Podcasts about Pembrolizumab

Play Episode Listen Later May 31, 2025 6:52

JCO Editorial Fellow Dr. Peter Li and JCO Associate Editor Dr. Andrew Ko discuss the ASCO 25 Simultaneous Publication paper "Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III Randomized LEAP-015 Study." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Peter Li: Hello, everyone, and welcome to our 2025 ASCO Annual Meeting Series where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's meeting. I'm your host, Dr. Peter Li, JCO Editorial Fellow, and I'm joined by Dr. Andrew Ko, JCO Associate Editor, to discuss the Journal of Clinical Oncology article and abstract presentation "Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III Randomized LEAP-015 Study." Now, let's start off with the relevance of this article. Andrew, can you please explain this to our listeners? Dr. Andrew Ko: Sure. Thanks, Peter. So, this was a very large international study evaluating the combination of lenvatinib and pembrolizumab. And just for context, that combination has been approved for use in other solid tumor types. It's FDA approved for renal cell carcinoma, for example, and endometrial carcinoma. But this study was looking specifically at this combination together with a chemotherapy backbone - so either FOLFOX or CAPOX - and comparing that to what at the time was a standard of care, which was just standard chemotherapy by itself. So, this very large study was intending to look at this particular novel combination. And we can get into some of the nuances of this study because the way that the experimental, the combination arm, was designed was perhaps a little bit more on the unusual side and led to maybe some imbalance in terms of how we think about the respective arms. Dr. Peter Li: Okay. We can definitely talk more about that as we go on. So, what are some of the key results of this study, and how do you think this will impact practice in the future? Dr. Andrew Ko: That's a good question. Technically, it was not a positive study. Well, it was positive in the sense that the co-primary endpoints - which included both progression-free survival and overall survival - so, progression-free survival, it did technically meet its endpoint, both in terms of the overall population and the preplanned subgroup analysis of patients who had a PD-L1 CPS of greater than or equal to 1. So, there was a PFS benefit with the experimental combination - the lenvatinib, pembrolizumab, plus chemotherapy - compared to chemotherapy alone. I will say the benefit was on the more modest side. So, if you even look at the medians, it was not a marked difference. If you look at the hazard ratios, they did meet statistical significance. On the other hand, this did not translate into a benefit for overall survival. So, when you ask, "Well, is this going to inform practice?" I'd have to say no. It highlights, I think, that JCO does want to publish articles that aren't necessarily going to be practice-changing, but that I think offer a lot of insights into trial design and important aspects of investigating novel treatments, even if they don't end up moving the needle in routine clinical practice. Dr. Peter Li: I totally agree with you. I mean, it was significant in terms of progression-free survival, but again, not clinically significant. And then overall survival, the interventional arm actually appeared to do slightly worse overall. Can you make some comments on the strengths and the weaknesses of this study, and where do you see us going from here? Dr. Andrew Ko: So, I think a couple of things worth highlighting in this study, very well designed, more than 800 patients in total. So, first of all, as I mentioned at the beginning, the combination was a little bit unique in terms of patients enrolled to the experimental arm got the combination of lenvatinib, pembrolizumab, together with chemotherapy for a very finite duration. So, that period of chemotherapy they received was only three months. And per protocol, patients then just segued to, quote unquote “maintenance treatment” with just the lenvatinib and pembrolizumab combination. Whereas patients on the control arm, meaning chemotherapy alone, would continue chemotherapy basically in perpetuity until their disease progressed or intolerable toxicity. So, there really was an imbalance in terms of, if you think that chemotherapy or continuing chemotherapy beyond that initial three-month period of time may be significant, that could have had some impact on the robustness or the efficacy of the experimental arm. There were some other aspects in terms of perhaps some differences in the rates of post-progression treatment, in other words, patients going on to receive second-line treatment. I think the other very relevant aspect, Peter, in this study was that the control arm - and no fault of the investigators - but the control arm at the time the study was ongoing just consisted of chemotherapy, FOLFOX CAPOX, by itself, without an immune checkpoint inhibitor, right? And we clearly know, based on results of several large phase III studies, and it's now in standard clinical practice, that we routinely use chemotherapy plus an immune checkpoint inhibitor. Certainly for patients with CPS PD-1/PD-L1 scores that are, well, you could argue greater than 1, or perhaps greater than 5 or 10. But the point being that the control arm of the study probably doesn't reflect what is currently used in clinical practice. And that's just always a challenge in clinical trial design, right? That when a study is designed and when it rolls out, you're always at risk in a rapidly changing and moving field that the standard of care may evolve during the lifetime of that particular trial, which is what I think you see in LEAP-015. Dr. Peter Li: Totally understand. And the survival we see from this study is also roughly similar to the combination of immuno-chemotherapy that is the standard of care today, which is, the authors mentioned, 12 to 14 months. Thank you so much, Andrew, for your input and for speaking about the JCO article "Lenvatinib Plus Pembrolizumab and Chemotherapy Versus Chemotherapy in Advanced Metastatic Gastroesophageal Adenocarcinoma: The Phase III Randomized LEAP-015 Study." Join us again for the latest simultaneous publications from the 2025 ASCO Annual Meeting. Please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of ASCO 2025. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

study journal fda leap technically annual meetings chemotherapy asco pfs clinical oncology pd l1 gastric cancer jco asco annual meeting pembrolizumab folfox peter li lenvatinib capox

