Lung Cancer ESMO 2025 Highlights: MDT-BRIDGE, FLAURA2, SOHO-01, Beamion LUNG-1

Multidisciplinary Approach in Resectable NSCLC: MDT-BRIDGE Hello and welcome back to another episode of the Oncology Brother podcast. I'm Rohit Gosain and here with my brother and Co host Rahul Gosain. Asthma 2025 just wrapped up with thousands of abstract and exciting science that was presented. Our goal today is to focus on practice, changing and informing studies from those that were presented and walk away from big take away messages from the world of lung cancer. We are very excited to be joined by a friend, mentor and leader in thoracic medical oncology, Dr. Rami Manoshakian from the Mayo Clinic. Rami, thanks so much for joining us, Sir. Speaker 2 Thank you so much for having me. Then once again, I always like to start by giving you kudos on what you do. It's just amazing the education platform that you are on to help many oncologist out there take better care of patients. So congratulations. Speaker 3 Rami, welcome and as always, thank you so much for your kind words. OK, so for everyone listening over the next few minutes, we'll touch on MDT bridge trial in early non small cell lung cancer, then switch gears to Flora 2 update for EGFR positive disease and then close off with her 2 positive non small cell lung cancer. Primary. Can we start off with MDT bridge trial? This is in borderline resectable non small cell lung cancer in these settings or options are a new adjuvant approach with Checkmate 816 which is nivolumab and chemotherapy or periop and post op approach based off multiple studies or Pacific trial. If this is truly unresectable, can you walk us through this study and its findings? Speaker 2 Yeah, absolutely. Thank you so much for bringing this study among many amazing studies reported in MO 2025. So this was a global phase two studies. I really, really like the the the concept here. As you mentioned, there's so much happening in this field of neoadjuvant period up for those resectable locally advanced, you know, patient to a non small cell lung cancer. We know is the you know, jury still out on the neoadjuvant only versus the period of that's the whole talk and an ongoing debate for what I like in this study is testing the concept of a heart stop multi disciplinary assessment throughout the process. Reminder for all of us to do better for our patients by making sure we're always reassessing where they are in the treatment journey. It was, you know, a study that basically, you know, try to label patient as whether they are resectable stage 2B to 3B versus borderline resectable. And we encounter this in our clinic every day, you know, giving them basically a chemo, IO in particular platinum based, you know, with IO for two cycles, volumab in particular for two cycles, then reassess where they are and see are they still deemed potentially resectable versus, you know, maybe not especially among the ones who were initially they were reported, maybe borderline. If they deem resectable, go ahead and give one to two more cycles, you know, to complete total of 3 to 4 adjuvant. If you want a given one every three weeks, then go to surgery or if they were, you know, deemed by the evaluation that those cannot be irresectable, then proceed with the, you know, concurrent chemo radiation therapy. So kind of like that concept, you know, for us as opposed to the, you know, just give everything up front. The three cycles or the four cycle that were we used to seeing where we are was very helpful. What what we're seeing here, what I think is fairly impressive result. I mean, first of all, you know, majority of the patients, I think overall the resected ones were about like 85%. And the other numbers that I like to see, so that the primary endpoint was resection, you know, was were these resected or not among the one who were deemed resectable overall later on 95%, you know, after the first assessment were deemed that they're still resectable. And among the borderline resected resectable upfront about 82% were felt to be resectable and not everyone ended up getting, you know, resection. I think, you know, reading the numbers overall finally was the 92% of the overall resectable got resected and about 71% of the borderline got resected. This is excellent numbers to tell us that a large percentage of patients could undergo surgery. Many of us out there believe that surgery yields some excellent outcome for these patients in order for them not to be able to get concurrent chemo radiation. So All in all, good design, good concept. I like what we're seeing. Speaker 1 Thanks so much for breaking down that Rami. With regards to what this study shows is the importance of multidisciplinary in all stages of non small cell lung cancer. As you stated surgical resection is extremely important and if one is not able to go for that, well that's where radiation fits. And what we are seeing is again as you stated with the periop studies, what we also at asthma was the overall survival from Keynote 671 where at five years which was an update which we were seeing about 65% of these patients do well with pembrolizumab therapy, which looks rather similar to what we have seen with neoadjuvant treatment. And of course, not to forget NGS testing where we do have patients who have common EGFR mutation, one should utilize osemertinib and adjuvant setting and also if ALK positive then relying on electinib. FLAURA2 Update: Osimertinib Combinations for EGFR+ NSCLC All right, moving along, great segue to focus on our next study which is Flora 2. Here we have chemo plus osimertnib versus osimertnib in common EGFR mutations in frontline settings. We had seen initial data of this at