Associate Clinical Professor, Division of Hematology/Oncology, Medicine

 [Turning to] the structure, I know this isn’t what the guidelines recommend. They still de-emphasize liquid testing—more in a second—and reflex testing with some exclusions. In a real-world setting, there are so many obstacles to obtaining appropriate tissue at the time of first visit that it’s just a simple clinical requirement for us to have the information as soon as possible. Liquid biopsy has filled in very nicely and has become a cornerstone of diagnostic [testing] up front.

 Yes, I agree. We’ll get Tim’s perspective on tissue, but I want to touch on liquid and get some perspectives around the room. Tim, what are your thoughts on how you incorporate ctDNA [circulating tumor DNA] in the diagnostic algorithm for patients? Then I want to get Fernando’s view on what’s done at Memorial [Sloan Kettering Cancer Center].

 Liquid biopsy has come into its own from its origin a few years ago. It’s still correct to say that tissue is superior. But we have to yield to the practicalities of patients who are difficult to get tissue from, those who recur. Often, it’s very difficult to get tissue, and those are good candidates for liquid biopsy. Some folks are doing liquid biopsy at the time of tissue biopsy and work-up because they’ll get a faster turnaround on the liquid. The tissue comes later with the results from the tissue molecular diagnostics that can help supplement the liquid biopsy results.

 Hatim, what’s your perspective on how to incorporate liquid biopsies at UCSD [University of California San Diego] and how you’re using it in the diagnostic algorithm?

Thank you, Ben. Tim gave a wonderful answer. To add to it, I’ll say that we do liquid biopsy up front. We think liquid biopsy is an essential component of diagnostic testing, largely because of the turnaround time that can be achieved. With more sophisticated technologies, there’s good concordance from tissue to liquid. When there isn’t concordance, if we get a negative liquid test, we emphasize reflexing the tissue and not forgetting about the tissue as the gold standard.

 I agree. A negative tells you nothing. The sensitivity of liquid is around 70%. You get a 30% false negative, and a positive essentially rolls in. But at Johns Hopkins we’ve bought into the algorithm and drunk the Kool-Aid of using liquid with tissue. Given the challenges of tissue, we can talk about it later in this section.

Fernando, how are you routinely using liquid at Memorial? Is it every patient? I know you have an in-house liquid test. You have MSK-IMPACT, the tissue test. How do you molecularly profile patients?

 We have 2 broad and very good panels: MSK-IMPACT, which is the tissue NGS [next-generation sequencing], and a smaller but still very broad panel, MSK-ACCESS, for NGS and ctDNA. Fortunately, it reflects every lung cancer histology. [For tissue testing], non–small cell lung cancer goes to MSK-IMPACT reflexively. At every new visit, we try to collect with MSK-ACCESS the ctDNA as well. We’re trying to do as well like the Idylla for ctDNA for 

, which can sometimes be even 1 day or a few hours in turnaround time. With a good amount of patients, we can start treatment fast with the Idylla ctDNA, where it’s complementary. We’re trying to do both platforms in the first visit.

 All of us have started to do this. I want to reserve the challenges of tissue for the end, not only in the academic setting but in the community setting as well. Maybe we can revisit liquid in the context of those challenges.

Videos

Experts in lung cancer explain their views on the critical role of liquid biopsy in molecular testing in non–small cell lung cancer.

Liquid Biopsies in the NSCLC Molecular Testing Algorithm

® program titled “Actionable Mutations In Non–Small Cell Lung Cancer: Expert Perspectives in Testing and Targeted Therapy.” I’m Dr Benjamin Levy, and I’m an associate professor at Johns Hopkins School of Medicine [in Baltimore, Maryland] and the clinical director for the Johns Hopkins Sidney Kimmel [Comprehensive] Cancer Center at Sibley Memorial Hospital in Washington, DC. I’m joined by a panel of experts in the field of lung cancer. We have a lot of complexity to distill. It’s gotten complicated. This complicated field has generated a tremendous amount of enthusiasm, but it’s always nice to hit the pause button and review the data that we have so far with genotype-directed therapies, which have been on the leading of edge lung cancer and solid tumor oncology. I’d like to welcome my esteemed fellow panelists to introduce themselves.

 Hi, I’m Misako Nagasaka. I’m an associate clinical professor at the University of California, Irvine, School of Medicine, and I specialize in thoracic malignancies. I’m excited to join the discussion. Thank you for having me.

 Thank you. I’m Tim Allen, a professor and the chair of pathology at the University of Mississippi Medical Center [in Jackson, Mississippi]. I’m a pulmonary pathologist. This is going to be a great discussion.

 Good evening, everybody. I’m Martin Dietrich from Florida Cancer Specialists & Research Institute and the University of Central Florida [Lake Nona] Cancer Center [in Orlando, Florida]. I’m an assistant professor, and I specialize in genetics and thoracic oncology.

Hello, everyone. It’s a pleasure to be here. My name is Hatim Husain. I’m a medical oncologist at the University of California San Diego. I’m an associate professor in the School of Medicine. I focus on lung cancer, genomically oriented therapies, and immunotherapy.

 Hi everyone, I’m Fernando Santini. I’m a thoracic oncologist at Memorial Sloan Kettering Cancer Center in New York [New York]. It’s a pleasure to be here.

 Welcome, everyone. Thank you for joining me. We’re going to discuss a number of updates in advanced non–small cell lung cancer. We’re going to discuss the data in the context of national and international guidelines, and the evolving treatment landscape and its impact on clinical practice. We can all agree that lung cancer has been the poster child for precision medicine. We’re going to review a lot of those data as they relate to not only medical oncology decision but also tissue interrogation. From the pathology side, we’ll get input on how these are best identified.