Pembrolizumab and Bevacizumab for Melanoma Brain Metastases

Play Episode Listen Later May 8, 2025 23:59

Host Dr. Davide Soldato and guest Dr. Harriet Kluger discuss the JCO article "Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases." Transcript The guest on this podcast episode has no disclosures to declare. Dr. Davide Soldato Hello and welcome to JCO After Hours, the podcast where we sit down with authors from some of the latest articles published in the Journal of Clinical Oncology. I am your host, Dr. Davide Soldato, Medical Oncologist at Ospedale San Martino in Genoa, Italy. Today, we are joined by JCO author Dr. Harriet Kluger. Dr. Kluger is a professor of medicine at Yale School of Medicine, Director of the Yale SPORE in Skin Cancer, and an internationally recognized expert in immuno-oncology for melanoma and renal cell carcinoma. She leads early-phase and translational trials that pair novel immunotherapies with predictive biomarkers to personalized care. Today, Dr. Kluger and I will be discussing the article titled "Phase 2 Trial of Pembrolizumab in Combination with Bevacizumab for Untreated Melanoma Brain Metastases." In this study, Dr. Kluger and colleagues evaluated four cycles of pembrolizumab plus the anti-VEGF antibody bevacizumab followed by pembrolizumab maintenance in patients with asymptomatic non-hemorrhagic melanoma brain metastases that had not previously received PD-1 therapy. Thank you for speaking with us, Dr. Kluger. Dr. Harriet Kluger Thank you for inviting me. The pleasure is really all mine. Dr. Davide Soldato So to kick off our podcast, I just wanted to ask if you could outline a little bit the biological and clinical rationale that led you to test this type of combination for patients with untreated brain metastases from metastatic melanoma. Dr. Harriet Kluger Back in approximately 2012, patients who had untreated brain metastases were excluded from all clinical trials. So by untreated, I mean brain metastases that had not received local therapy such as surgery or radiation. The reason for it was primarily because there was this fear that big molecules wouldn't penetrate brain lesions because they can't pass the blood-brain barrier. Turns out that the blood-brain barrier within a tumor is somewhat leaky and drugs sometimes can get in there. When PD-1 inhibitors were first identified as the next blockbuster class of drugs, we decided to conduct a phase 2 clinical trial of pembrolizumab monotherapy in patients with untreated brain metastases. We actually did it also in lung cancer, and we could talk about that later on. Responses were seen. The responses in the brain and the body were similar. They were concordant in melanoma patients. Now, at approximately that time, also another study was done by the Australian group by Dr. Georgina Long, where they did a randomized trial where patients who didn't require immediate steroid therapy received either nivolumab alone or nivolumab with ipilimumab, and the combination arm was substantially superior. Subsequently, also, Bristol Myers Squibb also conducted a large phase 2 multicenter trial of ipilimumab and nivolumab in patients with untreated brain metastases. And there, once again, they saw that the responses in the brain were similar to the responses in the body. Now, somewhere along the line there, we completed our anti-PD-1 monotherapy trial. And when we looked at our data, we still didn't have the data on ipilimumab and nivolumab. And our question was, “Well, how can we do better?” Just as we're always trying to do better. We saw two really big problems. One was that patients had a lot of perilesional edema. And the other one was that we were struggling with radiation necrosis in lesions that were previously Gamma Knifed. The instance of radiation necrosis was in excess of 30%. So the rationale behind this study was that if we added bevacizumab, maybe we could treat those patients who had some edema, not requiring steroids, but potentially get them on study, get that PD-1 inhibitor going, and also prevent subsequent radiation necrosis. And that was the main rationale behind the study. We had also done some preclinical work in mouse models of melanoma brain metastases and in an in vitro blood-brain barrier model where we showed that bevacizumab, or anti-VEGF, really tightens up those leaky basement membranes and therefore would be very likely to decrease the edema. Dr. Davide Soldato Thank you very much for putting in context the combination. So this was a phase 2 trial, and you included patients who had at least one lesion, and you wanted lesions that were behind 5 and 20 millimeters. Patients could be included also if the brain metastasis was higher in dimension than 20 millimeters, but it had to be treated, and it was then excluded from the evaluation of the primary objective of the trial. So regarding, a little bit, these characteristics, do you think that this is very similar to what we see in clinical practice? And what does this mean in terms of applicability of these results in clinical practice? Dr. Harriet Kluger So that's an excellent question. The brain metastasis clinical research field has somewhat been struggling with this issue of inclusion/exclusion criteria. When we started this, we showed pretty clearly that 5 to 10 millimeter lesions, which are below the RECIST criteria for inclusion, are measurable if you use MRIs with slices that are 1 to 2 millimeters. Most institutions in the United States do use these high-resolution MRIs. I don't know how applicable that is on a worldwide scale, but we certainly lowered the threshold for inclusion so that patients who have a smattering of small brain metastases would be eligible. Now, patients with single large brain metastases, the reason that we excluded those from the trial was because we were afraid that if a patient didn't respond to the systemic therapy that we were going to give them, they could really then develop severe neurological symptoms. So, for patient safety, we used 20 millimeters as the upper level for inclusion. Some of the other trials that I mentioned earlier also excluded patients with very large lesions. Now, in practice, one certainly can do Gamma Knife therapy to the large lesions and leave the smaller ones untreated. So I think it actually is very applicable to clinical practice. Dr. Davide Soldato Thank you very much for that insight, because I think that sometimes criteria for clinical trials, they have to be very restrictive. But then we know that in clinical practice, the applicability of these results is probably broader. So, going a little bit further in the results of the study, I just wanted a little bit of comment from you regarding what you saw in terms of intracranial response rate and duration of response among patients who obtained a response from the combination treatment. Dr. Harriet Kluger So we were actually surprised. When we first designed this study, as I said earlier, we weren't trying to beat out ipilimumab and nivolumab. We were really just trying to exclude those patients who wouldn't have otherwise been eligible for ipilimumab and nivolumab because of edema or possibly even previous radiation necrosis. So it was designed to differentiate between a response rate of 34%, and I believe the lower bound was somewhere in the 20s, because that's what we'd seen in the previous pembrolizumab study. What we saw in the first 20 patients that we enrolled was actually a response rate that far exceeded that. And so we enrolled another cohort to verify that result because we were concerned about premature publishing of a result that we might have achieved just by chance. The two cohorts were very similar in terms of the response rates. And certainly this still needs to be verified in a second study with additional institutions. We did include the Moffitt Cancer Center, and the response rate with Moffitt Cancer Center was very similar to the Yale Cancer Center response rate. Now, your other question was about duration of response. So the other thing that we started asking ourselves was whether this high response rate was really because the administration of the anti-VEGF will decrease the gadolinium enhancement and therefore we might actually just be seeing prettier scans but not tumor shrinkage. And the way to differentiate those two is by looking at the duration of the response. Median progression-free survival was 2.2 years. That's pretty long. The upper bound on the 95% confidence interval was not reached. I can't tell you that the duration is as good as the duration would be when you give ipilimumab. Perhaps it is less good. This was a fairly sick population of patients, and it included some who might not have been able to receive ipilimumab and nivolumab. So it provides an alternative. I do believe that we need to do a randomized trial where we compare it to ipilimumab and nivolumab, which is the current standard of care in this patient population. We do need to interpret these results with caution. I also want to point out regarding the progression-free survival that we only gave four doses of anti-VEGF. So one would think that even though anti-VEGF has a long half-life of three or four weeks, two years later, you no longer have anti-VEGF effect, presumably. So it does something when it's administered fairly early on in the course of the treatment. Dr. Davide Soldato So, in terms of clinical applicability, do you see this combination of pembrolizumab and bevacizumab - and of course, as we mentioned, this was a phase 2 trial. The number of patients included was not very high, but still you saw some very promising results when compared with the combination of ipilimumab and nivolumab. So do you see this combination as something that should be given particularly to those patients who might not be able to receive ipilimumab and nivolumab? So, for example, patients who are very symptomatic from the start or require a high dose of steroids, or also to provide a quicker response in terms of patients who have neurological symptoms, or do you think that someday it could be potentially used for all patients? Dr. Harriet Kluger The third part of your question, whether it can be used someday for all patients: I think we need to be very careful when we interpret these results. The study was substantially smaller than the ipilimumab/nivolumab trial that was conducted by Bristol Myers Squibb. Also going to point out that was a different population of patients. Those were all frontline patients. Here we had a mix of patients who'd had previous anti-CTLA-4 and frontline patients. So I don't think that we can replace ipilimumab and nivolumab with these results. But certainly the steroid-sparing aspect of it is something that we really need to take into consideration. A lot of patients have lesions in locations where edema can be dangerous, and some of them have a hard time coming off the steroids. So this is certainly a good approach for those folks. Dr. Davide Soldato And coming back to something that you mentioned in the very introduction, when you said that there were two main problems, which was one, the problem of the edema, and the second one, the problem of the radionecrosis. In your trial, there was a fair percentage of patients who received some type of local treatment before the systemic one. So the combination of pembrolizumab and bevacizumab. And most of the patients received radiosurgery. So I just wanted a brief comment regarding the incidence of radionecrosis in the trial and whether that specific component of the combination with bevacizumab was reduced. And how do you think that this fares in terms of what we see in clinical practice in terms of radionecrosis? Dr. Harriet Kluger I'm not sure that we really reduced the incidence of radiation necrosis. We saw radiation necrosis here. We saw less of it than in the trial of pembrolizumab monotherapy, but these were also different patients, different time. We saw more than we thought that we were going to see. It was 27%, I believe, which is fairly high still. We only gave the four doses of bevacizumab. Maybe to really prevent radiation necrosis, you have to continue to give the bevacizumab. That, too, needs to be tested. The reason that we gave the four doses of bevacizumab was simply because of the cost of the bevacizumab at the time. Dr. Davide Soldato Thank you very much for that comment on radionecrosis. And I really think that potentially this is a strategy, so continuing the bevacizumab, that really makes a lot of sense, especially considering that the tolerability of the regimen was really very, very good, and you didn't see any significant or serious adverse events related to bevacizumab. So just wondering if you could comment a little bit on the toxicities, whether you had anything unexpected. Dr. Harriet Kluger There was one patient who had a microperforation of a diverticulum, which was probably related to the bevacizumab. It was conservatively managed, and the patient did fine and actually remains alive now, many years later. We had one patient who had dehiscence of a previous wound. So there is some. We did not see any substantial hypertension, proteinuria, but we only gave the four doses. So it is possible that if you give it for longer, we would see some side effects. But still, relative to ipilimumab, it's very, very well tolerated. Dr. Davide Soldato Yeah, exactly. I think that the safety profile is really different when we compare the combination of ipilimumab/nivolumab with the pembrolizumab/bevacizumab. And as you said, this was a very small trial and probably we need additional results. But still, these results, in terms of tolerability and safety, I think they are very interesting. So one additional question that I think warrants a little bit of comment on your part is actually related to the presence of patients with BRAF mutation and, in general, to what you think would be the best course of treatment for these patients who present with the upfront brain metastases. So this, it's actually not completely related to the study, but I think that since patients with BRAF mutation were included, I think that this warrants a little bit of discussion on your part. Dr. Harriet Kluger So we really believe that long-term disease control, particularly in brain metastases, doesn't happen when you give BRAF/MEK inhibitors. You sometimes get long-term control if you've got oligometastatic disease in extracranial sites and if they've previously been treated with a lot of immune checkpoint inhibitors, which wasn't the case over here. So a patient who presents early in the course of the disease, regardless of their BRAF status, I do believe that between our studies and all the studies that have been done on immunotherapy earlier in the course of disease, we should withhold BRAF/MEK inhibitors unless they have overwhelming disease and we need immediate disease control, and then we switch them very quickly to immunotherapy. Can I also say something about the toxicity question from the bevacizumab? I have one more comment to make. I think it's important. We were very careful not to include patients who had overt hemorrhage from brain metastases. So melanoma brain metastases relative to other tumor types tend to bleed, and that was an exclusion criteria. We didn't see any bleeding that was attributable to the bevacizumab, but we don't know for sure that, if this is widely used, that that might not be a problem that's observed. So I would advise folks to use extreme caution and perhaps not use it outside of the setting of a clinical trial in patients with overt hemorrhage in the melanoma brain metastases. Dr. Davide Soldato Thank you very much. I think that one aspect that is really interesting in the trial is actually related to the fact that you collected a series of biomarkers, both circulating ones, but also some that were collected actually from the tissue. So just wondering if you could explain a little bit which type of biomarkers you evaluated and whether you saw any significant results that could suggest higher or lower efficacy of the combination. Dr. Harriet Kluger Thank you for that. So yes, the biomarker studies are fairly exploratory, and I want to emphasize that we don't have anything that's remotely useful in clinical practice at this juncture. But we did see an association between vessel density in the tumors and improved response to this regimen. So possibly those lesions that are more vascular are more fed by or driven by VEGF, and that could be the reason that there was improved response. We also saw that when there was less of an increase in circulating angiopoietin-2 levels, patients were more likely to respond. Whether or not that pans out in larger cohorts of patients remains to be determined. Dr. Davide Soldato Still, do you envision validation of these biomarkers in a potentially additional trial that will evaluate, again, the combination? Because I think that the signals were quite interesting, and they really make sense from a biological point of view, considering the mechanism of action of bevacizumab. So I think that, yeah, you're right, they are exploratory. But still, I think that there is very strong biological rationale. So really I wanted to congratulate you on including that specific part and on reporting it. And so the question is, really, do you envision validation of these biomarkers in larger cohorts? Dr. Harriet Kluger I would hope to see that, just as I'd like to see validation of the clinical results as well. The circulating biomarkers are very easy to do. It's a simple ELISA test. And the vessel density on the tumor is essentially CD34 staining and units per area of tumor. Also very simple to do. So I'd love to see that happen. Dr. Davide Soldato Do you think that considering the quality of the MRI that we are using right now, it would be possible to completely bypass even the evaluation on the tissue? Like, are we going in a direction where we can, at a certain point, say the amount of vessels that we see in these metastases is higher versus lower just based on MRI results? Dr. Harriet Kluger You gave me an outstanding idea for a follow-up study. I don't know whether you can measure the intensity of gadolinium as a surrogate, but certainly something worth asking our neuroradiology colleagues. Excellent idea. Thank you. Dr. Davide Soldato You're welcome. So just moving a step further, we spoke a lot about the validation of these results and the combination. And just wanted your idea on what do you think it would be more interesting to do: if designing a clinical trial that really compares pembrolizumab/bevacizumab with ipilimumab and nivolumab or going directly for the triplet. So we know that there has been some type of exploration of triplet combination in metastatic melanoma. So just your clinical impression: What would you do as an investigator? Dr. Harriet Kluger So it's under some discussion, actually. It's very difficult to compare drugs from different companies in an investigator-initiated trial. Perhaps our European colleagues can do that trial for us. In the United States, it's much harder, but it can be done through the cooperative groups, and we are actually having some discussions about that. I don't have the answer for you. It would be lovely to have a trial that compared the three drugs to ipi/nivo and to pembrolizumab/bevacizumab. So a three-arm trial. But remember, these are frontline melanoma patients. There aren't that many of them anymore like there used to be. So accrual will be hard, and we have to be practical. Dr. Davide Soldato Yeah, you're right. And in the discussion of the manuscript, you actually mentioned some other trials that are ongoing, especially one that is investigating the combination of pembro and lenvatinib, another one that is investigating the combination of nivolumab and relatlimab. So just wondering, do you think that the molecule in terms of VEGF inhibition, so bevacizumab versus lenvatinib, can really make a difference or is going to be just a mechanism of action? Of course, we don't have the results from this trial but just wondering if you could give us a general comment or your opinion on the topic. Dr. Harriet Kluger So that's a really great question. The trial of pembrolizumab and lenvatinib was our answer to the fact that bevacizumab is not manufactured by the same company as pembrolizumab, and we're trying to give a practical answer to our next study that might enable us to take this approach further. But it does turn out from our preclinical studies that bevacizumab and VEGF receptor inhibition aren't actually the same thing in terms of the effects on the blood-brain barrier or the perilesional tumor microenvironment in the brain. And these studies were done in mice and in in vitro models. Very different effects. The lenvatinib has stronger effect on the tumors themselves, the tumor cells themselves, than the bevacizumab, which has no effect whatsoever. But the lenvatinib doesn't appear to tighten up that blood-brain barrier. Dr. Davide Soldato Thank you. I think that's very interesting, and I think it's going to be interesting to see also results of these trials to actually improve and give more options to our patients in terms of different mechanism of action, different side effects. Because in the end, one thing that we discussed is that some combination may be useful in some specific clinical situation while others cannot be applicable, like, for example, an all immunotherapy-based combination. Just one final comment, because I think that we focused a lot on the intracranial response and progression-free survival. You briefly mentioned this but just wanted to reinforce the concept. Did you see any differences in terms of intracranial versus extracranial response for those patients who also had extracranial disease with the combination of pembro and bevacizumab? Dr. Harriet Kluger So the responses were almost always concordant. There were a couple of cases that might have had a body response and not an intracranial response and vice-versa, but the vast majority had concordant response or progression. We do believe that it's a biological phenomenon. The type of tumor that tends to go to the brain is going to be the type of tumor that will respond to whatever the regimen is that we're giving. In the previous trial also, we saw concordance of responses in the body and the brain. Dr. Davide Soldato Thank you very much. Just to highlight that really the combination is worth pursuing considering that there was not so much discordant responses, and the results, even in a phase 2 trial, were very, very promising. So thank you again, Dr. Kluger, for joining us today and giving us a little bit of insight into this very interesting trial. Dr. Harriet Kluger Thank you for having me. Dr. Davide Soldato So we appreciate you sharing more on your JCO article titled "Phase 2 Trial of Pembrolizumab in Combination with Bevacizumab for Untreated Melanoma Brain Metastases," which gave us the opportunity to discuss current treatment landscape in metastatic melanoma and future direction in research for melanoma brain metastasis. If you enjoy our show, please leave us a rating and review and be sure to come back for another episode. You can find all ASCO shows at asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

