Um, I'd like to see if anybody from the audience has a question. For any of our guests today. Michael, uh, for Doctor Boger, um, we've talked about the data photo map of the Roxicca data, uh, trophy. Why does the trope 2 inhibition work in EGFR, uh, uh, lung cancer? Yeah, no, I mean, good question. I mean, certainly trope 2. Certainly, a good question. So is this on? You guys hear? There we go. Can you hear me now? Um, so a very good question. I mean, certainly with, with, uh, trope 2 is something that's pretty widely expressed across various different, uh, forms of non-small cell lung cancer, including well type, um, tumors as well. So certainly that's why it's probably been examined across really the entire non-small cell lung cancer space. But in regards to EGFR, I think we're probably at least a little bit surprised, and I certainly when these trials first started, you know, there was a lot of interest probably more in kind of the smoking induced type of lung cancers, the what. The wild type tumors and um I don't, I, you know, I did not necessarily anticipate that in the end the first FDA approval uh for this drug would be in the EGFR space but EGFR driven cancers do highly express trope 2 and in fact TRP 2 is even thought of potentially being a resistance mechanisms and may be up regulated on TKI progression and so for all those reasons it seems to be, uh, you know, I have a good amount of activity. And Nick, did you tell us that that is your go to drug now in the second line for the most part, yeah, uh, there's no right or wrong answer here. I mean, certainly, you know, docetaxel rimmierumab is also an OK option in that kind of subsequent line space, but just given. Um, just some of the challenges that we've, that we've all kind of experienced with giving docetaxel ramiserumab and, um, just some of the, you know, the, the promising data in regards to response rates as well as, uh, PFS. I know we're kind of comparing it across trials and so forth, but it does look a little bit better to me. I think perhaps there's also maybe some level of CNS penetration. I know that data is still developing in regards to data of DXT, so that, that's generally been my go to. Yeah, so let's go over the case. Um, you brought the case up. Do you wanna present it? For the, for the group, can summarize. I'm trying to think I come up with this case with the chat GPT come up with this case, but Um, a 52-year-old woman with no prior smoking history presents with a dry cough and back pain for the last 3 months. She takes daily 3-mile walks for exercise, although she admits to now having to walk slower and, and is getting short of breath. A CAT scan reveals a moderate sized left pleural effusion along with bilateral mediastinal lymphadenopathy and multiple lesions in her thoracic and lumbar vertebrae. A thoracentesis performed and uh 1 L of pleural fluid is drained with cytology showing uh adenocarcinoma of the lung. PA1 expression is assessed and shows um TPS score of 10%. NGS testing reveals an EGFR exon 19 deletion and a TP53 co-mutation. A brain MRI is performed which is negative for metastatic disease. And so the question is what would be, uh, your frontline treatment choice for this particular I'm gonna start calling on people I know, so it might be a bad thing and maybe the last time you'll come, but I'm gonna do it anyway. But I'm gonna start with our panelists. Give us your one word answer. Flora 2. Flora 2, Nick, you should have started with the audience. That's OK. I would favor Ammy Laser Amy, Amy Laser. Flora 2. Doctor Langer. Yes. So are you asking for a trial, a head to head comparison? Is that what you're asking for? And it's the only way we'll settle this. Industry ain't gonna do it. Cooperative groups, we have no idea whether the cooperative groups are gonna exist in the next 1 to 3 years. I would say here's what I Continue her manicures or manicures or not. Say that again. Continue. Continue her pedicures and manicures, and is that very important for her, you know, is, is nail beauty really important? She's a 52 year old woman, so I think that needs to be considered. Knowing what differential toxicities are posed by EGFR met co-inhibition. So what would you do since you took the microphone? Flora 2, Flora 2 is my is my go to choice, you know. We know a lot about chemo, uh, chemo toxicities. We, we, we as an institution, we manage them better, I think. So that is my preference, Doctor. Also Flora too, anybody else besides Doctor Boder, Doctor Edelman. Doctor Adam Mon right in the middle there. So you left out the, the key thing. Do you like your patient, Flora too? Do you not like your patient? Mariposa. I, I think Mariposa is horribly toxic. I think it's really an, you know, and, and there's almost no situation in which I would use that regimen. Thank you. fair Doctor Xavier, Doctor Xavier sitting there, what is your option here? For Mariposa, is the juice worth the squeeze, right? It's horribly toxic, but, you know, it's pretty impressive results. However, young woman. Uh, it would have to go for it too. I don't think you can argue it. OK, so I think we're hearing a lot about, uh, patient preferences too, right? Uh, Doctor Dampsker, the Flora to Richmond. OK, I was just gonna say I think, you know, I, I agree. I mean, clearly I voted for Flora too, but I will say in terms of the toxicity, I think you know we have to be careful about what sort of assessing Mariposa based. On the pre-cocoon days, you know, I think the toxicities were very high, but I have heard from people who've used that Mariposa with cocoon sort of really religiously that it does improve the safety profile. So I think that is worth at least kind of acknowledging that maybe over time we'll learn to do this a little bit better and it won't be toxicity-free, but better than what we saw initially, OK, um. Yeah, hi. Hi, Va Barkla from uh Cooper. Uh, I have a question. Do you, for any of you guys with the commutation with TP53, uh, change your management, change your choice here, especially if there is some hint for RB1. Uh, uh, uh, uh, commutations, yeah, no, I'm glad you brought that up, and since I was the one dissenter, uh, as far as which regimen to pick, I'll give, this will also be an opportunity to kind of further justify my choice. Now, first of all, I will say yes, there's no right, right, at least in my mind, a right answer here. I mean, I think floor 2 would be a perfectly reasonable regimen. Um, in this particular case as well. But in regards to TP53 co mutations that you bring up, that's probably part of the reason why, at least in this kind of exercise that we're having here, is that why I would probably favor Ammy Van Nebliertinib. Now, the data is still incomplete, but I know some of the Flora 2 data that's been shown, there's also been a clinical trial looking at TP53commutations combined or um chemotherapy plus osimerib combined in TP53commutations in Asia with one of their third generation TPIs. I feel like the stronger data with regards to TP 53 commutations, which I do think is a quite a bad player. I mean, we've, there's been a number of real-world analyses, um, along with analysis we've done here at Fox Chase that really does show that at least with respect to ossamer and the monotherapy, they do significantly worse when someone has a TP. 53 commutation and thus far, at least with the data that's available from both Abivan and blazertinib as compared to the Flora 2 regimen, I do think the stronger data thus far, I mean granted, it's all kind of retrospective post hoc, but the stronger data with regards to TP53 co-mutations, I think lies with Ambivan and lasertinib. And so that's part of the reason why I potentially favor that in this particular patient's case. I'd like to thank our speakers for a wonderful, uh, presentation and and and session we're gonna move on to the next session. Thank you guys.
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