Testing Matters: Practical Approaches to Biomarker Evaluation in NSCLC

Dr Jamie Chaft reviews the importance of early tissue stewardship in NSCLC, including how biopsy planning, tissue adequacy, and coordination across the care team can influence biomarker testing and treatment planning. The discussion emphasizes practical strategies to support current and future molecular testing needs. 

Transcript

Kelly Conger: Hello and welcome to the Oncology Learning Network. I’m Kelly Conger, and on today’s episode we’ll be discussing tissue acquisition and biomarker testing in non-small cell lung cancer. Our guest today is Dr Jamie Chaft.   

Dr Chaft: Hi, I'm Dr Jamie Chaft, professor of thoracic oncology at Memorial Sloan Kettering Cancer Center. 

Kelly Conger: Thank you so much for joining us today, Dr Chaft. Can you start us off by describing why the initial biopsy is so crucial for newly diagnosed or suspected lung cancer patients? What is it that makes this first step so important?  

Dr Chaft: The initial diagnostic biopsy in non-small cell lung cancer is key to opening up therapeutic opportunities for the patient in the room. There is nothing that can be wasted on that initial biopsy, and everything must be done. Unfortunately, everything seems to become more and more with every new data set we see, and drug approved. So, understanding how to triage material, what is absolutely essential now versus what can wait for testing later. And how long you have to wait for these results until starting therapy are all challenges we face every day. So first of all, we need a histologic diagnosis. So that material must be used to diagnose non-small cell lung cancer versus small cell or metastatic disease. And if non-small cell, we need to know if it is squamous cell carcinoma or non-squamous non-small cell lung cancer. And while biomarker testing is necessary in each, the degree to which we push for testing results in non-squamous, non-small cell lung cancer is with greater priority. 

Kelly Conger: So once the histologic diagnosis is made, what else can a biopsy tell clinicians? And what sort of work-up goes into determining next steps?  

Dr Chaft: So beyond the histologic diagnosis, the first and foremost biomarker is PD-L1 expression by immunohistochemistry. This really helps us direct frontline therapy when there is not a targeted therapy option. In terms of targeted therapies, we take a two-pronged approach to biomarker testing, at least for patients with metastatic disease. So for patients with metastatic disease, there are many publications demonstrating the clinical utility of parallel, contemporaneous liquid and tissue testing. Now, liquid biopsies cannot be relied upon in the early-stage setting due to issues with sensitivity. They are generally quite good with advanced disease, particularly if there's a high disease burden. If the liquid biopsy is negative, it is essential to wait for the tumor biopsy. Now, what do we do with the tumor biopsy? The real answer today, based on the NCCN guidelines, is comprehensive next-generation sequencing, along with, if there is material, immunohistochemistry for expression of MET and HER2. Now, what does comprehensive biomarker testing entail? In an ideal world, that is both DNA sequencing and if DNA does not show you what you're looking for, RNA sequencing, which is far more sensitive for picking up alterations or specifically gene fusions in ALK, RET, ENTREC, and ROS, as well as better at MET exon 14 splice variants.   

Kelly Conger: So that initial biopsy really needs to have enough tumor tissue to support this array of biomarker tests. But what happens when there isn’t enough tissue? And how do you, as a clinician, guide choices around whether to re-biopsy or to start or hold treatment?  

Dr Chaft: Tissue insufficiency and delayed biomarker results are clinically relevant struggles we face every day, and it really depends on two factors: how sick is the patient in the room, can they wait for a repeat biopsy, or do you need to start therapy immediately? And what is your pretest probability of finding one of these beautiful, actionable oncogenes? If that therapy you anticipate giving can cause harm after immunotherapy, it's not uncommon for us to start with a cycle of chemotherapy and hold the immunotherapy while repeating testing. If the liquid biopsy is negative and the tissue is insufficient, you have to think about the patient in the room. And if they are a light smoker or never smoker, if they are young, if it's adenocarcinoma histology, we do our best, if the risk is acceptable, to obtain a second tissue biopsy for comprehensive genomic testing. It's really our job to open up the door of therapeutic opportunities to our patients. And if that initial biopsy is inadequate, a second one is indicated.   

Kelly Conger: The biopsy and subsequent biomarker testing seems to really allow for a personalized approach, but I know this can be a complicated and multifaceted process. I’ve heard the term ‘tissue stewardship’ used to describe this sort of thoughtful management of biopsy material. Could you elaborate on your experience with this and best practices for our listeners?  

Dr Chaft: Tissue stewardship is a buzzword in thoracic oncology. And unfortunately, as a clinician, you often feel like you can't influence that process. I think communication is key to tissue stewardship, both from prior to the biopsy to when it hits the lab. For example, if a patient's undergoing a bone biopsy, letting the interventionalist know you need that to not be decalcified so that you can utilize it for molecular testing needs to be done ahead of time so they can make a note for the pathologist. If the tissue biopsy is going straight to the pathology lab, letting that pathologist know the patient's a never-smoker may eliminate extensive immunohistochemical tests. Really in a guideline-based fashion, the pathologist, if they suspect non-small cell lung cancer, should be performing IHC for P40, which would suggest squamous cell carcinoma, or TTF1 for adenocarcinoma, and nothing else unless they really aren't sure where it came from. For the pathologist to know, I suspect, a lung cancer, it really helps them triage their battery of IHC assays and save that precious material for genomic testing. 

Kelly Conger: Dr Chaft, thank you so much for sharing your insights with us. Today we’ve covered the important role that the initial biopsy plays in non-small cell lung cancer, relevant biomarkers and how to test for them, and how to navigate tissue insufficiency and tissue stewardship. Thank you to our listeners for tuning into this segment on the Oncology Learning Network.