Let’s get started with our first topic. Chapter 1 of this personalized medicine story in lung cancer is probably 

 and all these others, let’s take a step back and talk about how we test for these and what we’re looking for. Clearly, 

 are chapters 1 and 2. But there are other alterations that have been discovered that are targetable that we can wed to genotype-directed therapies. It has changed the outcomes for our patients. It has improved outcomes in terms of not only PFS [progression-free survival] but also OS [overall survival], and perhaps underrepresented is quality of life. We’ve come a long way from 

. We have 9 and are maybe going to have 10 actionable mutations in lung cancer. In the next maybe 6 months, we’ll get another approval.

Misako, I’ll start with you. What are you testing for? What do you routinely test for at your center? How do you go about doing that?

 This is a very important topic. Guidelines recommend routine testing at the time of advanced metastatic diagnosis of all patients with non–small cell lung cancer with adenocarcinoma histology for 

, and that’s what I test for as well. It’s important to note that the NCCN [National Comprehensive Cancer Network] panel strongly advises broader molecular profiling, with the goal of identifying rare driver mutations for which effective drugs may already be available, or to appropriately counsel patients regarding the availability of clinical trials. I agree that broad molecular profiling is the key component of improvement of care of patients with non–small cell lung cancer.

 At your centers, I assume that this isn’t a single gene test but that you’re doing comprehensive genomic profiling. Is that correct?

 Shifting to Martin, there are a lot of questions about how this is done. We want to do comprehensive genomic profiling, but is this done reflexively at your institution? Do you have to get the medical oncologist to order it? How do you carry this out?

 We have 2 major hospital systems we’re working out of. One has established a reflex protocol on an Oncomine panel for 50 genes, which is a very efficient way of obtaining genomic results. We’ve been talking about advanced lung cancers. As you know, genomic testing and guidance has found its way into early stages as well, starting in stage I in the setting of adjuvant 

 and immunotherapy targeting. This is affecting early stage disease as well. For the most part, this remains an on-demand testing that we do on an NGS [next-generation sequencing] platform with both DNA and RNA chips. We’re trying to be as comprehensive as possible, but it typically defaults to our medical oncologists to obtain these tests upon seeing the patients in the first visit.

There are many reasons, which we’ll get to later, regarding why we don’t have reflexive testing through the many channels that we’re seeing those patients. It brings us to the question of how best to test. How we’re doing it is typically a question of what’s pragmatically done and scientifically pure. We all agree that tissue-based testing for the time being remains the gold standard when it comes to the sensitivity of testing. But for pragmatic reasons, including tissue availability and turnaround time, we’ve adopted a pattern where we integrate liquid biopsy in a virtually synchronous fashion of ordering at the time of first visit with patients to ensure that patients have at least the best attempt of having NGS results available at the time of initiation of therapy.

Oncologists provide insight into what actionable mutations they look for when they order molecular testing for patients with advanced non-small cell lung cancer.

Testing Approaches for Actionable Mutations in NSCLC in Clinical Practice

Martin Dietrich, MD, PhD, assistant professor, University of Central Florida, fellow, American College of Physicians, Florida Cancer Specialists & Research Institute, discusses future research directions for the treatment of patients with lung cancer. 

A potentially practice-changing trial is the ongoing phase 3 LAURA study (NCT03521154), which is examining the efficacy and safety of osimertinib (Tagrisso) following chemoradiation in patients with stage III unresectable non­–small cell lung cancer (NSCLC) whose tumors harbor 

 mutations, according to Dietrich. Based on data from the phase 3 PACIFIC trial (NCT02125461), it is clear that this subset of patients derives some benefit from additional treatment in this setting, Dietrich adds.

Martin Dietrich, MD, PhD, discusses future research directions for the treatment of patients with lung cancer. 

Dr. Dietrich on Future Research Directions in Lung Cancer 

Martin Dietrich, MD, PhD, medical oncologist, Advent Health Cancer Institute, discusses management of diarrhea, an associated adverse event (AE) of neratinib, following data from the CONTROL trial in patients with HER2-positive breast cancer.

Diarrhea is the most common on-target effect of neratinib treatment. When Dietrich speaks to patients who are about to go on neratinib, he informs them about the side effects that need to be recognized, specifically mentioning diarrhea. For patients who have had neratinib recently, Dietrich talks about the additional strategies to control the diarrhea. According to Dietrich, the body undergoes an adjustment and the diarrhea become less frequent and less intense.

Based on the CONTROL trial results, Dietrich's practice adopted a combination of loperamide and colestipol, sometimes adding budesonide, as a baseline regimen to control the diarrhea AE, which is cost-effective and tolerated by patients. The mechanism causing the diarrhea, whether inflammatory or secretory, is not currently known. However, results suggest it is a combination of both factors.

Martin Dietrich, MD, PhD, medical oncologist, Advent Health Cancer Institute, discusses management of diarrhea, an associated adverse event of neratinib, following data from the CONTROL trial in patients with HER2-positive breast cancer.

Martin Dietrich, MD, PhD

Articles

Liquid Biopsies in the NSCLC Molecular Testing Algorithm

Testing Approaches for Actionable Mutations in NSCLC in Clinical Practice

Dr. Dietrich on Future Research Directions in Lung Cancer

Dr. Dietrich on Optimal Adverse Event Management for Neratinib in Breast Cancer