world's lung and now what we are seeing here is more oral survival in different subsets from your thoughts particularly this concern of CNS disease because this is rather common in non small cell in metastatic space. Speaker 2 Yes, absolutely. Another landmark important study is we know we got some of it on during the ward lung 2025 and now some more updates. You know patient with advanced non small cell lung cancer with EGFR mutation in particular the most common Exxon 19 or LT58 RI mean the last couple of years give or take right. We've been having these ongoing debates with a lot of new options for these patients especially the combination also Martinet has been the standard of care for quite some time with excellent outcomes. But we do know that good number of patients at some point you know their disease become you know resistance and their cancer progress. So the so so-called combination, you know, therapy upfront is, is what is being now talked about. We have the Amivantanap Losartan, another whole option that is excellent option also that needs to be offered for patients with excellent overall survival data discussing toxicity and so forth, which is a big topic. And here we go. We have the flora too that is testing Osimertanap plus chemotherapy, carboplatin or cisplatin with amitrexate, the most common regimen used in, you know, patient with stage 4 adenocarcinoma. Impressive result. We've known that we've seen initially the progression free survival a while ago we were all anxiously waiting for overall survival data and you know, at least to say definitely impressive result showing, you know, significant, clinically meaningful and statistically significant improvement in overall survival. It has a ratio of 0.77 with a median overall survival improvement of about 10 months, seeing the OC plus chemo reaching a median of four years. We all need to take a moment here to ask whether with this data, whether with the Mariposa of an event of Blazortanet to to feel so good about this, you know, number of patients who are now able to survive multiple years on this combination of treatment. Most importantly in the updates here, of course the subset analysis, you know where is this combination needs to be considered, where is it showing the most benefit? The patient with high risk features or more aggressive disease, CNS metastasis. Look at these outcomes where these patients are doing better on the combination. Patient with liver metastasis, patient with ATP 53 Co mutation, patient with circulating DNA showing EGFR mutations. This is definitely in my opinion a standard of care option that we owe it to our patient to discuss it, discuss the Mariposa regimen and discuss for submertinib as a single agent also as a potential option keeping in mind patient, you know, including patient and the decision making, but also present the data to them and help them and guide them, you know, make a decision especially in those high risk features. And last thing I would mention is also that, you know, overall the toxicity profile was what we were expecting. I don't like to use the word manageable or acceptable because some patients may really get a hard time or have issues with the toxicity. But it is what we're expecting with optimizing toxicity management, we are able to help some patients. And last but not least, good number of patient did not need to be on a chemotherapy, the maintenance chemotrex it for a long term something to keep in the back of our mind. Speaker 3 Absolutely. These are exciting times. Again, because of this, our patients are living longer. So just to recap in this space, we now have two potential combinations, amivantamab with lizertinib and chemo with osmertinib. And this is what we're seeing with the updated overall survival. And on our end, we've recently covered the space with Doctor Eric Singhy in our challenging cases. So before I move on from this topic, another study, North Star was a phase two study presented at ESMO where we saw that adding local consolidation therapy showed improved overall survival in the same patient, EG for mutated disease. I would like to believe, Rami, that a lot of us are already doing this today in our practice, but now we have more data to support this practice. Speaker 2 Yeah, I'm so glad you mentioned it. I think it was another important study that validated to your point what we're already doing. Local therapy is very important. We have, you know, different, you know, research, a lot of, you know, scientific rationales. Why it would be helpful to consider for patients with not just oligomerastatic disease, but even some patients who have actually multiple or you know, polymerastatic is to consider some local therapy, whether radiation or surgery to add to the effect of the systemic therapy. We've seen significant improvement in medium progression free survival. I think it was about 17 versus 25 months. Looking at these, you know, number of patients wherever they got some percentage got surgery, radiation or both, no major adverse event or a new adverse event. I think it's something we need to consider on a case by case for every patient. And I'm not talking about the oligo progression, which we all know we're talking up front. Many of us believe to maximize outcomes and survival, including some local therapy is the way to go, not just in this particular, you know, patients EGFR, even in other lung cancer or even other cancer to keep a local therapy as an option. Speaker 3 To be offered absolutely and rohed. There was a reason you mentioned that multi D is important every stage. This is yet another example. Speaker 1 Because these manage these interventions are rather leading to increase