Biomarker testing and targeted treatments have contributed to improved outcomes for people with lung cancer. However, not enough people are undergoing comprehensive biomarker testing.
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 there are several targeted treatments available. There are even more potential treatments in the works.
“Lung cancer is no longer just one disease. [I]t’s 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 Dr. Evangelist, whose focus is lung cancer. “So, it’s 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 Dr. 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 Dr. Evangelist. “It means we are not identifying these mutations in patients. That’s problematic because [they] aren’t 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 have a treatment available. Still, it is important to determine the subtype of lung cancer they have.
“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 Dr. Evangelist. “I might have tested [someone] a year ago and it might be a new biomarker and now there’s an FDA [Food and Drug Administration]-approved treatment. If I didn’t do the testing, I wouldn’t 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 Dr. Evangelist. “And that’s when we give the [person] the right drug.”
Treatment options for NSCLC depend on the stage of the cancer and the biomarkers. Doctors rarely find NSCLC in the early stages. For this reason, much of the research focuses on targeted treatment in stages 3 and 4. Better screening is necessary so that doctors can catch NSCLC earlier. Targeted treatment could also make a big difference in the earlier stages of lung cancer.
Inhibitor medications directly target specific gene mutations to shut them off. This can stop or at least slow down the growth of cancer cells.
These medications can be effective for a while, but they may stop working after months or years.
Dr. 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’s in a different gene that actually has a targeted agent.”
Doctors should repeat biomarker testing when that happens. Testing may show why the treatment is not working. There may be a new tailored treatment available that is a better match for the person’s NSCLC subtype.
One exciting advancement is the use of liquid biopsy to learn more about tumors. In liquid biopsy, a doctor takes a blood sample to find out more about the DNA of the tumor. This reduces the amount of tissue needed to test for multiple biomarkers.
It can also improve rates of testing. Dr. Evangelist feels optimistic about the future of biomarker testing. “We’re hoping to see an uptick in [the] utilization of liquid biopsy. Liquid biopsy can look for all of those driver mutations.”
Liquid biopsy gives information about a person’s outlook and how the tumor may respond to treatment. Even very good treatments 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, though the immunotherapy response test is often the first test to come back. It is important for a person and a doctor to have a conversation about the best treatment option for them.
So far, PD-L1 is the most common biomarker used to guide decisions about immunotherapy. “It does help guide treatment, but it’s not the full story,” said Dr. Evangelist.
Additional mutations can identify people who may be less likely to respond to immunotherapy. One of these is KEAP-1. There is a trial underway called the KEAPSAKE trial to explore why some people do not respond to first-line treatments.
For those with PD-L1 mutations, PD-1 or PD-L1 inhibitors can help the immune system destroy cancer cells. This can shrink or slow the growth of tumors. PD-1 or PD-L1 inhibitors may help even if PD-L1 biomarkers are not present.
One study showed benefits with a combination of nivolumab (Opdivo) and chemotherapy. This combined treatment was more effective at shrinking tumors than chemotherapy alone.
Early trial results show promise for EGFR mutations that no longer respond to osimertinib. Osimertinib is one of the first-line targeted treatments. In the study, 36% of participants responded to a combination of amivantamab and lazertinib.
Scientists are now trialing a targeted treatment for people with RET gene mutations.
Another study looked at people with stages 1B to 3A NSCLC with EGFR mutations. Those who received osimertinib lived significantly longer than those who received a placebo. This is promising, but it also requires doctors to catch NSCLC in its earlier stages.
The MET exon 14 skipping mutation occurs in 3–4% of people with NSCLC. About half of those who received tepotinib in a study had some response to this treatment.
Biomarker testing is a way to learn more about genetic changes that may be present in cancer cells. With this information, there are often more targeted treatment options available.
Advances in biomarker testing, especially through liquid biopsy, are improving treatment options.