Until a little over a decade ago, all types of NSCLC were essentially treated in the same way, typically with chemotherapy. However, now specific types of NSCLC can now be managed based on the biomarkers that characterize them. Biomarker testing, which is sometimes called genomic or molecular testing, looks for changes in a tumor’s DNA, or genetic makeup, according to the American Lung Association (ALA). When these biomarkers are identified, doctors can now match the type of NSCLC you have with the treatments that will provide you with the most benefit, potentially improving or extending your life with the disease, the ALA says.
The Role of Biomarkers in NSCLC
There are several biomarkers used to determine treatment in NSCLC. These include gene mutations in tumor cells such as EGFR, ALK, BRAF, ROS1, MET, RET, KRAS, HER2, and NTRK that can be “targeted” by specific cancer drugs called targeted therapies. Targeted therapies are specific drugs that “target” cancer cells with alterations in specific genes, leaving healthy cells more or less untouched, according to the Lung Cancer Foundation of America (LCFA). A second group of biomarkers in NSCLC are immunotherapy biomarkers such as the PD-L1 protein, the LCFA notes. This protein is known to control the body’s immune response and its presence can tell your doctor if you will respond to immunotherapy, one of the more recently approved treatments for NSCLC, which is designed to harness your own immune system to fight the cancer, the LCFA says. It’s now recognized that many patients with NSCLC have alterations in genes that drive the growth of their cancer, according to research published in the April 2021 edition of the World Journal of Clinical Oncology. In recent years, more and more of these drivers of gene mutations have been identified, and a better understanding of the biology of these genes has allowed for the development of new targeted therapies. “I explain these biomarkers to patients as kind of like the Achilles’ heel of a cancer,” says Zosia Piotrowska, MD, an oncologist at Massachusetts General Hospital and an assistant professor at Harvard Medical School in Boston. “When we can find them, we can treat them with a targeted therapy in some cases.”
Testing for Gene Alterations
Biomarkers in NSCLC are found through a technology called Next Generation Sequencing (NGS), Dr. Piotrowska notes. This test looks for genetic alterations – things like gene mutations, fusions, or rearrangements. All of these factors together help to narrow down the type of disease that doctors are dealing with, and the treatment they will choose to attack the cancer. “Molecular testing is so important in NSCLC because it helps us to really understand the specifics of a patient’s lung cancer, sometimes the reasons that a lung cancer developed, and most importantly, it helps us select the best therapy for patients,” Piotrowska says.
How Is Testing Conducted?
Biomarker testing in NSCLC is done either with a biopsy (a tissue sample from a tumor, collected during a minor surgical procedure) or a blood test called a liquid biopsy or plasma test, according to Piotrowska. In a liquid (blood) biopsy, your oncologist will extract samples of your blood cells for analysis. The process, which is similar to how blood is collected for routine testing, is noninvasive, she says. From collected samples, pathologists work to isolate the DNA from the cancer cells and perform NGS to look for specific mutations or alterations, Piotrowska says. Liquid biopsies are becoming more commonplace in NSCLC and in some cases are used in place of traditional tissue biopsies, she adds. These biopsies look for circulating tumor DNA that have been shed by cancer cells into a patient’s bloodstream. Pathologists can then isolate those DNA fragments and conduct sequencing to look for specific changes in genes. It can take up to four weeks to get the results from a biomarker test, but taking this time helps your doctor complete your diagnosis.
Targeting Gene Alterations
Once testing is conducted and genetic alterations are identified, doctors can work to develop a treatment plan that is specifically designed to target those alterations, Piotrowska explains. “The reason that molecular testing is so important is that patients who have an alteration in one gene are likely to benefit from one targeted therapy, whereas patients who don’t have an alteration in that gene are not going to respond to that targeted therapy,” she notes. “Again, the goal of this type of testing is to identify everything we can about the cancer to try to select the best and most effective therapy for that patient.” The first mutation researchers determined could be treated with targeted therapy in NSCLC was a mutation in the epidermal growth factor-receptor (EGFR) gene, according to the ALA. Once doctors realized that patients with this type of mutation could be effectively treated with EGFR-targeted therapies, research turned toward identifying other targetable mutations. Approved targeted therapies now exist for an increasing number of biomarkers, including EGFR, ALK, ROS1, BRAF, MET, RET, NTRK, HER2, and most recently, KRAS, the ALA says. However, it’s important to note that not everyone with NSCLC will have an alteration that can be treated with a targeted therapy. In addition, another medical condition may make some patients ineligible for these treatments, due to potential side effects. Just as the presence of genetic alterations helps doctors to narrow down which treatment will likely benefit a patient most, the absence of those alterations also serves to inform a person’s course of treatment, Piotrowska says. And since research in NSCLC is constantly advancing, the more knowledge a doctor has about their patient’s cancer, the more able they are to potentially match their patients to emerging treatments. These patients may have some other biomarkers for which there is a clinical trial available, for example. Having one particular genetic alteration isn’t necessarily better or worse than having another, but some do have more therapeutic options, Piotrowska notes. Knowledge of the presence or absence of these alterations also tells doctors what not to do. For example, certain treatments, like immunotherapy, are going to be less effective for cancers with particular alterations like EGFR and ALK, she says. “Some have been known about for longer, such as EGFR and ALK, and some are more recent discoveries and have only recently had approved targeted therapies, so varying numbers of treatment options exist for each of these oncogenes, but I hope that will change in the future,” Piotrowska adds. “But I think at the end of the day, the best thing for each individual patient is to do the appropriate testing.”
When Should Testing Be Done?
The best time for molecular testing is at the time of initial diagnosis. “The goal is to have this information as quickly as possible to help us select the best treatment for that patient,” advises Piotrowska. For some patients, molecular testing will have to be repeated later in the treatment course to modify therapy as needed, particularly if the tumor stops responding to the current regimen, according to the National Comprehensive Cancer Network (NCCN).
What Comes After Testing?
Receiving the results of molecular testing can often take up to a few weeks, and you may be asked to wait for these results to return before treatment can be started. Piotrowska acknowledges that this can be an incredibly difficult time for you and your family, particularly if you’ve just been told you have NSCLC. Understandably, you may be anxious to start treatment, she says. Even so, she encourages those diagnosed with the disease to ask plenty of questions of their doctors during this process, especially since the results of these tests may or may not be routinely shared with you. “It’s important for patients to feel empowered,” Piotrowska says. “Ask your providers about what type of testing was done, what was learned about your cancer, and finally, how that will impact treatment decisions going forward.”
