Opinion
Video
Advancement in Treating Uncommon EGFR Mutations: Key Takeaways
Discover the latest insights on treating uncommon EGFR mutations, emphasizing the importance of NGS, personalized therapy, and ongoing advancements in TKIs and ADCs.
Transcript:
Charu Aggarwal, MD, MPH: Thank you all for this rich and very informative discussion. Before we conclude, I'd like to get a couple of final thoughts from each of you. I'll just go around our virtual round table here. Dr [Kaushai] Parikh, could you provide us with some closing thoughts?
Kaushal Parikh, MD: [Yes], this is an exciting space. It had been stagnant for a few years, and now it's moving [again]. I'd encourage all oncologists to consider the power of NGS [next-generation sequencing] testing upfront tissue and liquid biopsy, as well as unresistance tissue biopsy, IHC, [immunohistochemistry], and NGS testing. I think this needs to become a standard practice and not a one-off event. One more thing that I did not mention earlier, which I tend to use a lot in practice if I'm using an agent but I'm not sure about the efficacy, my practice is to get a 4-to 6-week scan. With these TKIs [tyrosine kinase inhibitors] particularly responses are quick. We've seen patients turn around in 4 or 5 days. Start your drug, get a scan in 4 to 6 weeks, and see if there is any activity, if not activities, there is no progression before you can commit the patient to a longer duration between scans.
Charu Aggarwal, MD, MPH: That's great, Dr [Martin] Dietrich.
Martin Dietrich, MD, PhD: I would echo those efforts. I think we have a great deal of new knowledge in EGFR. I think we're evolving there very, very quickly. And not only in EGFR, exon19 and 21, but we're certainly furthest ahead, but also in exon 20 in particular, a lot of excitement. I think this was a very good part. I agree with the concept of the in vivo testing. I think the level of evidence for our uncommon mutations is still relatively low. The number does not always capture all of our mutations. So getting a scan just a couple of weeks in or even using one of the MRD [minimal residual disease] technologies for assessment of a quick response, in my opinion, is a very safe way of guiding this and allowing us one opportunity to switch an agent very quickly, the responses would be expected very fast. I'm very excited that we'll be seeing additional options entering the market.
I think I mentioned the number of ADCs [antibody-drug conjugates] that are coming. I do think that we should consider not looking at these as necessarily all-comers ADCs, but that we should really try to refine which patient would benefit them. And if they have similar efficacy, then at least look at some of the adverse effect profiles as a way of staggering them, oftentimes-different targets and different payloads [that allow] us to, maybe even, sequence them. But again, the most important one is to identify these mutations and not to be afraid to ask about the results. I think they're very complex. They have multilayered analysis to them now.
I don't think anybody's expected to remember all of the binding patterns to each mutation in the EGFR space, I think there's plenty of support, through the reference labs and molecular geneticists, that is available. I think we should capitalize on that opportunity to really tailor each patient's path to the best extent possible from a molecular setting up front.
Charu Aggarwal, MD, MPH: Very well said. Dr [Nagashree] Seetharamu, if I could come to you next for your closing thoughts?
Nagashree Seetharamu, MD: We discussed quite a bit. I think we discussed that NGS is extremely important, both tissue-based as well as liquid at diagnosis and at progression. We also discussed the importance of knowing what the sites of just the progression are and if local therapies would be appropriate while continuing on TKI. We discussed afatinib as the approved option for these uncommon mutations. Most importantly, I think this is a space where a lot of work needs to be done. The first step we've already crossed, which is identifying this as an unmet need. And there's a future of exciting TKIs and ADCs that are on the horizon. For now, I think afatinib, starting with the lower dose or clinical trial, would be the best option. Amivantamab, perhaps as an off-label agent, which is EGFR mutation agnostic, and chemotherapy alone in the beginning. I would not rule out immunotherapy toward the end.
Charu Aggarwal, MD, MPH: And Dr [Tarek] Mekhail, your thoughts?
Tarek Mekhail, MD, MSc, FRCSI, FRCSEd: I actually, I would like first to thank my colleagues because I really learned a lot from this discussion today. It's inspiring the amount of enthusiasm we have. And that is reflected in what we do in the clinic. The only thing I can think of that I wanted to add is when I see a patient in these situations, it's time to think, to sit and think about what's going on. And take our time and try to understand what happened to the patient. What's the pattern of progression? Why is the patient progressing? And utilize all the data that's out there for the benefit of the patient. And there are situations where lack of evidence is not evidence of lack. You just look at what you've learned about the disease, about the pathogenesis of the disease. Do something, an in vivo testing that was used by Dr Dietrich and Dr Parikh is a nice way of saying it. We've got to utilize all our knowledge for the sake of our patients.
Charu Aggarwal, MD, MPH: Well, this has been a great discussion. Thank you again for being part of this very meaningful discussion filled with a lot of updates. Thank you to our viewing audience for joining us; we hope that you found this OncLive Peer Exchange discussion to be useful and valuable to the treatment of your patients with lung cancer. Until next time, thank you.
Transcript edited for clarity.