S12 Ep28: Ivonescimab Improves PFS vs Pembrolizumab in Advanced PD-L1+ NSCLC: With Xiuning Le, MD, PhD

Play Episode Listen Later Mar 24, 2025 11:22

In today's episode, supported by Summit Therapeutics, we had the pleasure of speaking with Xiuning Le, MD, PhD, about the use of ivonescimab (SMT112) in patients with PD-L1–positive non–small cell lung cancer (NSCLC). Dr Le is an associate professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Internal Medicine at The University of Texas MD Anderson Cancer Center in Houston. The phase 3 HARMONi-2 trial (NCT05499390) investigated ivonescimab vs pembrolizumab (Keytruda) in patients with locally advanced or metastatic, PD-L1–positive NSCLC without sensitizing EGFR mutations or ALK translocations. At the preplanned interim analysis, at a median follow-up of 8.7 months (IQR, 7.1-10.3), the median progression-free survival was significantly longer in the ivonescimab arm (n = 198) vs the pembrolizumab arm (n = 200), at 11.1 months (95% CI, 7.3-not estimable) vs 5.8 months (95% CI, 5.0-8.2), respectively (stratified HR, 0.51; 95% CI, 0.38-0.69; 1-sided P < .0001). The objective response rates were 50% (95% CI, 43%-57%) and 39% (95% CI, 32%-46%) in these respective arms. In our exclusive interview, Dr Le discussed the rationale for the HARMONi-2 trial, key findings from the study, and where these findings position the potential role of ivonescimab in the PD-L1–positive NSCLC treatment paradigm.

university phd md improves internal medicine md phd egfr alk nsclc texas md anderson cancer center pd l1 keytruda pembrolizumab iqr summit therapeutics neck medical oncology

How to Treat Renal Cell Carcinoma (RCC) using a Treatment Algorithm with Dr. Katy Beckermann

current treatments algorithms keynote drs rahul cancer research rcc ngs pd l1 tki renal cell carcinoma pembrolizumab ctdna

Play Episode Listen Later Mar 17, 2025 19:56

Join us for an insightful episode of the Oncology Brothers podcast as we dive deep into the world of renal cell carcinoma (RCC) with Dr. Katy Beckermann, the Medical GU Director of Cancer Research at Tennessee Oncology. In this episode, hosts Drs. Rahul & Rohit Gosain, practicing medical oncologists, discuss the latest advancements in RCC treatment, including: •⁠ ⁠The role of Pembrolizumab in the adjuvant setting based on the Keynote 564 study and its implications for early-stage disease. •⁠ ⁠Current treatment paradigms for metastatic RCC, including dual checkpoint inhibitors, TKI with immunotherapy, and single-agent options. •⁠ ⁠The importance of patient characteristics and IMDC risk categorization in treatment decisions. •⁠ ⁠Insights into sequencing therapies, including the use of Belzutifan for refractory disease and the management of side effects. •⁠ ⁠The role of ctDNA, PD-L1 testing, and NGS in RCC. Whether you're a community oncologist or simply interested in the latest in cancer care, this episode is packed with valuable information to help you stay informed and provide the best care for your patients. YouTube: https://youtu.be/Bbv9N7-YKIM Follow us on social media: •⁠ ⁠X/Twitter: https://twitter.com/oncbrothers •⁠ ⁠Instagram: https://www.instagram.com/oncbrothers •⁠ Website: https://oncbrothers.com/ Don't forget to like, subscribe, and leave a review to let us know how we're doing and how we can continue to support you in the community!

S12 Ep18: Neoadjuvant MVAC/Pembrolizumab Generates Unprecedented pCR Rates in Non-Urothelial MIBC: With Chandler Park, MD; Petros Grivas, MD, PhD; and Ruben Raychaudhuri, MD

Acredite Se Quiser Podcast

Play Episode Listen Later Feb 26, 2025 20:33

In this episode of Oncology Unplugged, a podcast series from OncLive and MedNews Week, podcast host Chandler Park, MD, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was joined by Petros Grivas, MD, PhD; and Ruben Raychaudhuri, MD, to talk about a pilot trial investigating neoadjuvant accelerated methotrexate, vinblastine,doxorubicin, and cisplatin (aMVAC) plus pembrolizumab (Keytruda) in patients with non-urothelial muscle-invasive bladder cancer, findings from which were presented at the 2025 Genitourinary Cancers Symposium. Dr Grivas is clinical director of the Genitourinary Cancers Program and a professor in the Clinical Research Division at Fred Hutchinson Cancer Center, as well as a professor in the Division of Hematology and Oncology at the University of Washington School of Medicine in Seattle. Dr Raychaudhuri is an assistant professor in the Clinical Research Division at Fred Hutchinson Cancer Center, as well as an assistant professor in the Division of Hematology and Oncology at the University of Washington School of Medicine. In their exclusive conversation, Drs Park, Grivas, and Raychaudhuri discussed key efficacy and safety findings from this study; the need for conducting dedicated research in bladder cancer patient populations with variant histologies; and the potential of biomarkers, such as HER2 expression, to improve the bladder cancer treatment paradigm in the future.

university phd seattle medicine kentucky park md louisville unprecedented oncology md phd generates hematology washington school petros her2 neoadjuvant keytruda pembrolizumab mvac mibc genitourinary cancers symposium clinical research division onclive

191 - Conspirações da Indústria Farmacêutica.

