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Liquid biopsy can noninvasively detect, monitor NSCLC
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Liquid biopsy is an effective complement or alternative to standard tissue biopsy for the detection and monitoring of clinically relevant mutations in patients advanced non–small cell lung cancer, according to study results published in Clinical Cancer Research.
Researchers obtained 112 plasma samples from 102 prospectively enrolled patients with advanced NSCLC. Patients’ plasma samples were exposed to ultra-deep sequencing of up to 70 genes and matched with tissue samples when possible.
Tissue biopsy was successfully obtained for only about half of the patient population, whereas liquid biopsy was obtained from all patients. Moreover, liquid biopsy allowed for improved patient management and serial sampling to monitor disease progression and clonal evolution, according to Erica L. Carpenter, MBA, PhD, research assistant professor in the department of medicine and director of the Circulating Tumor Material Laboratory at Perelman School of Medicine at University of Pennsylvania, and Jeffrey C. Thompson, MD, of the division of pulmonary, allergy and critical care medicine and Thoracic Oncology Group at University of Pennsylvania.
Carpenter and Thompson spoke with HemOnc Today about the study results and the potential clinical benefits of this approach.
Question: What prompted you to conduct this study?
Carpenter : It was a confluence of a number of factors. Liquid biopsies have been increasingly adopted as a way to provide additional information to clinicians as they are making decisions about their patients. As we looked at our various patient populations, one thing we have noticed, especially for our patients with NSCLC, was that the number of approved targeted therapies has really increased in recent years. These targeted therapies are directed against mutations in certain genes, so we need a way, in real time, to be able to monitor whether a patient’s tumor expresses that mutation so we can make a decision in the clinic about how best to treat that patient. This all came together in this feasibility study. We wanted to answer a very fundamental question of whether liquid biopsy could be used to detect these targetable mutations.
Thompson : With these molecular agents, there are certain resistant gene mutations for which we now have approved drugs. Liquid biopsy really could allow for the detection of these resistance mechanisms and may sometimes obviate the need for tissue biopsies, which can be very challenging in patients with lung cancer as their disease progresses.
Q: What did the findings suggest?
Carpenter: We were interested to see how feasible it was to use liquid biopsy. Our findings suggest that a liquid biopsy can certainly be complementary to a tissue biopsy and, in some cases, even more suitable than a tissue biopsy for monitoring patients with advanced disease. Among the 102 patients enrolled and for whom liquid biopsy was completed, we were only able to obtain a tissue biopsy for about half of those patients. In the half of patients for whom no tissue biopsy was obtainable, liquid biopsy turned out to be the only way to effectively detect mutations to help inform clinical decision-making in those patients with respect to targetable therapies. The study answered the question not only of feasibility, but suggests that liquid biopsy can add additional and unique information for these patients. This is information that, for half of our patients, would otherwise not have been available. From the patient perspective, liquid biopsy is a simple blood draw. Compared with a tissue biopsy, it is a noninvasive procedure. It does not have the inconvenience and pain typically associated with a tissue biopsy.
Q: How does the technique work ?
Carpenter : We draw a small amount of blood from the patient. The blood is processed in a clinical lab. The plasma — where the circulating tumor DNA is known to reside — is spun off. The DNA is extracted, quantified and taken to the sequencer. Sequencing is conducted for mutations in 70 genes selected for their known role in various cancers. Once this sequencing has been conducted, a physician’s report is issued that contains a listing of each of the mutations, as well as the frequency of each mutation.
Q: What promise does liquid biopsy potentially hold for these patients?
Carpenter : Liquid biopsies provide clinically important information in the case when a tissue biopsy is not available or obtainable. This information can be used to make decisions about therapy. Future studies will focus on whether use of these tests are associated with improved patient outcomes, and this is an area of active interest for us.
Thompson : One might envision particularly for patients who progress on chemotherapy or targeted therapy, that one could utilize a noninvasive technique to screen patients for an actionable mutation prior to taking another biopsy to detect a resistance mutation.
Q: How does this fit in with the national cancer moonshot initiative?
Carpenter : Vice President Biden was at Penn when he launched the initiative, and our cancer center director — Chi Van Dang, MD, PhD — is a member of the blue ribbon panel that presented a report to the National Cancer Advisory Board as part of the moonshot initiative. There are many places throughout the blue ribbon report where liquid biopsies can play a role. One of the urgent unmet needs is being able to accurately predict when a patient may develop drug resistance. This is important for many reasons. It is thought that liquid biopsies may eventually be able to detect resistance to therapy earlier than imaging. It is also important because, in the case of certain targeted therapies, we have additional drugs known as second- and third-line inhibitors that can be used to target a resistance mutation detected by a liquid biopsy. The physician may then switch the patient’s therapy to target that specific mutation. We are continuing to design studies and think of new ways in which liquid biopsy could address unmet needs.
Q: Is there anything else that you would like to mention ?
Carpenter : Our group has more than a dozen liquid biopsy studies ongoing in many different cancers. This particular study reconfirms our conviction that these assays will have relevance for other types of cancer, which we are actively pursuing. Also, in this particular study, we focused on a heavily pretreated population. We next want to consider the value of a liquid biopsy as a complement to tissue testing at diagnosis. In other words, what is the value of a liquid biopsy before a patient has had any therapy? I think our study is promising in this regard, but we need to define the study that will precisely answer this question. We are working on this.
Thompson : With new technology and noninvasive liquid biopsies, we are starting to hone in on precision medicine for an individual patient. For several cancer types, the number of patients who have a targetable drug is expanding quite rapidly. It is important to develop these technologies and study them in a clinical setting to determine their relevance and impact on patient outcomes so we can bring all of these technologies together and really treat the individual patient to obtain the best outcomes possible. – by Jennifer Southall
For more information:
Erica L. Carpenter, MBA, PhD, can be reached at University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104; email: erical@upenn.edu.
J effrey C. Thompson, MD, can be reached at University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104.
Reference:
Thompson JC, et al. Clin Cancer Res. 2016;doi:10.1158/1078-0432.CCR-16-1231.
Disclosure: Carpenter and Thompson report no relevant financial disclosures.