ASCO 2026 Head & Neck AND Sarcoma Highlights – Drs. Samantha Armstrong & Ari Rosenberg

Hello and welcome back to the oncology brothers podcast. I'm Rahul Gossein here with my brother and co-host, while it goes saying, today we're diving into your conference highlights from ASCO 2020-6. A lot of data was presented here. And in this discussion, we're focusing on head and neck cancer and sarcoma studies. For this, we're excited to have Dr. Ari Rosenberg from University of Chicago focusing on head and neck cancer. And we also have one half of the two-ong docs, Dr. Sam Armstrong from Indiana University, focusing on sarcoma. Ari and Sam, thank you so much for joining us. Ari and Sam, welcome. We want to touch on two studies from head and neck space and then two in sarcoma space, starting out with head and neck. Sam, I'll keep these questions for Ari, but feel free to chime in if you have any suggestions. Ari, first study we have is abstract 6.004. That's focusing on nasopharyngeal carcinoma. Though rare entity in the United States, but hoping can we extrapolate what we learn here to other head and neck cancers. This is a phase three study where we are looking at carboplatin versus cisplatin in induction and concurrent chemoreadiation therapy for locally advanced nasopharyngeal carcinoma. In our clinic, we are often debating the high dose cisplatin versus weekly cisplatin and then we reserve carboplatin for cis ineligible patients. Ari, what did the studies show and importantly? Can we extrapolate these findings to other head and neck cancers? This is a study that was conducted in East Asia, which is an area where nasopharynx cancer is endemic and we see huge numbers of local regionally advanced nasopharynx cancer patients, whereas in the U.S., that's actually a relatively rare disease. And just to set this, unlike many types of head and neck cancer, for whom definitive chemoreadiation is really the paradigm and induction remains an unproven paradigm. Inelfarax cancer is actually different. This is actually a disease and where we have level one evidence for the incorporation of induction chemotherapy followed by concurrent chemoreadiation. There's also quite a bit of data for adjuvant chemotherapy as well. And so this is actually an area where induction chemotherapy is a very standard approach, which is different than many of the other more common types of head and neck squamous cell carcinoma that we see in the United States. Importantly, just to point out here is that the induction regimen selected is an induction regimen we often use when we need to use induction chemotherapy for local regionally advanced head and neck squamous cell carcinoma patients that we see in the U.S. that require induction chemotherapy either because they have very symptomatic disease, high burden of disease, we need rapid debulking. But actually in nasopharynx cancer in the U.S., at least most of the induction chemotherapy patients receive a gem sis, so gem side of being with cisplatin as the induction. That's the New England Journal paper for a number of years ago that established that as really the standard of choice for nasopharynx cancer patients, particularly EBV Associated Nasopharynx Cancer patients. So I'm just going to start with that caveat. That being said, this is also a disease that's very responsive to platinum taxing. And this was a very interesting study that tried to look and see could you simply replace this platinum with carboplatin during both the induction phase and the concurrent phase and see if it hits the non-inferiority. As you talked about, the primary outcome is failure-free survival. And indeed, the failure-free survival overall looked quite similar in the two arms and didn't met the criteria for non-inferiority. The big caveat in the discussion at the meeting talked quite a bit about what non-inferiority margin is appropriate is that it clinically relevant non-inferiority margin. And a number of the studies, an 8% to 10% non-inferiority margin, is considered for many to be not adequate. But nonetheless, outcomes look quite similar across these two paradigms. So this is quite interesting. It is nice to see carboplatin and cisplatin compared in this type of randomized design, even if it's for a disease that we don't necessarily see very much of within the US. I think in terms of extrapolating, we have to be a little bit cautious about that. I think that the high-level evidence we have for the head and neck squamous cell biology that we see in the US remains cisplatin as the standard. And that still remains the case. However, I think it does provide confidence that in cases in the US and the patients that we see in the clinic that may be cisineligible, either because of some degree of renal dysfunction or because of some degree of baseline hearing dysfunction or some degree of neuropathy. I do think that this provides some additional confidence that we can feel comfortable with recommending carboplatin-based induction and/or concurrent during that phase. I will say during the concurrent