Play Episode Listen Later Jan 30, 2025 76:51

Existem muitos mitos e fake news sobre a indústria farmacêutica, como a existência de uma vacina contra o câncer e de que a vacina da covid estava causando mal as pessoas. O que de fato é real nisso tudo? Aperte o play e venha descobrir o que é verdade e mentira dentro dessa imensa quantidade de notícias publicadas pelo mundo! RECOMENDAMOS ESCUTAR COM FONES DE OUVIDO Se você gosta do nosso trabalho, contribua com o apoia-se e participe do nosso grupo exclusivo para apoiadores ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Apoia-se Acredite se Quiser Podcast⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Apoia-se Portal Fenomenum⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Patreon Acredite se Quiser⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Siga e avalie o Acredite Se Quiser nas plataformas de streaming! Siga-nos nas redes sociais: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Instagram⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Twitter⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Perfil do Setembro no X ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Venda livro Relatos Alienígenas na Amazon ⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠E-mail para contato: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠acreditesequiserpodcast@gmail.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Conheça a nova loja SkynWalker na Reserva Ink⁠⁠ Links citados no episódio: - Ivermectin and Pembrolizumab for the Treatment of Metastatic Triple Negative Breast Cancer - Ivermectin, a potential anticancer drug derived from an antiparasitic drug - mRNA vaccine in cancer therapy: Current advance and future outlook - Vaccine Therapies for Cancer: Then and Now - Evidence on the effectiveness of homeopathy for treating health conditions - Cancer Vaccine Therapeutics: Limitations and Effectiveness-A Literature Review - Vaccine Safety: Myths and Misinformation - Does Vaccination Increase the Risk of Autism Spectrum Disorder? - Moving past the vaccine/autism controversy - to examine potential vaccine neurological harms - Epilepsy and cannabidiol: a guide to treatment - COVID-19: The disease, the vaccine and the heart - COVID-19 Severity: Lung-Heart Interplay - Homeopathy: insubstantial doctrine of salvation Learn more about your ad choices. Visit megaphone.fm/adchoices

covid-19 moving risk current treatments conhe siga mrna existem epilepsy utica ivermectin autism spectrum disorder aperte conspira farmac acredite apoia amazone pembrolizumab

Navigating Immune-Related Toxicities: Insights on Monitoring, Treatment, and Prevention

ProCE: The Pharmacy Practice Podcast

Play Episode Listen Later Jan 10, 2025 30:03

In this episode, Alexa Basilio, PharmD, BCOP and Jessica Davis, PharmD, BCOP, CPP discuss immune-related adverse events and toxicities among patients using immune checkpoint inhibitors. This overview will include discussion about: How and when to monitor and treat mild vs severe immune-related toxicitiesThe art of balancing and tapering low-dose and high-dose corticosteroidsDifferentiating between immune-related and chemotherapy- or targeted therapy–associated adverse events for optimal management approachesInvolvement of multidisciplinary teams early during treatment to prevent immune-related adverse eventsImportance of educating patients, caregivers, and providers on immune-related toxicitiesPresenters: Alexa Basilio, PharmD, BCOPUniversity of Florida College of Pharmacy Oncology Pharmacy Specialist McKesson, The US Oncology NetworkTampa, Florida Jessica Davis, PharmD, BCOP, CPP Levine Cancer InstituteClinical Pharmacist Coordinator, Adult Hematology/OncologyAtrium Health Levine CenterCharlotte, North Carolina Link to full program: https://bit.ly/3We4HJy

SABCS 2024 Highlights - INSEMA, KEYNOTE-522, OlympiA

keynote drs pcr ucsf rahul brca pembrolizumab san antonio breast cancer symposium olaparib

Play Episode Listen Later Jan 9, 2025 20:39

Welcome to another episode of the Oncology Brothers podcast! In this episode, hosts Drs. Rahul & Rohit Gosain are joined by Dr. Laura Huppert from UCSF to discuss key highlights from the San Antonio Breast Cancer Symposium 2024. We dive into three crucial studies: 1.⁠ ⁠INSEMA Study: Explore the findings on the potential omission of axillary surgery in early-stage hormone receptor-positive breast cancer and its implications for patient quality of life. 2.⁠ ⁠KEYNOTE-522 Update: Learn about the latest insights on the use of Pembrolizumab in triple-negative breast cancer, including the search for predictive biomarkers and the impact of achieving pathological complete response (PCR). 3.⁠ ⁠OlympiA Study Update: Discover the updated results on the use of Olaparib in BRCA-positive patients, highlighting its significant benefits in invasive disease-free survival and overall survival. Join us as we unpack these important studies and their implications for clinical practice. Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers! Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

S12 Ep2: Pembrolizumab Plus Preoperative Radiotherapy and Surgery Improves DFS in Soft-Tissue Sarcoma: With Yvonne Mowery, MD, PhD

university phd pennsylvania md surgery improves md phd sarcoma soft tissue radiotherapy preoperative mowery pembrolizumab

Play Episode Listen Later Jan 7, 2025 16:23

In today's episode, we had the pleasure of speaking with Yvonne Mowery, MD, PhD, about the phase 2 SU2C-SARC032 trial (NCT03092323) investigating the addition of pembrolizumab to preoperative radiotherapy and surgery in patients with soft-tissue sarcoma. Dr Mowey is a physician scientist and an associate professor of radiation oncology at the University of Pittsburgh Medical Center Hillman Cancer Center in Pennsylvania. In our exclusive interview, Dr Mowery discussed unmet needs for patients with soft-tissue sarcoma that prompted the initiation of this research, key efficacy and safety findings from the trial, and potential next steps for investigating the treatment regimen in this patient population.

