can take three or four weeks.  And no one wants to wait three or four weeks. If the blood gets you an answer, it can get you an answer within days to a week.”

Types of NGS Testing On The Market

There are a number of tests you may encounter, depending on where you are getting treatment and what you are getting treatment for. Here are some of the common ones currently on the market:

• FoundationOne®CDx looks at 324 genes in solid tumors and says it can takes up to 12 days for results. Test results include microsatellite instability (MSI) and tumor mutational burden (TMB) to help inform immunotherapy decisions.
• OmniSeq Insight provides comprehensive genomic and immune profiling for all solid tumors. It looks for 523 different genes. Test results include microsatellite instability (MSI) and tumor mutational burden (TMB), as well as PD-L1 by immunohistochemistry (IHC).
• Cobas EGFR Mutation Test v2 identifies 42 mutations in exons 18, 19, 20 and 21 of the epidermal growth factor receptor (EGFR) gene. It is designed to test both tissue and plasma specimens with a single kit, and allows labs to run tissue and plasma on the same plate simultaneously.

You should ask your healthcare team if the brand of molecular testing they are doing is optimal for your cancer type.

Lung Cancer Overview

Lung cancer is the second most common form of cancer, and the leading cause of cancer deaths in both men and women in the United States. It can be particularly tricky to treat because often, symptoms don’t show up until the cancer has spread to other organs.

There are two main types of lung cancer, which doctors group together based on how they act and how they’re treated:

• Non-small cell lung cancer (NSCLC) is the most common type and makes up about 85% of cases
• Small cell lung cancer (SCLC) is less common, but it tends to grow faster than NSCLC and is treated very differently

Questions to Ask Your Doctor

• What type of lung cancer do I have?
• Should I have comprehensive and sensitive molecular testing?
• What mutations does my tumor have?
• Am I eligible for immunotherapy?
• Are there experimental studies that I’m a potential candidate for? Should I consider one of these studies?

Learn more about SurvivorNet's rigorous medical review process.

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