phase, there is data with carboplatin-packletaxle, which is oftentimes what I use for many of the head and neck cancer cisplatin-allegal patients that we see in the clinic. And so I think it does provide some confidence in that regard. It is the way that I would apply it to the patients that we see. This debate around cisplatin and carboplatin has been going on forever and not just in head and neck cancer, but even in other disease sites, lung cancer, even bladder cancer. And we continue to see stronger data with cisplatin. But in real life, some of our patients don't tolerate cisplatin, maybe carboplatin, is an okay choice there. But as if now cisplatin still remains the standard of care. All right, now onto another head and neck cancer study. There was a lot of buzz around origami four, where we were looking at amoevantumab in refractory head and neck cancer. Amoevantumab on our end is already approved for EGFR positive lung cancer. So to set the stage, amoevantumab is a by-specific binding to EGFR and met. And it happens to be that EGFR and met is highly expressive head and neck cancer. Are you here? What did we see and what can we learn from this study? So this was a very exciting study at the meeting. And amoevantumab has been of interest in head and neck cancer, actually, for some time, based on the fact that met in addition to EGFR is also overexpress in head and neck cancer. And it's thought to represent an important mechanism of resistance to EGFR inhibitors, like cituxamab, which is the one that we've been using for some time in clinic. And the benchmark for cituxamab in the post-immunotherapy era for HPV unrelated head and neck cancer is 24%. And so this study looked at a very large monotherapy cohort, cohort one of the origami force study, which was patients with recurrent metastatic HPV unrelated head and neck squamous cell carcinoma, who'd already progressed on prior PD1 or PDL1 inhibitor, as well as platinum-based chemotherapy, very heavily pre-treated Asian population. And the objective response rate was actually 42% in terms of the central review. It was actually 47% with the investigator-assessed objective response rate. And this is a very impressive objective response rate. Fleet response is in 15% of patients. This is really amazing efficacy data in this setting for a very heavily pre-treated Asian population. Additionally, as you show here, median PFAS 6.8 months, median OS 12.5 months in this refractory head neck cancer population, very, very good outcomes. I'll just say that we also presented at the meeting real world evidence data of patients previously progressed on platinum IO in a real world data set. And in the HPV unrelated head and neck cancer population, that median survival only around 6 months. So really an impressive single-arm study, but with a large number of patients with strong power, relatively tight confidence intervals, and head neck cancer over 90% of head neck, squamous cell carcinoma over express as EGFR met over express in about 80% regardless. We are a little bit behind our thoracic colleagues in terms of biomarker selection. I think that's something that will warrant more work. As can we figure out who the patients are that are responding best to this M-Eventa Mab strategy. There did seem to be in the forest product, particularly in the oral cavity, recurrent oral cavity patients, where the response rate did seem to be a bit deeper. These are also some of the worst biological patients that we see these oral cavity recurrent oral cavity cancer patients, nonetheless more work needed to identify the optimal biomarker fram of antimab and head neck cancer. Can I quickly jump in here? Again, when we were talking about lung cancer, we were often talking about EGFR mutated disease. That is not what we're looking here. We're just looking at that EGFR expression, but here we saw that M-Eventa Mab was working because of that overexpression. Yes, that's exactly right. I think we're learning more about understanding why cetoxamab didn't work as well as we all thought it would at the beginning, right? And it seems to be because EGFR alone is inadequate that the disease has mechanisms of resistance downstream of EGFR targeting. Before closing off on M-Eventa Mab story here, from lung cancer, what we have learned is being proactive. That is managing the rash with seramide moisturizer and a biotics like doxycycline, minor cyclin, based off of cocoon study. Also, we've seen subcutaneous formulation play out well with decrease in infusion related reaction when compared to the IV formulation. RE for lung cancer, we have utilized M-E plus LAS where we have seen increased risk for VTE. However, that has gone down with prophylactic anticoagulation. Can you touch on few side effects that we should keep on our radar and importantly, clinical pearls around that? I think the one important point that you to two is that in the head next studies we actually are exclusively using the subcutaneous formulation. So our concerns about infusion reaction really go to almost nothing. That