Transcriptome and ctDNA Associates with Pembrolizumab Benefit

JCO Precision Oncology Conversations

Play Episode Listen Later Dec 18, 2024 23:19

JCO PO authors Dr. Philippe Bedard (Staff Medical Oncologist at Princess Margaret Cancer Centre and Professor of Medicine at University of Toronto) and Dr. Alberto Hernando Calvo (Medical Oncologist at Vall d´Hebron University Hospital) share insights into their JCO PO article, “Combined Transcriptome and Circulating Tumor DNA Longitudinal Biomarker Analysis Associates With Clinical Outcomes in Advanced Solid Tumors Treated With Pembrolizumab,” one of the top downloaded articles of 2024. Host Dr. Rafeh Naqash and Drs. Bedard and Hernando Calvo discuss how combined transcriptome and ctDNA longitudinal analysis associates with pembrolizumab outcomes. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma. Today we are excited to be joined by Dr. Philippe Bedard, Staff Medical Oncologist at the Princess Margaret Cancer Center and Professor of Medicine at the University of Toronto, as well as by Dr. Alberto Hernando-Calvo, Medical Oncologist at the Vall d'Hebron University Hospital, both authors of the JCO Precision Oncology article titled, “Combined Transcriptome and Circulating Tumor DNA Longitudinal Biomarker Analysis Associates With Clinical Outcomes in Advanced Solid Tumors Treated With Pembrolizumab.” Thank you for joining us today. Phil and Alberto. Dr. Alberto Hernando-Calvo: Thank you. Dr. Philippe Bedard: Great to be with you. Thanks for having us. Dr. Rafeh Naqash: One of the reasons we do this podcast, as some of the listeners who listen to this podcast regularly may know, is to bring in novel approaches and try to understand how the field is moving towards a space where we are understanding biomarkers better. So your manuscript that was published in JCO Precision Oncology fulfills many of those criteria. And interestingly enough, I was at a conference at the Society for Immunotherapy of Cancer last month earlier in November and a lot of excitement at SITC was revolving around novel transcriptomic biomarkers, proteomic biomarkers or imaging based biomarkers. So could you tell us a little bit about why you started looking at biomarkers? This is an extremely competitive field. Why did you think that looking at the transcriptome is somewhat different from or more interesting from tumor mutational burden PDL-1 than other biomarkers that we currently use? And that question is for you Alberto to start off. Dr. Alberto Hernando-Calvo: So I think gene expression profiles may have a predictive performance as compared to already existing biomarkers and this was one of the points that we describe in our manuscript. The gene expression signature that we developed back in 2019 at Vall d'Hebron Institute of Oncology was initially developed based on over 45 different tumor types and tested in over 1000 patients treated with antiPD-1 and anti PDL-1. And back then and in this manuscript, we proved that for instance the gene expression signature VIGex that we developed has a potential complementary role to other predictive biomarkers. In this case, we observe this predictive power with ctDNA dynamics and we then see a correlation with other existing biomarkers such as tumor mutational burden. So I don't think we need to use one or the other, but rather they may have additive predictive power. So we need to better individualize predictive biomarkers based on tumor types and select the best combination possible to improve the performance. Dr. Rafeh Naqash: I completely agree that one size does not fit all, especially in the landscape of immunotherapy. From your perspective, when you developed the original signature, how did you choose what genes to look at? I looked at the manuscript, on the methodology side, some of the signatures are pro-inflammatory STING interferon gamma based, so how did you try to identify that these are the 7 to 10 or whatever number of signatures on the transcriptome side? And then why did you try to combine it with ctDNA based changes? Dr. Alberto Hernando-Calvo: Back in our initial manuscript, published in Med from Cell Press, we developed the VIGex gene expression signature, as I mentioned, with taking into consideration over 1000 tumor samples from FFPE that we can consider real world samples because they are from real patients coming from the clinic notes as part of real investigational protocol doing or performing biopsies on patients. We did observe after doing a VIGex research and doing different tests, we eventually collected these 12 different genes. Because there is a combination of both genes involved in the interferon gamma pathway, we have genes associated with Tregs as well as T cell memory cells. So it's not only looking at genes that are associated with T cell activation or CD8+ T cell infiltration, but also looking at genes that may be overactivated, overexpressed, an immunosuppressive tumor microenvironment. So it was both selecting genes, the minimum number of genes to do it more scalable and having the minimum dataset of genes and including in the signature genes that are already at targets for immune sequent inhibitors or are being tested in immunotherapy combinations. Dr. Rafeh Naqash: Thank you. And Phil, for the sake of our listeners, could you elaborate upon this aspect of using ctDNA? So this was tumor-informed ctDNA from what I understood in the manuscript. You guys basically try to use it to understand changes in the ctDNA with treatment and then try to combine it with the transcriptome signature. How did the idea come up initially and how did you plan on combining this with an RNA-based signature? Because I have seen manuscripts and other data where people are either using one or the other, but not necessarily both together. So how did you guys come up with that idea? Dr. Philippe Bedard: Well, we thought that this was a great opportunity to look at the combination of the transcriptome as well as the ctDNA dynamics because we had run an investigator-initiated phase 2 clinical trial called INSPIRE at our institution at Princess Margaret from 2016 to 2018, where patients across five different tumor groups received single agent pembrolizumab. And we really did a deep dive on these patients where there were tumor biopsies before and while on treatment. We did exome sequencing, we did RNA sequencing to capture the transcriptome. And in a prior analysis, we had partnered with Natera to look at their Signatera assay, which is a bespoke ctDNA assay, to look at ctDNA dynamics using this test and the association with response outcomes as well as survival outcomes. So we thought that this was a really unique data set to try and address the question of whether or not there was complementarity in terms of looking at the transcriptome and transcriptome signatures of IO benefit together with the ctDNA dynamics. Dr. Rafeh Naqash: From a patient treatment standpoint, it sounded like you mostly tried to include individuals who were treated with pembrolizumab. Did this not include individuals who were treated with chemoimmunotherapy or chemotherapy with pembrolizumab? Just pembrolizumab alone? And if that's the case, some of the tumor types there included, from what I remember, ovarian cancer and some other unusual cancers that don't necessarily have approvals for single agent pembrolizumab, but perhaps in the TMB-high setting. So can you elaborate on the patient selection there for the study? Dr. Philippe Bedard: Yeah, that's a great question. So at the time that the study was designed in 2015, this was really the early days of immune checkpoint inhibitor therapy, so we didn't have the approvals that we have now in specific tumor types for immunotherapy and chemotherapy combinations. So when the study was designed as an investigator initiated clinical trial, the idea was really to capture patients across different tumor types - so head and neck squamous cell carcinoma, malignant melanoma, ovarian cancer, triple negative breast cancer, and a kind of mixed histology solid tumor cohort, where we knew that there were some patients who were going to be immunotherapy responsive, where there was already approvals or evidence of single agent activity, and others where the responses were more anecdotal, to try and understand in a phase 2 clinical trial with kind of a deep dive, which patients benefited from treatment and which didn't. Dr. Rafeh Naqash: Interesting approach. Going to the results, Alberto, could you help us understand some of the important findings from these data? Because there's different sections of how you tried to look at the response rates, the survival, looking at the immune deconvolution, if you could explain that. Dr. Alberto Hernando-Calvo: So the first thing that we tried was to further confirm the external validation of this immune gene expression signature, VIGex in the INSPIRE asset. So what we observed at VIGex-Hot, the category defined by VIGex-Hot tumor microenvironment, was associated with better progression free survival. After including that in a multivariable analysis adjusted by other biomarkers such as TMB, PDL-1 or tumor type, this was also confirmed for overall survival. So then the next step was to really try to hypothesize if the addition of ctDNA dynamics, taking into consideration the ctDNA quantification at baseline as compared to cycle three, if those dynamics could further improve the predictive performance of VIGex categories taken in the baseline samples. What we did observe was that, for instance, VIGex-Hot tumors in baseline tumor samples that were having a ctDNA decrease, as I mentioned before on cycle three assessment as compared to baseline, were having both better progression free survival and better prognosis overall. Another important finding was the evaluation of response rate across tumor types considering both biomarkers. I would say the most important finding is that when we were considering a cold tumor microenvironment in baseline samples before pembrolizumab initiation plus an increase in ctDNA values, what we observed is that those patients were having a 0% response rate. So this may help as a future strategy either for intensification of immunotherapy regimens in a more individualized way or for an early stop to immunotherapy and try to avoid financial toxicities as well as toxicities for our patients. Dr. Rafeh Naqash: From the data that you showed, it seems that there was a strong correlation, as you sort of mentioned, between individuals that had ctDNA clearance and baseline immune pro-inflammatory signatures. So do you really need the transcriptome signature or could the ctDNA just serve as an easy quick surrogate? Because from a cost standpoint, doing whole transcriptome sequencing or more RNA sequencing or tissue standpoint, where tissue is often limited, can become a big issue. So do you think that validation of this may perhaps more revolve around using ctDNA as an easier metric or surrogate? Or am I overestimating the utility of ctDNA? Dr. Philippe Bedard: I think it's a really good question. In our data set which was relatively small, there were 10 patients who had ctDNA clearance, meaning ctDNA that was positive at baseline was not detected. And so 9 out of those 10 patients, as you alluded to, were VIGex-Hot. So the question is a good one, could you do the same with just ctDNA clearance alone, particularly in identifying these patients who really do well, who have long term disease control on immunotherapy? I think it's a tough question to answer because the field is also changing in terms of sensitivity of detection of ctDNA tests. So we know now that there are newer generations of tests which can detect even at logs down in terms of allele variants in the circulation. So I think we need more data to address the question. I think it is important as to what is the best test, what is the endpoint that we should be using from a drug development point of view in terms of really trying to push and understand which treatment regimens are the most effective and have early readouts in terms of activity. Because we all recognize in the clinic that radiographic response doesn't tell the whole story, especially early radiographic assessments using RECIST or other criteria that we apply in clinical trials. Dr. Rafeh Naqash: From a clinical trial standpoint, we often talk about validation of these studies. You may have heard of other tests where, for example, the NCI iMatch, which is incorporating transcriptome sequencing based approach to stratify patients as an integral biomarker for treatment stratification. Is that something that you guys are thinking of using, this approach where individuals who are signature highly inflamed perhaps get lesser therapies or there's a de-intensification of some sort similar to what people are trying to do with ctDNA-based approaches? Dr. Philippe Bedard: I think that's a great question. I think it makes a lot of sense. And certainly, with the new wave antibody drug conjugates in terms of identifying patients who have expression of targets for antibody drug conjugates, that's very attractive as an approach because we don't necessarily have IHC markers for all of the different targets of antibody drug conjugates. We don't necessarily have IHC markers to completely understand different contributions to the tumor microenvironment and whether or not tumors are inflamed. But it's also a challenging approach too because RNA-seq currently is not a routine clinical test. Sometimes there are issues, particularly in patients who have stored specimens that are formalin-fixed and paraffin-embedded in terms of the quality of the RNA for RNA sequencing. And it's not always feasible to get pre-treatment biopsies and turn them around in an approach. So I think it is an attractive approach for clinical trials, but it's a hypothesis that needs to be tested. It's not something that is ready for clinical prime time today in 2024. Dr. Rafeh Naqash: One of the other interesting observations that I came across in your manuscript was that tumor mutational burden, interestingly, did not correlate with signature high tumors. What is the explanation for that? Because generally you would expect a TMB high to perhaps also have an immune gene high signature. Could it have something to do with the tumor types because there was a heterogeneous mixture of tumor type? Or I'm not sure. What else could you possibly think of that you didn't see those correlations or just sample size limitations? Dr. Alberto Hernando-Calvo: Yes. So our findings are consistent with prior data suggesting for instance T cell inflamed gene expression profile was also not correlated with tumor mutational burden and both biomarkers in a prior publication. So to have additive predictive performance for identifying patients most likely to benefit from anti PD-1 regimen, so we somehow were expecting this observation, the fact that both biomarkers are not very correlated. Dr. Rafeh Naqash: So given the proof of concept findings from your study, Phil, what is the next interesting step that you guys are thinking of to expand this? Would you think that a nivolumab-ipilimumab treated cohort would have similar findings? Or is this a treatment specific single agent immunotherapy specific correlation that you found versus something else that you may find in a nivo-ipi cohort or a doublet immune checkpoint cohort? Dr. Philippe Bedard: The findings are really hypothesis generating. They require additional validation. And you're quite right, there may be nuances in terms of specific tumor types, combinations with other immunotherapy or combinations with chemotherapy or other agents. So I think it would be great if there are other data sets that are collecting this type of information that have ctDNA dynamics and also have transcriptome and potentially exome or genome analysis to look at these types of questions because the field is moving quickly and we really need more data sets in order to understand some of the nuances and greater numbers to validate the signals that we see. Dr. Rafeh Naqash: And one thing, as you said, the field is definitely moving very quickly. I was meeting with a company an hour back and they have an imaging-based approach using fresh tissue to look at pharmacodynamic biomarkers. And I used to work in the NCI with a group that was very interested and they developed an immuno-oncology pharmacodynamic panel that has been used and published in a few clinical trials where they did phosphorylation status. So the final theme that comes out of most of these research based studies that are being done is that one size does not fit all. But the question that comes to my mind is how many things do you necessarily need to combine to get to a predictive biomarker that is useful, that is patient centric, and that perhaps is able to identify the right therapy for the right patient. What is your take on that, Phil? Dr. Philippe Bedard: Yeah, that's a great question too. The challenge is it depends on the context in terms of what degree of positive predictive value do you need as well as the negative predictive value to drive clinical decisions. So I think in certain situations where you don't have other approved treatment options and with a therapy that is potentially low toxicity and low financial toxicity, then I think the bar is very high in terms of being able to really confidently identify that patients aren't going to benefit. I think the nuance and the challenge becomes when you move into earlier lines of therapy, or when you talk about combinations of agents, or trying to understand within the context of other available options, particularly with treatments that have significant side effect profiles as well as financial risks, then it becomes a much more nuanced question and you really need comparative studies to understand how it fits versus the existing treatment paradigm. So I'm not really answering your question with a specific number because I think it's hard to give you a number. Some of that we also need input from patients in terms of what kind of level of validation do you need and what kind of level of discrimination do you need in order to drive decisions that are meaningful for them. Dr. Rafeh Naqash: Definitely early days, as you pointed out. More and more work in this field will hopefully lead us in the direction that we all want to go in. Now, going to a different aspect of this podcast, which is trying to understand the trajectories for both of you, Phil and Alberto. And as you mentioned, this project seemed to have started in 2015. So I'm guessing there's a history there between Princess Margaret and Vall d'Hebron. Could you highlight that a little bit? And then perhaps, Alberto, after that you could tell us a little bit about your career when you worked at Princess Margaret as a fellow and then now back at Vall d'Hebron. Phil, you as well. Dr. Philippe Bedard: So absolutely. We have a long history of collaborating with Vall d'Hebron in Barcelona. It's really a great cancer institution with a lot of like minded individuals. We have a formal partnership and we have a lot of informal links in terms of scientists and clinicians who we work with and who we collaborate with on early phase clinical trials, as well as through different investigator networks and other translational projects. So this was really how this collaboration came about and we were fortunate to have Alberto, who came to work with us for two years and brought this great idea of looking at this signature they had developed at Vall d'Hebron in their phase one group and applying it to a data set that we had through the INSPIRE clinical trial. Dr. Rafeh Naqash: Sounds like a very successful academia-academic collaboration, which is very nice to see. So, Alberto, could you tell us a little bit about your career trajectory and how you ended up at Princess Margaret and then back at Vall d'Hebron and what you do currently? Dr. Alberto Hernando-Calvo: Yes. So I did my oncology residency at Vall d'Hebron in Barcelona, Spain. Then I decided to further specialize in early drug development as well as head and neck cancer oncology. So I decided to pursue a clinical research fellowship under the supervision of Phil Bedard, among others. And so we decided to further validate the signature that we had developed both in the cancer genomic lab at Vall d'Hebron Institute of Oncology and the phase one unit at Vall d'Hebron, and apply the signature that have been originally tested in patients receiving anti PD-1 or anti PDL-1 combinations in early phase clinical trials. In the phase 2 clinical trial of INSPIRE, where we also had ctDNA dynamics and allowed us to test both biomarkers and see that additive predictive power when we were using both. That was one of my research topics under the mentorship of Dr. Bedard and my fellowship at Princess Margaret. And this was one of the manuscripts describing all the findings of this collaboration between Vall d'Hebron and Princess Margaret Cancer Center. Dr. Rafeh Naqash: And then, Phil, if you could highlight some of the things that you've done over the course of your career and perhaps some advice for early career junior investigators and trainees. Dr. Philippe Bedard: I finished my oncology, medical oncology training at the University of Toronto in 2008. And then I did a breast cancer fellowship in Brussels at Breast International Group. At the time, I was really intrigued because it was really kind of the early days of microarray and RNA signatures in terms of expressing signatures were being used as part of a clinical trial that BIG was running called the MINDACT Study. And so when I finished my fellowship, I came back to Princess Margaret, started on staff. I've been here now for 15 years. I was fortunate to work with the phase 1 group and kind of my career has sort of morphed in terms of early drug development as well as genomics. I've been involved with the American Association for Cancer Research project GENIE, where I'm the current chair. This is really an international data sharing project with panel based sequencing, which both Princess Margaret and Vall d'Hebron have contributed to. And I've been fortunate to work with a number of really talented early career investigators like Alberto, who spend time with us in our drug development program and launched transitional research projects that leverage some existing data sets at their own institutions and also bring together with different research groups at our institution to lead to publications like this one. Dr. Rafeh Naqash: Thank you so much. This was very exciting. Phil and Albert, thanks for joining us today and thank you for allowing us to discuss your interesting manuscript and hopefully we'll see more of this biomarker work from you guys in the near future, perhaps published in JCO Precision Oncology. And thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

