Testing Across the Patient Journey: Longitudinal Biomarker Strategy in NSCLC

In this video, Dr Jamie Chaft discusses why biomarker testing in NSCLC should be reassessed over time as clinical questions evolve across diagnosis, treatment response, progression, and later-line decision-making. She highlights the role of prior testing history, specimen selection, and tissue stewardship in guiding longitudinal biomarker strategies. 

Transcript

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

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.  

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 enter 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.  

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. 

Jamie Chaft, MD, is an attending physician at Memorial Sloan Kettering Cancer Center, where she serves as the director of early-stage lung cancer research. She designs and leads clinical trials, striving to improve the cure rates in early-stage lung cancers. In such a capacity, she serves as study chair for the National Clinical Trials Network (NCTN) trial of adjuvant nivolumab within the ALCHEMIST program and co-lead of the Lung Cancer Research Foundation (LCRF) LEADER study bringing personalized neoadjuvant therapies to patients with resectable lung cancer. Dr Chaft's career is committed to moving drugs shown to have promise in more advanced lung cancers into the early-stage setting.