seems to be very uncommon with subcutaneous administration. And so the dynamics of the toxicity are different in our head nut cancer population in that regard. That being said, there is no free lunch like you alluded to. This is a drug with toxicities that need proactive management in terms of the skin management we do employ the cocoon regimen. Importantly, this data predated the cocoon regimen. But now in our practice and in this study we're using like you talked about antibiotic like doxicyclein, steroid creams, oftentimes desanide for the face and all the times clavitasol for the rash on chest and back areas. Thinking about accident, rinses for nail toxicity. Thinking about keto connozzol, shampoo and other types of shampoo for scalp toxicity. These are all very important components. And importantly in head neck, unlike long, the nutritional status is particularly important. Head neck cancer patients can be nutritionally deficient, albuemmonemia and edema is a known metmediated toxicity of M/Vantamab, something that needs to be monitored very closely and optimized in these patients proactively. You bring up a very important question about VTE prophylaxis, that is something that was seen in some of the lung studies in combination with other drugs. But in head neck, these are diseases, oftentimes that have been previously irradiated, that may be very close to blood vessels within the neck that may have a propensity to bleed. And so we don't administer prophylactic anticoagulation for M/Vantamab in head neck cancer due to the particularly important bleeding risk in the absence of other indications. Absolutely. You know, at the end of the day, educating our patients and anyone involved in the team delivering this care is so important. Okay, this is a good segue to sarcoma. Because out in the community, we get exposed to one drug that gets approved in one disease and then it makes its way to another. Here we saw that M/Vantamab was in lung cancer and now on to head neck cancer. We're going to touch on sarcoma, study sarg zero four one where we're going to talk about a BEMO cyclop. This is already approved in breast cancer and now we're learning a little more about this drug in sarcoma. Sam, can you touch on this study and its findings? So thank you guys again for having me. And I was lovely to see sarcoma at the primary session. It doesn't happen often, but I was so happy to see my community represented and I think it was important for the whole oncology community to see what sarcoma is doing and how we are moving the needle forward. Despite all the setbacks and understanding, there's more than a hundred different kinds of sarcoma. So not one size fits all and we're getting better as a community to tailoring these trials down to subspecific types of sarcoma where we used to lump them together as soft tissue. Now we understand they're not the same. I think sarg zero four one did a great job of doing this because it validates CDK four as a therapeutic target for D differentiated liposarcoma amplified in more than 90% of well differentiated and D differentiated liposarcomas making it a possible target. Prior to sarg zero four one, we did do some single arm phase two looking at palbocyclic, another CDK four six inhibitor with the 12 week PFS of about 57%. And 74% in the phase two trials that we're looking at a mesyclic in this population. So now leading forward to sarg zero four one. This was the first randomized trial. It looked at 108 patients with recurrent or metastatic. So unresectable is kind of the big thing we need to realize D differentiated liposarcomas. They were randomized one to one to either a BEMA cyclib 200 milligrams orally twice a day versus placebo. They were stratified by the number of their prior lines of therapy as zero so front line or greater than one. So could have been pre-treated with say one chemo or maybe up to four chemos or maybe even immunotherapy as well. There was allowing for crossover from the placebo to a BEMA cyclib upon progression of disease. Median PFS was 9.67 months in the BEMA arm versus 1.5 months in the placebo arm so a more than a six fold improvement seen there. The overall response was 9.3% compared to zero percent. The median OS was not reached in the BEMA arm versus 25 and a half months in the placebo arm so a strong trend favoring a BEMA cyclib, though not statistically significant yet. There was post-crossed over outcomes so the median PFS at the crossover time was 3.4 months and an overall response about 4%. The median OS in that population was that 24 months. So again confirming some activity even at that crossover setting. The OS data again like I alluded to, it's immature and also that crossover design will confound the median OS analysis. The safety so there was grade three toxicity but they were similar between the arms and there was no new safety signals. The breast cancer field knows how to manage them and will be extrapolating in the sarcoma field as well and how to manage those. This is allowing for another systemic therapy and