For years, researchers knew different factors were causing lung cancer tumors to grow, but they didn’t know why, or how to interrupt the process. Then, a group of lung cancer researchers discovered the EGFR biomarker, which opened the door for targeted therapies that were easier to take, more effective, and led to better patient outcomes than anything used before. Take this opportunity to hear from someone who had a part in discovering the first lung cancer biomarker. Learn more about the EGFR biomarker from Dr. Carbone – learn what every EGFR patient needs to know!

Guest

Dr. David Carbone is a lung cancer clinician, researcher and specialist at The Ohio State University Comprehensive Cancer Center. He’s been working on developing treatments for lung cancer for years, and played an important role in discovering the first targeted therapy aimed at the EGFR biomarker.

Transcript | Video Podcast

The Importance Of Access To Comprehensive Biomarker Testing

Biomarker testing is nothing short of a revolution in lung cancer treatments. Currently there are 10 – 12 different things that can be measured about a lung cancer tumor. These results can dramatically affect the type of treatment chosen for that patient. And historically people have said, “Well these two are more frequent than the others, so we’ll only measure these two. And if they’re negative, then we’ll measure another one.”

Dr. Cargone’s goal for optimal patient care is getting the right treatment to the right patient as rapidly as possible. Therefore, it’s very important to measure for an entire panel of these biomarkers all at the same time and before any treatment decision is made. It radically changes the best treatment options for that patient if one of these markers is identified.

What Every EGFR Patient Needs to Know – Get the Right Treatment Right From the Start

The right treatment for EGFR often is a targeted therapy. The way doctors refer to targeted therapies is a therapy that targets one of these specific EGFR alterations. So the EGFR gene is a gene that controls the growth of many cells in your body—and that’s how it was discovered.

And the cancers have found that if they can switch this gene on in an abnormal, unregulated way, that causes the cancer to grow in an abnormal unregulated way. In most tumors with this alteration, really the EGFR gene alteration is the primary driver of that cancer’s growth. This is why we call these alterations driver alterations or driver mutations.

Understanding EGFR Subtypes

The biomarker EGFR is a mutation in the DNA that turns on the gene called epidermal growth factor receptor. And it turns out that there’s many different ways the DNA can be altered in order to turn that gene on. It is important to know, not just that your tumor has an EGFR mutation, but precisely which alteration the tumor’s DNA has. The best treatment options for that patient should be tailored to these identified markers.

What targeted therapies are available to someone with EGFR and its various subtypes?

According to Dr. Carbone, the most current generation targeted therapy for the common EGFR mutations is osimertinib. And it’s been developed as a selective inhibitor of just the mutant form of this protein and not the normal form, since every cell in your body has the gene and many other cells, particularly skin and gut have actually expressed the protein as well.

This particular targeted therapy has a very good efficacy, a low toxicity, and is the most commonly prescribed first line treatment. It also has the advantage of having good brain penetration, and these types of tumors often spread to the brain and the osimertinib can prevent the development of brain metastases or even treat the ones that are found at diagnosis. Some of the other mutations are better targeted with other drugs.

“And so what we find is that, we can give these drugs, which are usually oral drugs, that they turn off this alteration specifically in the cancer cells. And sometimes almost like magic, the cancer melts away and the patients often have no side effects at all. It’s really a dramatic efficacy that we see when you have a known driver and you have a drug that targets that driver.”

Equity issues in biomarker testing awareness

Dr. Carbone points out that at his institution, there are 10 medical oncologists who do nothing but treat lung cancer patients. And they’re experts at all of these aspects. And I have full confidence that they do the right thing when it comes to biomarker testing. But in the community, you have a solo practitioner who treats every kind of cancer – breast cancer, colon cancer, sometimes even leukemias and lymphomas. They have to keep up to date in all those different cancer types. It’s extremely hard and very daunting to know all the details that are now important for treating a lung cancer patient.

If a lung cancer patient is not confident that the right thing is being done, getting a second opinion is a good choice. Because, as Dr. Carbone points out, “it is really important to get the right treatment first.”

What can a liquid biopsy tell you about a patient’s lung cancer?

EGFR is an example of a biomarker that’s tested in the DNA of the tumor. And historically you’ve needed a sample of the tumor in order to test for that biomarker in the tumor DNA. But now this blood biopsy technology has really developed to a pretty advanced state. Now these biomarkers, which are mutations or alterations in the DNA and the tumor, can actually be measured at tiny amounts in the peripheral blood.

