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Welcome to the Quick Consult podcast, brought to you by Metall. Before starting this podcast, please review the faculty information, disclosure statements, and learning objectives using the link in the episode description. To claim your CME credit, complete the evaluation using the link in the episode description. This podcast is a continuing education activity managed and accredited by Current Concepts Institute in collaboration with Metal. This activity is supported by an independent medical education grant from Pfizer. Welcome back to the final episode of First Line Focused Perspectives, and in this series, Biomarkers in action, we're going to be talking about high precision oncology hinges on timely and accurate biomarker testing. Yet real world practice is often inconsistent. Today, we'll dive into how to overcome these barriers and confidently integrate molecular results into treatment planning. We welcome back Doctor Zev Weinberg. Doctor Weinberg, let's start at the very beginning. When dealing with newly diagnosed metastatic colorectal cancer or non-small cell lung cancer, when is the optimal time to order BRAF testing and which other key biomarkers should always be ordered alongside it? Thanks. So for newly diagnosed Metastatic colon cancer, we'll start with that. I think some of the critical biomarkers to know from the beginning include MSIFI status, which can usually be determined by immunistic chemistry. That can be done quickly, often at most centers, and BRAAF. Those are the two most critical, along with, of course, KRAS, which has been along for a long time. The simplest way to get all of this done at once is certainly an NGS panel, next generation sequencing panel, which can be done from many, many vendors that should turn around the basics KRAS, BRAF, MSIH certainly if it's not available by immunistic chemistry and give you sort of the main critical elements that you need to get diagnosed, to assign appropriate therapy from the beginning. Those are the main three biomarkers and Colorectal cancer, non-small cell lung cancer, there are so many, of course you need to know EGFR, AC, and a host of others. So in that context, almost every pathology center has a basic biomarker testing platform that checks all of these things, including PDL-1 and ALC EGFR, you name it. So it's good to get BRAF with all the other stuff. Tissue biopsy remains a gold standard, but liquid biopsy or circulating tumor DNA analysis is. Increasingly useful. In what clinical scenarios, particularly in the community setting, should a healthcare professional utilize liquid biopsy to ensure a timely result, and how reliable are these methods for identifying the BRAF V600E mutation? So I mean the practical answer is when there's not adequate tissue available or when there is a paucity of tissue, for example, if you have a fine needle aspirate. Or you can't find the tissue, it's done in another hospital. Liquid biopsy has the potential to turn us around sometimes within 5 to 7 days. So that's really fast and, and, and, you know, faster often than tissue. It is quite concordant with tissue when it comes to the most actionable mutational panel, which includes BRAF in many contexts. So I do think the Majority, and it really depends on the individual company providers or vendors, but the majority of them are quite sensitive and specific when it comes to picking up a mutation of BRAFV 600. Interpreting the full molecular report can be daunting. What practical advice do you have for community oncologists to quickly translate? A complex panel of results, especially when commutations are present, into a confident first line treatment choice, ensuring the BRAFV 600E status is acknowledged and prioritized. So most of the vendors have done a better job now of putting up front on the top page, what are the critical elements, and those include Uh, you know, for example, in colorectal cancer, MSI high, KRAS, BRAF, and they put that on the top. So you're, it's, it's, it's important to point that out. And often there's an assignment of, you know, what would be considered a standard therapy. In lung cancer, of course, there's so many more that are considered standard in the front line, so they have to spend a little time going through it. I do think that, you know, because BRAAF is now immediately actionable, it should be considered one. The most important ones to look at from the get-go, that you notice it and you, you're, you're in tune with the BRAF mutation because the implications of the treatment upfront are so critical in both colon and lung. We've seen a small suggestion of benefit for checkpoint inhibitors in BRAFV 600E mutated patients who are also MSI high. Could you briefly comment on how we currently sequence or choose between a checkpoint inhibitor. And BRRAF targeted therapy in those specific co-mutant patients. Right, it's a very good question, and it is, albeit rare, it does happen in those patients certainly with the Lynch syndrome or something along those lines. And there is not yet a lot of data to combine BRAF inhibitors, EGFR inhibitors, and checkpoint inhibitors together. Some of those studies are ongoing for now. I think most people will start with a checkpoint inhibitor. Probably because it's easier in a lot of respects and has been shown to have such outstanding outcomes. Although at the moment there are several randomized trials looking at this exact combination. For now, I would say probably the majority are starting with a checkpoint inhibitor if they're truly MSA high and then considering a BRAF targeted therapy in second line. That's the subject of A number of studies ongoing at this moment. Dr. Weinberg, thank you for sharing your expertise on these complex topics and for sharing your invaluable insights in this series. We're incredibly grateful. Thank you. Thank you for joining us for the first line Focus Perspectives podcast. We hope this series has equipped you with the confidence and knowledge to better integrate the Latest evidence on biomarker testing, treatment selection, and adverse event management into your practice. To access more enduring modules, clinical summaries, and case-based question banks for this program, please visit metaleducation.com. Thanks for listening. To claim your CME credit, complete the evaluation using the link in the episode description. See you next time on the Quick Consult podcast.