an otherwise population where systemic therapies have not proven to be slam dunks. We do have our old historic chemo's, docs, rubison, trebectidin and arypulin. Our median PFS aren't amazing in any of those so I think it's good to add on to this. I do feel that we will be using a Bemicyclub maybe monotherapy in a certain population and I think Dr. Dixon did a really good job of alluding to a trial design allowing for wide access to enroll on this trial, whether it was first line and he alluded to this in his discussion of maybe a small asymptomatic D differentiated liposarcoma hop on where you have that opportunity to try it front line or our other population where it might be more aggressive, larger, symptomatic where you might start with chemotherapy like he alluded to, but you still had the opportunity to get on the trial in a second or subsequent line. Then thirdly, it included the population where they were heavily pre-treated had been seen multiple systemic lines. They still were able to see what a Bemicyclub could do for them. I think the placebo arm, it of course raises questions as it should. I understand the pros and cons just being in the sarcoma community of why it was chosen. Really, this was to define the activity of a Bemicyclub allow access to broad patients in such a rare disease. Through the design, I want to jump on a couple of things here. Good portion of our patients did get a Bema, but again, the comparator arm was placebo. This is absolutely not what we do in our clinic. Either they'll be on chemotherapy, immunotherapy or a clinical trial at least. The dose here was 200 milligrams twice a day. For breast cancer, we are used to using 150 milligrams twice a day, but that's when we are combining it with endocrine therapy. As a single dose or rather a single drug will still be utilizing 200 milligrams BID. With regards to side effects, diarrhea, diarrhea, diarrhea. Sam, where would this drug sit in your treatment paradigm for D differentiated liposarcoma? So with the dosing, you alluded to it and Dr. Dixon did as well and that they chose the 200 twice a day based on monotherapy in the breast cancer field. He did also do a really good job of when we start talking about oral anti-cancer agents, not just these targeted CDK46 inhibitors, but I use TKI as like water and we'll talk about that in the next abstract. We do tend to in the community, start low and go slowly up. That has been something that is not done on most trials. They start high and go low, but we have seen and actually published our data here from IU on starting some of these drugs slow and push up to toxicity, finding the appropriate dose for each patient. And I do think that I would extrapolate and do the same thing for a BEMA cyclops, start low and slowly go up. The second question you asked was, where will this fall in my treatment regimens? And so I think it depends on the patient. Getting down to a very subset of sarcoma. So not only liposarcoma where there's five different kinds, but really going all the way down to D differentiated liposarcoma, excluding everybody else. And so even within that small group, there is still a lot of heterogeneity. And what we can see here is that some patients started on frontline, maybe the small asymptomatic ones, where sometimes in the real world that when we're sarcoma doctors, we do observe them. We say, hey, I'll see you in three months. It's tiny. I don't want to subject you to toxicity, knowing what we're trading off for possible marginal change. I'll see you in three months. But this could be inappropriate for those patients where maybe I will start them on that now. I think it also will be a key for my patients who are not eligible for some of our cytotoxic chemotherapy. Everyone knows, Dr. Serupisin is not a fan favorite for some people, directed in an arribulant, same thing. So the drugs will be currently have FDA approved and able to play with maybe two toxic for some, in which case the BEMA cyclop will still offer a non-keybo option for those patients. So I think it will be case by case. I wouldn't flat say I will use this as X line. And I don't think the trial was designed as such. The trial was designed looking at what is the true activity of a BEMA cyclop in this population, frontline, second line, subsequent line, sixth line. And then we as a community have to kind of decipher case by case who should be on this now and who when. And hopefully novel combinations in the future to maybe improve upon it. Sam, thanks for touching on that. Jumping onto our last study here. On just the gastro and test and all stromal tumors here, a matineeb has been the backbone. But the time of progression we have limited options here at asko 2026. We saw data on peak trial looking at what to do at the time of progression on a matineeb. Can you touch on the study? and its findings and what it means for our patients. - So again, this is the Phase III peak trial. It was presented by Dr. Wagner here at ASCO-2026. And what it was looking at is a TKI Bell Zoo Class Nib adding it to