Real-World Decision Points in Biomarker-Driven NSCLC Management

Dr Jamie Chaft discusses how longitudinal biomarker assessment can support treatment planning, resistance evaluation, and rebiopsy decision-making in NSCLC. Key topics include disease progression, tissue limitations, prior assay results, multidisciplinary collaboration, and individualized testing strategies. 

Transcript

Kelly Conger: Hello and welcome to the Oncology Learning Network. I’m Kelly Conger, and on today’s episode we’ll be discussing longitudinal biomarker testing strategy 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 for joining us today, Dr Chaft. To kick things off, can you tell us about what happens at disease progression for patients with non-small cell lung cancer in terms of biomarker assessment?  

Dr Chaft: So in general, in terms of oncogene driver mutations, the foundational clone, the oncogene driver, is always there. So when do we reassess biomarker landscape, both in terms of genomic and expression landscape, and it tends to be situational. So certainly for EGFR, ALK, ROS-driven non-small cell lung cancer, when the disease progresses after frontline therapy, there is sometimes a specific resistance mutation that can direct next-line therapy. Those are unique situations where we will often re-biopsy either with liquid and or tissue testing. It's also important, at least with EGFR, to assess for histologic transformation to small cell lung cancer. In terms of non-oncogene-driven lung cancer, we have FDA approvals in the second line that require MET and HER2 testing. So in that setting, if not done on the initial biopsy, and IHC is not routinely done by all companies providing NGS testing. Those can be ordered either as institutionally performed or send out tests. 

Kelly Conger: Now how do you, as the oncologist, make the decision to re-biopsy at the time of progression?  

Dr Chaft: At disease progression, your decision to reassess biomarkers is really based on your available therapies and or the patient's fitness for a clinical trial. There are many times where a fresh biopsy may drive a new therapeutic decision, particularly with acquired resistance. And there are other times where baseline diagnostic tissue didn't provide all of your biomarkers where you may consider a repeat biopsy. We're still learning about the change in overexpression and amplification over the course of a patient's cancer treatment. And if you're really out of therapeutic options or looking for a biomarker match therapy in a patient who hasn't had one, a repeat biopsy is sometimes considered. I will say that if a clinically relevant tissue-acquiring procedure is done, you can always utilize that, such as a thoracentesis or pleural fluid drainage. 

Kelly Conger: The process of obtaining the re-biopsy of course extends to other members of the care team. How should oncologists go about re-initiating this workflow and what does the team need to be aware of as the treatment strategy evolves?  

Dr Chaft: So part of being able to obtain the tissue you need for comprehensive molecular testing as well as expression data is that clear communication across the multidisciplinary team to the pulmonologist or the surgeon or the interventional radiologist, whoever's performing that diagnostic biopsy. They need to know what you need in terms of tissue for the testing. It's not just a diagnosis anymore. Now, fine needle aspirates were often thought to be inadequate for this type of testing, but they're perfectly sufficient as long as enough cells are acquired. This also comes up when you have a patient who presents with an effusion, whether it's pleural or pericardial. Be sure to, in advance, request all of the fluids sent to the path lab and for the pathologist to make a cell block so you can do this diagnostic testing in the most comprehensive way possible to open up treatment options for your patient. 

Kelly Conger: What can you tell us about the future of biomarker testing and tissue stewardship, particularly as it applies to the longitudinal strategy for non-small cell lung cancer patients?  

Dr Chaft: What's interesting out of ASCO this year is that comprehensive biomarker testing has now moved to the earliest stages of lung cancer. So diagnostic tissue stewardship is more important now than it ever was because we're talking about curing patients. So whereas historically we've tested initial diagnostic biopsies even in the early stage for PD-L1, ALK, and EGFR, we now need RET fusion testing, which is most optimally done with an RNA-based methodology. So from initial biopsy, we need comprehensive molecular testing and PD-L1 expression. Now, if that patient relapses, additional therapeutic opportunities are opened up by adding immunohistochemistry for HER2 and MET and looking at overexpression. So preserving that tissue from diagnosis on is essential, but you need to make sure you have all of your biomarkers. And I would argue we don't save tissue for a clinical trial enrollment or to test it later. We use what we have to get all of the information we need as soon as possible. 

Kelly Conger: Dr Chaft, thank you so much for your time today. We have discussed how to address biomarker testing at treatment progression, including multidisciplinary collaboration and the latest updates out of this year’s ASCO meeting. Thank you for listening to this segment of the Oncology Learning Network.