KEYNOTE-A18 Overall Survival Results: Pembrolizumab and Chemoradiotherapy with Domenica Lorusso

IJGC Podcast

Play Episode Listen Later Nov 18, 2024 32:27

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Dr. Domenica Lorusso to discuss KEYNOTE-A18 Overall Survival Results: Pembrolizumab and Chemoradiotherapy. Dr. Domenica Lorusso, MD, PhD, directs the Gynaecological Oncology Unit at Humanitas Hospital, Milan, and holds a Full Professorship in Obstetrics and Gynaecology at Humanitas University, Rozzano, Milan. She has led/participated in approximately 250 phase I-IV clinical trials. Currently overseeing more than 60 studies as Principal Investigator, Dr. Lorusso also chairs the Clinical Trials Committee of the MITO Group. She serves on the Board of Directors of the GCIG and is an active member of ENGOT, where she chairs the Gynecological Cancer Academy. Additionally, she sits on the Board of Directors of the ESGO. With around 300 international oncology publications and contributions to national and international treatment guidelines, her primary objectives are to ensure optimal patient care, foster clinical research, and advance international collaborations and education in the field. Highlights: In a phase 3 trial (ENGOT-cx11/GOG-3047/KEYNOTE-A18), pembrolizumab added to chemoradiotherapy significantly improved progression-free survival and overall survival for patients with locally advanced, high-risk cervical cancer. Patient Group: 1060 patients with FIGO 2014 stage IB2–IVA cervical cancer from 30 countries were randomized to receive pembrolizumab with chemoradiotherapy or placebo with chemoradiotherapy. Overall Survival: At a median follow-up of 29.9 months, the 36-month overall survival rate was 82.6% in the pembrolizumab group versus 74.8% in the placebo group, with a hazard ratio for death of 0.67 (95% CI 0.50–0.90; p=0.0040). Safety Profile: Grade 3 or higher adverse events were reported in 78% of pembrolizumab-treated patients versus 70% in the placebo group, with higher rates of potentially immune-mediated adverse events in the pembrolizumab group (39% vs. 17%). Conclusion: These findings confirm pembrolizumab plus chemoradiotherapy as an effective and potentially new standard of care for locally advanced cervical cancer.

director phd board md survival keynote obstetrics gog principal investigators domenica figo gynaecology lorusso pembrolizumab rozzano editor in chief dr humanitas university engot

FDA D.I.S.C.O. Burst Edition: FDA approval of Keytruda (pembrolizumab) for unresectable advanced or metastatic malignant pleural mesothelioma

FDA Drug Information Soundcast in Clinical Oncology (D.I.S.C.O.)

Play Episode Listen Later Nov 14, 2024 3:30

Listen to a soundcast of the 9.17.2024 FDA approval of Keytruda (pembrolizumab) for unresectable advanced or metastatic malignant pleural mesothelioma.

fda disc burst malignant fda approval metastatic mesothelioma pleural keytruda pembrolizumab unresectable

Adjuvant Pembrolizumab for High-Risk, dMMR Endometrial Cancer

treatments cancer treatment bcg md anderson cancer center bladder cancer pembrolizumab new advances