Sunit Nib. Looking at it compared to second line Sunit Nib monotherapy after progression in advance just on a mat nib. What we saw is that that combination significantly improved our PFS compared to monotherapy Sunit Nib. It had a reducing risk of progression or death by about 50%. So I do think this is very practice changing. As we know in the just community majority of just tumors are activated or are driven by the kit activating mutation. We typically think about kit X on 9 and 11 in the upfront setting, which is covered by a mat nib. But we do know that 60% of patients develop a resistance to a mat nib within the first two years. What we typically see is that there's secondary mutations in the kit. So there is ATP binding pocket mutations and those are X on 13 or 14 as well as mutations in the activating loop, which is kit X on 17 and 18. There is no proven single agent TKI that covers all of these secondary mutations. And so that is why this novel combination came about of targeting both the activating loop as well as the ATP binding pocket. And so Belzuda Clastinib is a highly selective kit inhibitor for that activating loop mutation. So X on 17 and 18. And then Sunit Nib are fan favorite for second line already approved in this setting. This covers the ATP binding pocket mutations that can emerge in X on 13 or 14. And so with this trial looked at, it was a large phase three randomized global open label trial. The population was our advanced patients with gist to progress on a mat nib. They were randomized one to one. The primary endpoint was looking at PFS. And so the medium PFS with the combination was 16 and a half months compared to 9.2 months with Sunit Nib monotherapy. The overall response was also higher with the combination at 46%, compared to 26% with the Sunit Nib monotherapy. The overall survival is immature, but I foresee us as a community being broader in covering these resistance mutations early on and also examining for them. So I do think that this could be a practice changing in the future. The side effect profiles with TKI's are all somewhat similar. Because Bell Zuclastinib is highly selective, it is safe combining with Sunit Nib without additional significant toxicities, just based on the mechanism. It's somewhat of a cleaner, more targeted TKI than some of our older TKI's that hit more targets and thus unfortunately more side effects. So I do feel it's a safe combination, but as we've seen with any TKI's, you need to be watching for diarrhea. We also need to keep an eye out for liver enzymes. So they do see an elevation with AST and ALT. This is not new to our population. We see this with many of our drugs and it's very safe, well tolerated. And we know how to manage that moving forward. Hypertension, anytime we're hitting along these VEGF pathways, more of the suitants, you need to be thinking about controlling hypertension. I know these are exciting times and I know that Rahul said this earlier, but it is good to see some of our available treatment options from other disease sites being combined here. That is Meevantumam in head and neck space from lung cancer and a BEMO cyclift for sarcoma from breast cancer space. Thank you Sam and Ari for walking us through these key studies from ASCO 2020-26 in head and neck and sarcoma space. Those tuning in, let's go over a quick recap from today's discussion. In today's discussion, we had a chance to touch on two important head and neck cancer studies and two sarcoma studies from ASCO 2020-26. We started off by discussing the data around Harboplatin being used instead of cisplatin in nasal pharyngeal cancer. And if this can be extrapolated to non-NPC disease, as cisplatin has its own fear of side effects. You know, we have to be careful before we broadly adopted this approach, as if now cisplatin remains the standard of care. Then on to our second study, we touched on Meevantumam, which is making its way in head and neck cancer based off origami for study. This is in refractory settings where we have limited options. Here we saw overall response rate with Meevantumam of 47%. And importantly, we also saw complete responses here. This is clearly an active agent here and there are ongoing trials even in frontline settings. Rohit, what did we learn for our sarcoma studies? Yes, Rahul for sarcoma. We touched on Sark 041 study, one of the plenary discussions looking at a Bemosyclib as a single agent indeed differentiated sarcoma. Here with the Bemosyclib, we saw significant PFS improvement. Though for bulky tumor or heavy tumor burden, in frontline setting, we will be relying on chemotherapy. Then to close off, we touched on peak trial, looking at Bezuklastinib with Sunitinib in just patient population after upfront imatinib. Here, the combination showed improvement in PFS of 16 months versus nine months with single agent Sunitinib. This will likely become available in near future. So look out for it. Thanks for tuning in. See you in the next episode as we continue to cover conference highlights. We are the oncology brothers.