Key takeaways
- Comprehensive biomarker testing remains underutilized, with research showing only 46% of people with non-small cell lung cancer receive extensive testing despite 90% being tested for at least one biomarker.
- Targeted therapies can be effective for months or years, but cancer cells may eventually develop resistance mechanisms that require repeat biomarker testing to identify new mutations and guide alternative treatment options.
- Liquid biopsy is an emerging tool that analyzes blood samples for tumor DNA fragments, making biomarker testing more accessible when traditional tissue biopsies are difficult to obtain and helping monitor treatment response over time.
Biomarker testing is also known as molecular or genetic testing, and it can tell doctors more about the specific subtype of lung cancer a person has.
There are several types of non-small cell lung cancer (NSCLC), and several targeted treatments are available. Plus, even more potential treatments are in the works.
“Lung cancer is no longer just one disease. [I]t is really a group or family of lung cancers,” oncologist Dr. Makenzi Evangelist told Medical News Today. “Each one of them is driven by different genetic changes.”
Along with staging and identifying the type of lung cancer a person has, genetic testing allows oncologists to understand the subtype.
“We know that certain treatments are going to be highly effective in certain subtypes of lung cancer but very ineffective in others,” said Evangelist, who specializes is lung cancer. “So, it is critical to know what the testing is showing so we pair the patient with the right medications.”
A person should undergo biomarker testing before any treatment starts. It may take 5 weeks from diagnosis to the first treatment, said Evangelist. This wait can be difficult for the person and for their loved ones.
“I think everybody feels like, ‘I have cancer. I need to start [treatment] yesterday.’ But the last thing we want to do is to start just anything. We need to start [a person] on the right drug,” she said.
There are several gene mutations that can occur in NSCLC. Within each of these genes, there can be different types of mutations. Genes are like an instruction manual for the cell. When there is an error in the instructions for the cell, it does not grow normally. This can lead to cancer.
With genetic testing, doctors can find out more about what problem caused the cancer. With this information, they can use medications and therapies to target the problem.
In NSCLC, several genes can have mutations that lead to abnormal cell growth. EGFR and ALK gene mutations are most common.
In a perfect world, everyone with NSCLC would undergo full biomarker testing. However, research indicates that this is not always the case.
A study that took place between April 2018 and March 2020 looked at over 3,000 people with NSCLC across the country to see how often individuals underwent biomarker testing. It found that 90% of people were tested for at least one biomarker but that only 46% of people had extensive biomarker testing.
“The results were pretty disappointing,” said Evangelist. “It means we are not identifying these mutations in patients. That is problematic because [they] are not getting the opportunity to get the right drug or the opportunity to enroll in a clinical trial.”
Sometimes, the genetic markers a person has do not yet have a targeted treatment. Still, identifying the subtype of lung cancer is important for guiding care.
“The panel testing is so important, not just for what we know, but because these mutations are being identified quickly and new treatments are coming out,” said Evangelist. “I might have tested [someone] a year ago and it might be a new biomarker and now there is an FDA [Food and Drug Administration]-approved treatment. If I did not do the testing, I would not know.”
Biomarker testing is making a big difference in the survival of people with NSCLC. Mortality rates from NSCLC decreased between 2013 and 2016. Part of this is that fewer people are receiving diagnoses of NSCLC. Targeted therapies have also played a part in helping lower mortality rates.
“We have people living [for] years with advanced lung cancer,” said Evangelist. “And that is when we give the [person] the right drug.”
Treatment options for NSCLC depend on the stage of the cancer and the biomarkers found in the tumor. Many cases are still diagnosed at later stages, although improved screening is helping doctors detect more cancers earlier.
Historically, much of the research has focused on targeted treatment for stages 3 and 4. However, researchers are increasingly studying how targeted therapies may benefit earlier-stage disease, as well.
Targeted inhibitor medications block specific gene mutations that drive cancer growth. By shutting off these signals, they can stop or at least slow down the growth of cancer cells.
These medications can be effective for months for even years, but they may eventually stop working.
Evangelist explained why this happens. “We know that if [someone received] an oral targeted agent that, over time, their genetic makeup can evolve. So, they can develop resistance mechanisms either in the same gene, like [the] EGFR or ALK gene, or in other genes. And, in some cases, it is in a different gene that actually has a targeted agent.”
When this happens, doctors should repeat biomarker testing. New testing may reveal additional mutations that explain why the treatment is not working and help identify other available targeted treatment that may now be a better match.
One exciting advancement is the use of liquid biopsy to learn more about tumors. In liquid biopsy, a doctor takes a blood sample to look for pieces of tumor DNA circulating in the bloodstream. This can provide information about the genetic changes in a tumor while reducing the amount of tissue needed for biomarker testing.
Liquid biopsy can also help improve testing rates, especially when it is difficult to obtain enough tumor tissue for a traditional biopsy. Evangelist feels optimistic about its use. “We are hoping to see an uptick in [the] utilization of liquid biopsy. Liquid biopsy can look for many of those driver mutations.”
In addition, liquid biopsy may provide clues about how a tumor is responding to treatment and a person’s outlook. Even highly effective therapies do not work for everyone.
“If [people] still have detectable DNA, then their treatment [can be] tailored because they are likely to be at higher risk for progression. It lets us make sure we tailor that approach to the patient,” said Evangelist.
There is hope for the use of immunotherapy in NSCLC, but more progress needs to be made. Immunotherapy is not right for everyone, so it is important for a person and their doctor discuss the best treatment approach for them.
PD-L1 is currently the most common biomarker used to guide decisions about immunotherapy. “It does help guide treatment, but it is not the full story,” said Evangelist.
For those with PD-L1 mutations, PD-1 or PD-L1 inhibitors may help the immune system destroy cancer cells. This can shrink or slow tumor growth. In addition, some people may benefit from these drugs even if PD-L1 biomarkers are low or absent.
Researchers are also
Some people who have NSCLC may benefit from combination therapy, which pairs different types of treatments to improve outcomes.
For example, results from one study showed that combining nivolumab and chemotherapy was more effective at shrinking tumors than chemotherapy alone.
Combination therapy is also being explored for to treat tumors that develop resistance to first-line targeted treatments. For example, in early trial results for people with EGFR-mutated NSLC no longer responding to osimertinib, a first-line targeted treatment, about 36% of participants responded to a combination of amivantamab and lazertinib.
These results are promising and suggest that combination approaches may help improve outcomes and overcome treatment resistance in some people with NSCLC.
Scientists are now developing targeted treatments for additional genetic changes in NSCLC. For example, therapies are in clinical trials for people whose tumors have RET gene mutations, offering a new option for this subgroup.
Early-stage NSCLC may also benefit from targeted therapy. In a study of people with stages 1B to 3A EGFR mutations, those who received osimertinib lived significantly longer than those who received a placebo. These results are promising, but also highlight the importance of detecting NSCLC in its earlier stages.
The MET exon 14 skipping mutation occurs in 3–4% of people with NSCLC. In clinical trials, about half of those treated with tepotinib had some response to this treatment. This demonstrates that targeted therapies can be effective for even less common mutations.
Biomarker testing helps doctors understand more about the genetic changes that may be present in a person’s cancer cells. This information can open the door to more targeted treatment options tailored to the tumor’s specific characteristics.
Recent advances are making it easier to test for multiple biomarkers, monitor how cancer responds to treatment, and improve outcomes by helping doctors make more informed, personalized treatment decisions.