What are lung cancer biomarkers, and how do they impact treatment options? Dr. Isabel Preeshagul defines biomarkers and explains how different biomarkers may help determine treatment options and aid in predicting treatment response.
Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul here.
Well, let’s define a few terms that are often confusing for patients. What are biomarkers?
Those are somatic alterations in the tumor just like EGFR, or ALK fusions, or MET exon 14, or MET amplification, or KRAS G12C.
These are all genes that are altered in the tumor. And these are genes that drive the tumor to grow. There are also other markers like PD-L1, which is a marker for response to immunotherapy. And there are various markers.
I could go on and talk about it for hours, but those are the more common ones that we know how to treat and how to handle and prognosticate.
And another term that’s sometimes confusing, what is a genetic mutation?
So, for genetic mutations, you have germline, and you have somatic. So, a germline mutation may be something like a BRCA1 or a BRCA2 that we see in patients with breast cancer or prostate cancer versus a somatic mutation which would be EGFR that I had mentioned or ALK fusion. So, germline mutations are the ones that we worry about being heritable.
And somatic mutations are those that are not thought to be heritable but thought to happen spontaneously within the tumor itself and cause the tumor to grow. We are constantly learning more about these though, however. But it’s really important to talk with your doctor to see if you have a germline mutation or a somatic mutation or if you have both.
And it is never wrong to seek an opinion with a genetic counselor to make sure that everyone in your family is safe, that you’re up to date on age-appropriate cancer screening, and that your family gets screened appropriately as well if indicated.
Are there specific biomarkers that affect lung cancer treatment choices?
Oh, definitely. One that I had mentioned is PD-L1. And this is a marker that we look for expression. So, based on FDA approval for pembrolizumab, if you have an expression of 50 percent or more, you are able to get immunotherapy alone in the upfront setting. If you have less than 50 percent, we often give you chemotherapy plus immunotherapy. And that’s based on a clinical trial known as KEYNOTE-189.
Other markers such as EGFR, as I had mentioned, ALK fusions, RET, NTRK, MET exon 14, ROS1, KRAS, HER2, you name it, those are alterations that we look for ideally in the upfront setting as well and can really affect treatment planning.
And those patients that harbor mutations like EGFR and ALK and ROS1 or MET exon 14, we know that these patients do better with targeted therapy upfront, not standard-of-care chemo. So, it’s really important to know about the presence of these alterations before you start treatment if possible.