How Biomarkers Impact Treatment Decisions in Lung Cancer

January 28, 2021
Conor Killmurray

Biomarkers play an important role in treatment decisions of many tumors, but in lung cancer they are a deciding factor between which immunotherapy is the best option.

Treatments for lung cancer have recently become more personalized thanks to the increasing study and use of biomarker testing in patients prior to immunotherapy treatment. Biomarkers provide clinicians with insight as to what treatments may work best, and the widespread use of biomarker testing is helping to drive treatment decisions and improve outcomes.

At the CURE® Educated Patient® Lung Cancer Summit, Dr. Melissa Johnson discussed the different types of biomarkers that are driving decisions for patients with small cell lung cancer (SCLC). Her main focus was on the widespread PD-L1 tumor mutation burden and microsatellite instability (MSI) that are known for their roles in other cancers but play an important role in determining immunotherapy treatment for patients with SCLC.

In an interview with CURE®, Dr. Johnson, director of the lung cancer program at the Sarah Cannon Caner Center in Nashville, Tennessee, discussed how these biomarkers help drive treatment decisions.

CURE®: Can you explain what a biomarker is and what you look for when you take a biopsy?

Johnson: The way I explain this to my patients is those immunotherapy biomarkers are indications on the tumor tissue, that the immune system knows that the cancer is present. If we take a step back, your immune system should recognize the cancer because it's foreign to your body just like your immune system recognizes viruses, bacteria, or other foreign invaders. So when a cancer is able to grow, there's something that is evading the normal immune system surveillance.

The way these immune therapy drugs work, they boost a patient's own immune system but what we know is that if the immune system doesn't recognize the cancer, (and) if the immune system is ignoring the cancer, then these therapies won't work. So, the biomarkers indicate that a patient's immune system knows that the tumor is there; that there's just something impeding the immune system's ability to attack. And those are patients in whom immune therapies are likely to bring benefit to, when the immune system is able to recognize it and go after it.

How are markers like PD-L1 and MSI linked?

They are related. Microsatellite instability, you can think of as a super, super high tumor mutation burden. Tumor mutation burden is scoring a likelihood based on a particular tumor, that they'll be neo-antigens in the tumor that the immune system can recognize. And this is a calculated score that is done on next generation sequencing profiles. So, if your cancer has been profiled using Foundation One, Kerris, even Tempus, all of those vendors have the ability to calculate a tumor mutation burden score.

Then, Keytruda (pembrolizumab) is approved for patients whose tumor mutation burden is higher than 10, so that's one way that this biomarker is being used. Lung cancer is not a tumor where we check microsatellite instability, routinely, that's more often used in colorectal cancer, and has been associated with response to chemo therapies that are used for colorectal cancer. So, I would say that if you are a lung cancer patient, you should ask your oncologist about the PD-L1 biomarker and the TMB (tumor mutation burden) biomarker. The MSI microsatellite instability has also been done on your tumor if you've had next generation sequencing, but we don't talk about it quite as much in lung cancer.

What kind of immunotherapy is being given based off these biomarker tests? What is the distinction for patients with SCLC?

So, in lung cancer, we will treat tumors that express high levels of PD-L1 with immunotherapy from the outset. Firstline therapy before patients receive any chemotherapy, because if you have a high PD-L1 score, you're likely to respond. I would say that for patients that have a PD-L1 score less than 50% tumor, initially, frontline therapy will include immune therapy but likely will also include some chemotherapy.

The one exception might be that if a patient's tumor expresses PD-L1 at low levels. But TMB at higher levels is a type of cancer that is likely to respond to immunotherapy, and so, either Keytruda alone might be given, or a combination strategy like Opdivo (nivolumab) and Yervoy (ipilimumab) might be given for that type of patient. We would expect a patient who has a high level of PD-L1 or a high TMB to have rapid response after the first couple doses of immunotherapy, and what that means is hopefully declining symptoms, improving energy and improving their ability to go about the things they would like to do. It is important to know that if you have a high level of PD-L1 expression in your cancer, and you're treated with an immunotherapy, there might be a little higher risk of immune-mediated side effects, but most of those side effects are reversible with steroids.