survival. Speaker 3 Absolutely. All right. SOHO-01 and Beamion LUNG-1: HER2-Positive NSCLC Advances Now let's pivot to our her two mutated non small cell lung cancer, which is often reported as ERB 2 mutation on our NGS. We initially had TDXD here and then Song Gertaneb recently approved. We'll likely see Seva Bertineb approved here as well based off Soho 01 study. Rami Soho 1 update was presented at ESMO. Can you touch on this study and its findings? Speaker 2 Absolutely what an era we're living in for patients with lung cancer, particularly non small cell lung cancer is, you know, again, take a moment to echo what what you guys already mentioned also at the beginning, the reminder for us of the importance of NGS testing. I know here we are probably, you know, preaching the choir, but there's still some patients out there that they're not getting the full testing. So let's always keep helping these patient out there spread the word. Every patient with advanced lung cancer, non small cell lung cancer, especially carcinoma, next gene sequencing testing. So we can pick up some of the common mutation and some of this mutation that might be more rare. You know her to not necessarily a mutation that you're going to see every day in clinic, but there are some patient that you're seeing today or tomorrow in clinic that they're going to have it and get cancer and we need to pick it up. Historically, we didn't have much for this particular mutations. And then like you mentioned the TDXB approved in the second line when with the first line, we use some typical, you know, eye for chemo IO, although we don't believe that IO may work a lot in those patients, although in some patient there might be. So we had this study is looking another oral TKI, you know, that is overall, you know, I would say again, if tolerability is very important, especially with TDXD, we know there is some toxicity issues. I would like here to say that it's a tolerability that I like to call it a favorable in general. Again, we understand some patients unfortunately may get some major side effects and this is looking at this oral therapy in you know different cohorts for patient with her two mutations. Again impressive efficacy outcomes. This looked at cohort of patients who are treatment naive who did not receive any treatment response rate about 7072%. Looking at patient with retreated but they did not receive a prior her two you know drugs again response rate in the 6065% and then the one who were pretreated with another her two were still seeing some good response about 38 to 40%. And in all these cohorts, another good patient population with a clinical benefit rate, which in my opinion is also important. Grade 3 or above adverse event, event about 3032%. So, you know, historically that's not too bad. We know the diarrhea here is something to notice, you know, more compared to other drugs. But All in all, like discontinuation rate was very low, I believe around 2 to 3%. I think this is an effective drug. This is a drug that seems with acceptable tolerability profiles. I think this drug is going to play a role when approved in treatment of such patients. Speaker 1 Indeed, Remy, I want to reiterate the point about NGS testing. 1 needs to do that upfront, but also to catch some of the resistant mutations on progression of the disease. Another TKI in space here, which is an oral regimen with favorable side effect profile, especially when you're comparing that with TDXD, which has almost like a chemotherapeutic side effects like fatigue, alopecia and not forgetting about ILD. Rahul, I agree, this will likely get approved soon. Remy, can you touch on our last here, that is Beamy and Lung One as this is what led to the approval of Zone Gertneb. What we would like to know is if all these are available, that is Seva, Bertneb, Gertneb and now of course TDXD, How are you sequencing them? Speaker 2 Yeah, absolutely. I mean great questions and this is again another ongoing debate. The good problem to have, I think you know we're heading soon to the era where you know her two drug is going to be used in the first time. We hope more larger studies continue to validate and ultimately we get potential FDA approval with this impressive data that we've seen with Soho 01 and now the beanie on lung one. This is a good segue about zongertinib, which is a drug currently approved after progression on chemotherapy in particular. Some of us already using it before the TDXD. And honestly I can tell you right now, especially as of the last few months, it's becoming my preferred agent to use in the second line after potential first line IO or chemo IO majority. This study here the Binyong 1 is testing is giving us the result of cohort to where it was the first line, you know given first line, which I think it should be again another oral TKI and response rate, you know with 77%. I mean, this is amazing. Even when we look at all targeted therapy, the Disease Control rate in the high 90%, This Is Us saying every patient benefiting of this drug, the overall the toxicity profile, I would say a favorable. I mean, again, we can't compare studies with each other, but relatively speaking, those of us, whether we're under trial or started using it in practice, we can attest to that. That doesn't take away that we always should do everything we could to to address all the symptoms, quality of life. Every patient sometimes maybe in a minor side effect could turn their life, you know, 'cause major issues. The study also reported six months, I think duration of response about 80%. So this is a durable response for and then the progression free survival again, six months median or six months I should say