Play Episode Listen Later Oct 16, 2024 16:40

Dr. Shannon Westin and her guest, Dr. Brian Slomovitz discuss the article “Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy For Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors” recently published in the JCO and presented at the 2024 International Gynecologic Cancer Society. TRANSCRIPT The guest's disclosures can be found in the transcript. Dr. Shannon Westin: Hello, and welcome to another episode of JCO After Hours, the podcast where we get in depth on manuscripts and literature published in the Journal of Clinical Oncology. I'm your host, Shannon Westin, gynecologic oncologist and JCO Social Media Editor by trade. I am thrilled because we are going to be talking about gynecologic cancer today. So, this is my jam. And specifically, we're going to be talking about a manuscript that's a simultaneous publication in the Journal of Clinical Oncology and presented at the Annual Meeting of the International Gynecologic Cancer Society on October 16, 2024. And this is “Pembrolizumab or Placebo, Plus Adjuvant Chemotherapy, With or Without Radiotherapy for Newly Diagnosed High Risk Endometrial Cancer: Results in Mismatch Repair Deficient Tumors.” This is affectionately the KEYNOTE-B21 trial, also known as the GOG-3053 trial and the ENGOT-en11 trial. And we are joined today by the primary author in this manuscript, Dr. Brian Slomovitz, who is the Director of Gynecologic Oncology at Mount Sinai Medical Center in Miami Beach, Florida, and the clinical trial advisor in uterine cancer for the Gynecologic Oncology Group foundation. Welcome, Brian. Dr. Brian Slomovitz: Hey, thanks, Shannon, so much. It's a pleasure to be here. And thanks for giving us the opportunity to discuss this trial. Dr. Shannon Westin: Yes, it's a great trial and I'm so excited to talk about it. And I think we'll start just because this is a broad group that listens to this podcast, they're not all GYN oncologists, experts like yourself, so can you just level set a little bit and speak a bit about the incidence and mortality of endometrial cancer overall and the recent trends in this disease? Dr. Brian Slomovitz: Yeah, sure. So, and it is nice to speak about gynecologic cancers, as we know, endometrial cancer was and still is the most common of all gynecologic cancers. The numbers are going up. Right now, there's about 65,000 to 70,000 cases each year in the US diagnosed with endometrial cancer. The numbers are going up. A lot of its obesity related, some other factors, but as the population gets less healthy, those are some of the risk factors for the disease. The thing that, however, is quite surprising is that we're seeing the deaths due to endometrial cancer going up as well, while for other diseases, we're making slow, steady steps to try to decrease the mortality we're actually seeing an increase in mortality. And the most discouraging point, Shannon, as you know is the number of deaths from endometrial cancer is going to outnumber the number of deaths from ovarian cancer if it hasn't done it already. I mean, now's the time. So, we really need to come up with better treatment strategies to everything to decrease the incidence of disease, to help with prevention, but for those poor women who are diagnosed, to come up with better treatment options so we don't have to keep this increasing trend in mortality. Dr. Shannon Westin: Absolutely. And I think some of that is related and we don't need to get on a soapbox here, but the amount of funding that goes towards research in endometrial cancer, and of course you, you have been leading the way and really trying to get a ton of trials in this space and getting our industry partners and our government partners to really support this. So really just commending you on how much you've worked on, on this area. And to that end, we've had a huge renaissance with immunotherapy and endometrial cancer, a lot of really big trials. Why don't you give the audience a rundown of where, so far, this seems to be best utilized for people with endometrial cancer? Dr. Brian Slomovitz: Thanks for that. And as you sort of alluded to, it's been a revolution, really, with immunotherapy. We started off at immunotherapy looking at microsatellite instability or the dMMR patients. What we found is similar to other disease sites in the second and third line setting that we saw good activity with the single agent checkpoints, pembrolizumab dostarlimab, that's based on the earlier KEYNOTE data and the GARNET trial. Really, a landmark study in the second line was Vicki Makker and her colleagues put pembrolizumab and lenvatinib combination for those patients with the cold tumors. Not the dMMRs or MSI Highs, but the proficient mismatch repair. And that study in a second line setting found that it was better than chemotherapy for an overall survival advantage. So right there, we know that it works in the second line setting in the dMMR population, and we got an indication in the PMR population saying that immunotherapy works in all women with endometrial cancer at some point, then we really had the groundbreaking trials. And Shannon, thank you. You are the leader on one of the four trials that happened, to DUO-E, AtTEnd, GY018 and RUBY trial, all very similar studies showing that the combination of immunotherapy with chemotherapy in the first line, metastatic or recurrent setting had a better outcome for patients than if given chemotherapy alone. That actually led to amazing things. We had three of those drugs have FDA approvals, pembrolizumab for all comers, dMMR and PMMR in the first line metastatic setting with chemotherapy; Dostarlimab, PMR, dMMR in the first line or metastatic with chemotherapy. And Shannon, in your study, I think we still have to learn a lot from your study. DUO-E, chemotherapy plus minus dostarlimab. And you also added a PARP inhib, and those patients with a PARP did better. So I'm really looking forward to your data, to the subgroup analysis to figure out which of those patients, depending on the biomarker, do better with PARP therapy. And right now, you have a dMMR FDA indication. But who knows? The future is really exciting to see- to be splitters, not lumpers. And I really want to see how that data pans out. And so that's how it came into the first and second line setting and that led us really to come up with the idea for this trial to put it into the adjuvant setting. Dr. Shannon Westin: Right. And so, I think this would be really important because we're so ingrained in this. We see this on the day to day. Can you kind of tease out a little bit what's different about those patients that would be treated in that advanced recurrent setting versus the patients that would be potentially treated in this B21 study? Dr. Brian Slomovitz: Yeah, so the first step, we demonstrated the efficacy in patients that really the treatment options were an unmet need. In the second line setting, we didn't have good treatment options. Those are the patients with measurable disease, with symptomatic disease giving immunotherapy. And not only did we see the efficacy, which was better, but we also were able to give it with limiting the side effects as seen with chemotherapy, which is nice. And then we know that the first line therapy, traditionally for endometrial cancer with carboplatin paclitaxel, response rates about 50%, progression free survival about a year, really something that we needed to improve upon. So, adding immunotherapy to the platinum backbone therapy really demonstrated an advantage. But now what we want to do is we want to see if we could prevent, in the high-risk patients, those without disease, what can we do to help prevent the disease from recurring and help patients live longer without really the need for really lifesaving types of treatments? We want to prevent it from recurring. Dr. Shannon Westin: Yeah, I think that's essential. We know that if we can sit on that prevention side and kind of invest all the time and effort that we need to upfront, that really does yield the longer survival. So why don't you just walk through the overall design of this trial, please? Dr. Brian Slomovitz: Yeah. So, this was an all-comers trial, meaning in individuals that had high risk endometrial cancer, high risk for recurrence, that included, in endometrial cancer, we have aggressive histologic subtypes, serous histologies, clear cell histologies, any stage, as long as there was some myometrial invasion. We also, for the first time, included patients looking at the molecular subclassifications. So, if there was a P53 mutation and they were stage 1 with myometrial invasion, they were included. And then in all comers, any patients with stage 3 or up to 4a disease, as long as the surgery was for a curative intent, and they had no residual disease after surgery, then they were allowed to enroll into this trial. One of the things is that this is the first time we've done an adjuvant trial this large. I think one of the reasons that helped us succeed in doing a trial like this is that we left radiation as investigator's choice, because a lot of times going into a trial like this, people feel strongly, we know our radiation oncology colleagues, rightfully so, feel that radiation could help prevent disease from coming back. And we also have the camp that says they don't need radiation. We took that question out of this study. We let investigators decide whether or not they're going to get radiation. It was for patients to get chemotherapy, who are going to normally get chemotherapy for their high-risk disease and randomize them to chemotherapy plus placebo or chemotherapy plus pembrolizumab, a PD-1 inhibitor, in order to see if we could prevent the disease from coming back. Dr. Shannon Westin: And the primary results of this study were just presented at ESMO and published in the Annals of Oncology. Can you give us just a quick overview of what that was, what they found? Dr. Brian Slomovitz: Yep. So, we enrolled 1100 patients. The primary objective of the study was to look at the ITT population, progression free survival and overall survival. And the overall study was negative. Okay, so the hazard ratio in the ITT population was 1.02, not demonstrating a benefit of adding pembrolizumab in this population. I would say disappointing, but at the same point, something that we could really learn a lot from and somewhere that we know that in the whole population, we need to come up with better strategies to help prevent recurrence of disease, better adjuvant treatment strategies. But there's also information that we learned from this trial and that we're reporting on that we're actually super excited about and we feel may be game changing. Dr. Shannon Westin: Yeah. So, let's go to that. This is the good news. Your manuscript in the JCO, thank goodness you published it here, was focused on that subset of mismatch repair deficient. So, tell us what you found. Dr. Brian Slomovitz: So, in this study, we found that the first stratification factor was dMMR versus pMMR. Now, in the pMMR group, those patients had further stratification factors, but dMMR by itself was a stratification factor. Amongst those patients that had dMMR tumors, we found the hazard ratio to be 0.31 benefiting those patients who received pembrolizumab in the adjuvant setting. Really something that when we look at the treatment studies, the GY018s, the RUBYs, the atTEnds, the DUO-Es, in a dMMR setting, we see a similar hazard ratio of 0.3, 0.4. But to get that hazard ratio, which was statistically significant, obviously, is something that we were quite pleased with and something that we felt was worthy of reporting further. I will say it was a pre-specified endpoint. We didn't allocate alpha to it. So, at the beginning, it was a pre-specified endpoint, but at the same time even though we didn't specify alpha towards that outcome, it still, we feel is clinically meaningful and can definitely add to affect the standard of care and the management of these patients. Dr. Shannon Westin: Yeah. I'm very intrigued to see what kind of people do with this. It makes sense, mechanistically, it makes sense if there was a population that was going to benefit, if not everybody does, this is the group that will. I mean, do you feel like there's enough data? What are you going to do? FDA approval aside, obviously, those kinds of things. But how do you feel about this? Is this something you're going to offer to your patients? Dr. Brian Slomovitz: The first answer is yes. I think it's something that I would like to offer my patients. As you know, we need one of two things: we either need an FDA approval or for a lot of our payers required to be in the NCCN listings. I don't serve on the committee. I have no influence on NCCN. I'm excited to see how they'll respond to not only the Annals article, but obviously in today's release of the JCO article, I hope that they'll look upon it favorably. It's a drug that we're used to giving. Pembrolizumab, we have a lot of experience with it. It's interesting. We didn't see any new safety signals, Shannon. Dr. Shannon Westin: Yeah, I was going to ask - that's great. Dr. Brian Slomovitz: There was nothing, nothing additional that we found in this trial. So, I feel that it can definitely improve the outcome of those patients, in my view, with high risk for recurrence, treating pembrolizumab in this setting. Dr. Shannon Westin: Yeah, I think it's important, of course, to look at the safety. What about quality of life? Any new findings there? Dr. Brian Slomovitz: Yeah, we did that quality of life as part of the phase 3 trial. No difference between the two arms. No difference between the two arms. When we looked at a couple of the other analyses, we found that the benefit is the same on stage 3, 4 tumors. We saw that the benefit was there as well. So, there were less patients in the stage 1, 2 group. But I think really, for all comers, for the patient population, I would definitely consider giving pembrolizumab, again, for those patients with a deficient mismatch repair. Dr. Shannon Westin: It's really exciting, and I think you mentioned some of the statistical limitations. Anything else that gives you pause about the study or things you wish you did better? I know we always like to armchair quarterback ourselves after we do these kinds of studies. Dr. Brian Slomovitz: Yeah, it's interesting. When we designed the study years ago, we used the best information we had at that time to come up with the study design, and we're happy with it, and we really don't think that we could have done it much better. I should say, this was a great partnership that we had here between the GOG, ENGOT and with sponsor Merck, Toon Van Gorp was the lead PI of the global trial. When he gave me the good opportunity to present it at the IGCS and to be the lead author on this, it was really a great partnership. And when we came up with a trial years ago, it was the best trial that we thought at that time. And based on the information now, I think it's really something that we're excited about these results, even though the overall trial was negative. Dr. Shannon Westin: Yeah, I agree with you. I think it's interesting, it's informative to think about, “Well, what would we do now or then if we knew what we knew now?” But still, you design the trial the best way you can. I think the results are super intriguing. I'm hopeful at the way they'll be reviewed. I agree I don't have any inside information about the NCCN committee, but I do hope that they'll consider the overarching data to support immunotherapy and mismatch repair deficiency and the findings of this study. And then I guess the last question I would just ask, as you're an expert here, what are you looking forward to seeing coming next in this space? What's the stuff you're intrigued about in endometrial cancer? Dr. Brian Slomovitz: I think, Shannon, you and I have talked about this for a while. I think we're getting really close to eliminating chemotherapy for some of the patients who suffer from this disease. So, I'm not sure if we'll do a follow up to this trial, but I think a logical type of follow up would be to see: what if we just took away chemotherapy altogether and we did pembro in the adjuvant setting, pembrolizumab versus chemotherapy? We don't have that trial in the adjuvant setting, but actually, we completed accrual of that trial in the recurrent setting and we're anxiously awaiting those results. That's KEYNOTE-C93, where in the dMMR population we studied pembrolizumab versus carboplatin paclitaxel. How those results may translate into this setting, I'm not sure. Right now, it's exciting what we have, but yeah. And I think future is bright for this. Just to highlight, in the two arms, there's 140 patients approximately in each arm; there were 25 recurrences in those patients who received placebo. Only eight recurrences in those that received pembrolizumab. Really, when we talk about numbers, it's really remarkable and it shows you the benefit it really had on the patients. Dr. Shannon Westin: Well, this was great. It flew by, as it always does when I'm having conversations with you. I just really want to thank you again for taking the time to share your knowledge with our listeners. Dr. Brian Slomovitz: Thanks, Shannon. Dr. Shannon Westin: And listeners. Thank you all for taking the time to hear about endometrial cancer. Again, this was “Pembrolizumab or Placebo, Plus Adjuvant Chemotherapy, With or Without Radiotherapy for Newly Diagnosed High Risk Endometrial Cancer Results in Mismatch Repair Deficient Tumors.” And this was the JCO After Hours. If you loved what you heard, please check out wherever you get your podcast to see what else we have to offer. Have an awesome day. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

