Jared Weiss, MD
Liquid biopsies offer an alternative method for detecting molecular mutations in patients with non–small cell lung cancer (NSCLC), according to expert Jared Weiss, MD.
“Every patient with nonsquamous disease should have comprehensive testing and go back to do repeat tissue biopsies when necessary,” explains Weiss.
In an interview during the 2017 OncLive
State of the Science SummitTM
on Advanced Non–Small Cell Lung Cancer, Weiss, an assistant professor at the UNC Lineberger Comprehensive Cancer Center, discussed utilizing liquid biopsies for patients with lung cancer, the pros and cons of the approach, and when it might be appropriate to rebiopsy patients.
OncLive: When is it appropriate to use a liquid biopsy?
: Molecular information has become key to optimal treatment of patients with stage IV NSCLC. When we match the target with targeted therapy, we get treatments that are less toxic, more effective, and demedicalize the life of the patient because they are oral and not intravenous. This makes them highly desirable.
Data from the Lung Cancer Mutation Consortium show us that just having a mutation is not good enough. If patients have mutations and it is not actionable, their survival is no better than patients without mutations. In contrast, for patients with actionable mutations, we expect dramatically greater survival than we used to expect. We are counting in years now.
I discussed when to use liquid testing and when to use tissue testing. These are complementary strategies with unique advantages and disadvantages. For the patient at initial diagnosis, we need a tissue biopsy to establish that the patient has lung cancer and that it is stage IV. There should be tissue at diagnosis when there is optimal stewardship of that tissue, including good communication between whoever is doing the biopsy, the medical oncologist, and the pathologist.
In the frontline setting, it would be optimal if we could have enough tissue to run PD-L1 and molecular testing on that initial biopsy. That is the ideal world. However, we do not always live in an ideal world for a variety of reasons. We often do not have enough tissue. With upfront testing, if the initial tissue is inadequate for comprehensive molecular testing, a liquid biopsy can then come in to supplement this.
There are different panels being done, but you want to make sure that the panel is sensitive for EGFR
, and ROS1
. When you get back an actionable molecular result, you can believe it. If you get back an EGFR result, the right clinical thing to do is to put the patient on an EGFR tyrosine kinase inhibitor (TKI). In contrast, negative results cannot be completely believed. There are all kinds of variables, including the tumor not shedding DNA into the blood in a detectable way, that can yield a negative result, even if that mutation is present inside the patient's cancer.
In this scenario when tissue is inadequate, a liquid test is done, and it does not yield an actionable result, then it is often appropriate to go back and pursue the tissue again more aggressively. The other place we think about liquid biopsies is to define the mechanism of resistance at progression. For example, if a patient is on erlotinib (Tarceva), gefitinib (Iressa), or afatinib (Gilotrif) and the cancer begins to progress, we know that, 50% or 60% of the time, the molecular mechanism is a secondary mutation, such as T790M, which is detectable and can be treated with a targeted therapy.
The right thing to do is to find out if T790M is present. One strategy that is gaining favor is to start with a liquid-based test. I tend to prefer a PCR-based test for speed. You can receive the results of the test a few days to 1 week later if you find that T790M is present.
If a patient has positive results, it has been well established that you can [act on] it. A patient can go on the 1 FDA-approved drug, osimertinib (Tagrisso), with expected outcomes that we know are superior to chemotherapy. In contrast, if you do not find T790M, then a tissue biopsy is appropriate. This can be useful to look for T790M and other mechanisms of resistance that may be actionable.
What are the advantages and disadvantages of liquid biopsies?
Tissue and blood offer distinct advantages and disadvantages. Pre-analytical variables are particularly important for liquid biopsies beyond the scope of our conversation and need to be paid attention to.
With tissue biopsy, the advantages are greater sensitivity for the spot where you put the needle. However, a disadvantage is that you must put a needle into a patient. There are risks, discomforts, and time delays associated with tissue biopsy. Additionally, there can be heterogeneity both within a tumor and within different locations. A tissue biopsy only tells you about where you put the needle.