about 80 percent, 79%. It's just another very effective drug that we think patient would be able to tolerate. And this drug already approved in the second line. I think this drug could be used in the first line leading to your Excel question. I often re keep repeating the same sense. It's a good problem to have. How are we going to sequence them right now? I've been in touch with colleagues and some companies to try to see, you know, how do we be how do these drug do after each other? Is there any data? Are we going to get any more data? I see myself sequencing some her two drugs and not necessarily going into chemo, chemo IO, maybe later lines. There are more potentially coming in the pipelines or such a rare mutation. If I look at the two studies, it seems like Zongertonet and the Siva Burtonette both in the first line have very close efficacy data. You know discuss based on talk, based on on patient factors, the potential profile, other factors, Would I sequence them one after the other? Would I use a TDXD possibly, Could I use the three of them? I think this is going to be an ongoing discussion as long as we declare to the patient that some of these sequencing, we don't have great data exactly to look at it, but we think that her two potentially could be more like the ALK where you know one her 2 after drug after another could still work. I do recommend potentially rechecking the NGS you know, ensuring there is no new resistant mutation, no transformation, no other things to do when you're treating such. Speaker 3 Patients, you know, right now we're stuck with cross trial comparisons, but when we're putting these two studies side by side, that response rate and CNS activity by these oral Tkis is very impressive in frontline and in refractive disease. And a few things that were brought up, you have to keep side effects in mind. But the oral Tkis, sevepratinib or azungurtinib, rash, diarrhea, fatigue, whereas with TDXD which is IV, you have to keep ILD, fatigue, nausea and alopecia in mind. ESMO 2025 Lung Cancer: Key Takeaways and Outlook Rami, we've covered a lot here, but before we wrap, any final thoughts around ESMO or another study that caught your attention. Speaker 2 I'm actually going to use one of the things you mentioned about my final thoughts, the CNS activity in these drugs and a lot of these other drugs that we're seeing. You know, today we discussed 2 targeted therapy for her to the flora too. And we're seeing these sicker patients, patients who have more morbid disease CNS, which has always been the, you know, the ones that are that are, you know, that hard to manage and they don't respond well to systemic therapy. We're living in an era to see now a lot of other, you know, new targeted therapy or different combinations are able to reach and to attack these cancers and metastasis in the toughest area, especially in the CNS. We have some data in the laptop and Angel, so I'm excited. Meetings like ESMOS 2025 and other great meetings are where some practice changing, you know, or informing trials are being presented remind us that we why we have a long way to go, but we also have made so much progress in the fight against lung cancers. There's a lot of other studies were presented, a lot of talk about the HARMONY trial, HARMONY 6 trial in a in a squamous cell carcinoma, another area of unmet needs, which created a lot of buzz, a lot of debates. We know this trial done mainly in a part of the world in China. We have to be open to validating trials. We like to see the concept of this by specific VEGF and PDPDL 1. You know, to see a drug to have such efficacy is, is exciting. Waiting for more data to come, but it's only the beginning. The last 5-10 years we have seen just a plethora of the study of exciting things with ultimately all great role to help these unfortunate patients. There is no better time to be an oncologist, I'm sure you agree. Speaker 1 Absolutely, indeed. I mean these are exciting times as they're oncologists as well as patients and their families where we are seeing about close to 40 new drug approvals each year in the hematology oncology space. And we saw what you stated, very exciting ADC's and vice specific here at ESMO in lung cancer space. And but what you stated though they were in China, but they are telling us that the science is effective. So we need to have a broader or global audience being involved here and we'll have to wait for the mature data as well. Rami, thank you so much for taking the time to go through these important studies that were presented at ESMO from lung Cancer Space for our listeners. Let us go or a quick recap. Speaker 3 In this discussion with Doctor Rami Manushakian from Mayo Clinic, we focused on lung cancer abstracts from ESMO 2025. MDT Bridge study stood out as it provides a little more guidance on what to do with their borderline resectable non small cell lung cancer patients. It continues to reiterate the importance of multi D approach. Then we touched on FLORA 2 which confirmed overall survival benefit from olzomertinib with chemotherapy in almost all subsets for our EGFR mutated disease, keeping our combination options of amivantamab and lizertinib or OC with chemotherapy in the settings as important. Speaker 1 To close, we covered our HER 2 positive non small cell lung cancer space where we currently have Zolngartineb and TDXT available, but very likely we will see several Bertineb in this space as well given phenomenal overall response rate and its favorable side effect profile. Thank you all for tuning in. Be sure to check out more of our episodes from practice changing updates, new approvals and major conference highlights. We are the oncology brothers.