A Negative Result Shouldn’t Stop Biomarker Testing

Although getting a positive from a blood sample is sufficient to act upon, blood biopsies are not quite as sensitive as a tissue analysis. There are a significant number of patients whose tumors truly have this EGFR biomarker that the blood analysis does not pick up. So in general, Dr. Carbone doesn’t rely only on a negative blood biopsy. He will look with a tissue biopsy. Because it makes such a huge difference to the way you manage patients.

“It really is tragic to miss this finding in even one patient and choose the wrong treatment for them. you’re really doing them a disservice. So we try to look very hard for these markers.”

So is immunotherapy effective for someone with the EGFR mutation?

In general, not. However, there are situations where doctors use immunotherapy with virtually every type of lung cancer. But it is the wrong treatment as a first treatment for EGFR mutated lung cancer. The response rate is extremely low for immunotherapy and very high for targeted therapy. And with the modern targeted therapy drugs, it’s definitely the wrong thing to start with. Now, there are regimens that include immunotherapy and after the tumor becomes resistant to targeted therapies. But it’s definitely the wrong thing to do to start with immunotherapy if you have a EGFR mutated tumor.

Side Effects of Targeted Therapy

Similarly, many people take chemotherapy with very tolerable, minimal side effects as well. But, Dr. Carbone says it’s safe to say that most people who take targeted therapy for EGFR mutated lung cancer have very few side effects that are very tolerable. And it’s primarily a mild skin rash, though, many people have none. Or slightly looser bowels than normal, that is readily controlled.

And the thing with side effects is it’s dependent on the type of treatment. So the side effects for immunotherapy are really totally different from the side effects for chemo, totally different from the side effects of targeted therapies and even different targeted therapies have different side effects. So, every time a patient starts on these, the doctor and the nurse should really explain to them what they might expect and how to deal with it.

With the modern drugs for EGFR targeted therapies, we get response rates that are super high. And 80, 90% of patients have substantial benefit from these drugs, but not everyone. And these drugs are generally not curative. So that when you treat a patient with EGFR mutant lung cancer with osimertinib, they can have a dramatic response that can last years. But in general, I tell patients, if you live long enough, the cancer will become resistant to this drug and we’ll have to look for a plan B.

EGFR Treatments Over The Years

Cancer treatment has advanced dramatically in the 35 years since Dr. Carbone has been treating lung cancer patients. Even though the treatments for lung cancer we have are good, they’re far from perfect.

We now often treat patients “beyond progression.” This journey being a patient will be on the drug, they’ll have 20 sites of disease, all of them will shrink nicely. But then one will grow. And now we can use targeted radiation, for example, or even surgery to treat that one escaping tumor. And then continue the drug. And sometimes for years beyond that targeted therapies are able to control the general disease. So we’ve learned not only to switch to different therapies, but how to better manage a patient on their first line therapy.

Dr. Carbone thinks that there’s some very exciting research that’s going on now, for example, to make the depth and duration of the efficacy of these targeted agents better from the very beginning of treatment.

Clinical Trials: Tomorrow’s Drugs Available Today

And so we have a trial that we now have are treating patients on. Combining osimertinib with a drug that targets beta-catenin, which is a resistance pathway. And so, I think that’s a worthwhile trial to be enrolled in.

But also when the tumor becomes resistant, there are trials trying different drug combinations and alternative drugs to treat patients whose tumors have become resistant to first line therapy. So, I tell patients that clinical trials are tomorrow’s drugs available today. Tomorrow’s standard of care available now is part of a clinical trial. And with these imperfect treatments, I think it’s very reasonable to consider clinical trials at every stage in your cancer journey.

What Every EGFR Patient Needs to Know:

• Before you agree to any treatment plan, make sure you ask your doctor for complete biomarker testing.
• It might be possible for you to have your biomarker testing done with a simple blood test. Make sure to ask if you would be a good candidate for this.
• The initial treatment for your lung cancer may stop working for you over time, but there are other treatments that are either already approved or that are in clinical trial to help you.
• Don’t stop learning! Stay up to date with what every EGFR patient needs to know. Bookmark lcfamerica.org!

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