New Advances in Bladder Cancer Treatment: What You Need to Know

Bladder Cancer Matters

Play Episode Listen Later Oct 10, 2024 33:05

In this informative episode of Bladder Cancer Matters, host Rick Bangs welcomes back Dr. Ashish Kamat, an expert in urology and bladder cancer research from MD Anderson Cancer Center. They dive into the latest updates on BCG (Bacillus Calmette-Guérin) and its crucial role in treating non-muscle invasive bladder cancer. Dr. Kamat provides an insightful overview of BCG's effectiveness, the current shortage, and emerging alternatives. He explains the factors behind the supply issues and how treatments such as reduced dosages and novel combinations like gemcitabine and docetaxel are helping to bridge the gap. Listeners will also hear about promising new therapies on the horizon, including gene therapy with Adstiladrin, Pembrolizumab, and ANKTIVA's combination with BCG. Dr. Kamat sheds light on how these advancements could change the landscape of bladder cancer treatment while emphasizing the importance of tailored care and shared decision-making for each patient. This episode is a must-listen for those affected by bladder cancer and anyone interested in the latest medical developments in this field.

GI Cancer ESMO 2024 Highlights: Key Studies Discussed LEAP-012, KEYNOTE-811, POD1UM-303, NICHE-2

Play Episode Listen Later Oct 10, 2024 15:06

Join us in this exciting episode of the Oncology Brothers podcast as we dive into the highlights from ESMO 2024, focusing on gastrointestinal malignancies. Hosts Drs. Rohit and Rahul Gosain are joined by Dr. Kristen Ciombor, a GI medical oncologist from Vanderbilt University, to discuss four key studies that have significant implications for clinical practice. In this episode, we covered: •⁠ ⁠LEAP-012 Study: An update on HCC treatment with Lenvatinib and Pembrolizumab combined with TACE, exploring the promising progression-free survival (PFS) data and the need for mature overall survival (OS) results. •⁠ ⁠Keynote-811: The current standard of care for HER2-positive gastroesophageal junction and gastric adenocarcinoma, highlighting improved OS with Pembrolizumab, chemotherapy, and Trastuzumab. •⁠ ⁠POD1UM-303 Trial: A groundbreaking study in metastatic anal cancer that shows significant OS improvement with the addition of the PD-1 inhibitor Retifanlimab to chemotherapy. •⁠ ⁠NICHE-2 Study: A remarkable update on MSI-high patients, showcasing a 100% three-year disease-free survival rate with neoadjuvant immunotherapy. Tune in for an insightful discussion that will keep you updated on the latest advancements in GI oncology! Don't forget to like, subscribe, and hit the notification bell for more conference highlights and oncology discussions. #OncologyBrothers #ESMO24 #GIMalignancies #CancerResearch #Podcast Subscribe for more updates and insights from the Oncology Brothers! Website: http://www.oncbrothers.com/ Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

cancer os studies leap niche keynote gi discussed pd vanderbilt university rohit msi hcc her2 pfs esmo tace pembrolizumab trastuzumab lenvatinib kristen ciombor

ESMO 2024 Congress Highlights in Gynecologic Cancer: New Data Informing Treatment of Ovarian, Endometrial, and Cervical Cancers

CCO Oncology Podcast

Play Episode Listen Later Oct 1, 2024 30:45

In this episode, listen to Ana Oaknin, MD, PhD and Alexandra Leary, MD, PhD, share their clinical insights and takeaways on key updates and new data presented for ovarian, endometrial, and cervical cancer at the ESMO 2024 annual congress including:Phase III PRIMA/ENGOT-OV26/GOG-3012 Final OS Results: Niraparib as First-Line Maintenance in Advanced Ovarian CancerATHENA COMBO/GOG-3020/ENGOT-ov45: Rucaparib With or Without Nivolumab Maintenance in Newly Diagnosed Ovarian CancerPhase II PICCOLO Trial of Mirvetuximab Soravtansine in Recurrent Platinum-Sensitive Ovarian Cancer With High-FRα ExpressionPhase III KEYNOTE-B21/GOG-3053 Study of Adjuvant Chemotherapy With or Without Radiotherapy With or Without Pembrolizumab in Patients With Newly Diagnosed Endometrial Cancer or Carcinosarcoma After Curative Surgery With no Residual DiseasePhase III KEYNOTE-A18 Overall Survival Results: Pembrolizumab Plus Concurrent Chemoradiation in High-Risk Locally Advanced Cervical Cancer Program faculty:Ana Oaknin, MD, PhDHead of Gynaecologic Cancer ProgrammeDepartment of Medical OncologyVall d' Hebron University HospitalVall d'Hebron Institute of Oncology Barcelona, SpainAlexandra Leary, MD, PhDCo-Director, Department of Medical OncologyMedical Oncologist, GynecologyTeam Leader, Gynecologic Translational Research Lab, Institut Gustave RoussyParis, FranceResources:To download the slides associated with this podcast discussion, please visit the program page.

phd study congress md treatments prima immunotherapy cervical new data ovarian cancer cervical cancer informing ovarian endometrial esmo pembrolizumab gynecologic cancers nivolumab dmmr dostarlimab engot

WCLC 2024 Highlights - Exploring Latest Advances in Lung Cancer Treatment

chief treatments drs pd rahul checkmate lung cancer medical oncology world conference vegf latest advances pembrolizumab lung cancer treatment sylvester comprehensive cancer center wclc

Play Episode Listen Later Sep 19, 2024 20:24

Welcome to the Oncology Brothers podcast! In this episode, hosts Drs. Rahul and Rohit Gosain are joined by Dr. Gilberto Lopes, Chief of Medical Oncology at the Sylvester Comprehensive Cancer Center, to discuss the highlights from the World Conference on Lung Cancer 2024. Join us as we dive into four key studies that could reshape our understanding and approach to lung cancer treatment: 1. Checkmate 816 vs. Checkmate 77T: An exploratory analysis of neoadjuvant chemoimmunotherapy and the ongoing debate about the benefits of post-operative immunotherapy. 2. SKIPPirr Study: Discover how prophylactic strategies can reduce infusion-related reactions with amivantamab. 3. HARMONi-2: A look at a novel PD-1 and VEGF inhibitor compared to Pembrolizumab in metastatic non-small cell lung cancer. 4. TROPION-Lung01: Insights into the performance of the antibody-drug conjugate Dato-DXd against docetaxel, particularly in non-squamous histology. Tune in for an informative discussion that highlights the latest advancements in lung cancer research and treatment strategies. Don't forget to like, subscribe, and check out our other episodes for more insights into the current standard of care in oncology! #OncologyBrothers #LungCancer #WCLC2024 #CancerResearch #MedicalOncology Website: http://www.oncbrothers.com/ Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

FDA Approval: KEYNOTE 483, Pembrolizumab plus Chemotherapy for Mesothelioma

Lung Cancer Considered

Play Episode Listen Later Sep 18, 2024 22:39

In a special episode of Lung Cancer Considered, host Dr. Stephen Liu discuss the recent FDA approval of pembrolizumab plus platinum and pemetrexed for mesothelioma, based on the phase III KEYNOTE 483 study. Guest: Dr. Ibiayi Dagogo-Jack is a thoracic oncologist from Massachusetts General Hospital and Assistant Professor at Harvard Medical School Guest: Dr. Quincy Chu is a thoracic oncologist at the University of Alberta Cross Cancer Institute's New Drug Development Program and CCTG Investigational New Drug Committee Chair

university fda assistant professor keynote massachusetts general hospital chemotherapy fda approval mesothelioma pembrolizumab ibiayi dagogo jack

NEJM at ESMO — Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma

New England Journal of Medicine Interviews

Play Episode Listen Later Sep 14, 2024 3:11

Did you miss the ESMO Congress 2024? Listen here: NEJM Editor-in-Chief Eric Rubin and NEJM Evidence Associate Editor Oladapo Yeku discuss research that was presented at the 2024 European Society of Medical Oncology annual meeting. Visit NEJM.org to read the latest research.

doctors medicine physicians muscle observation oncology invasive hematology european society nejm carcinoma medical oncology adjuvant esmo pembrolizumab

NEJM at ESMO — Overall Survival with Pembrolizumab in Early-Stage Triple- Negative Breast Cancer

New England Journal of Medicine Interviews

Play Episode Listen Later Sep 14, 2024 3:23

doctors medicine survival physicians breast cancer oncology early stage hematology european society nejm medical oncology triple negative breast cancer esmo pembrolizumab

NEJM at ESMO — Pembrolizumab in HER2+ Gastric Cancer

New England Journal of Medicine Interviews

Play Episode Listen Later Sep 13, 2024 2:21

doctors medicine physicians oncology gastroenterology hematology european society nejm her2 medical oncology esmo gastric cancer pembrolizumab

Midyear Highlights of Key Data From 2024 Gynecologic Cancer Conferences Informing Treatment of Ovarian, Endometrial, and Cervical Cancers

CCO Oncology Podcast

Play Episode Listen Later Aug 5, 2024 49:32

In this episode, listen to Floor J. Backes, MD, and Angeles Alvarez Secord, MD, MHSc, share their clinical insights and takeaways on new data presented for endometrial, ovarian, and cervical cancers presented at the 2024 annual meetings of the Society of Gynecologic Oncology and American Society of Clinical Oncology including:RUBY Part 1 Subgroup Analyses by MRR Status: Addition of dostarlimab to platinum-based therapy followed by dostarlimab maintenance in advanced endometrial cancerRUBY Part 2: Survival outcomes with addition of dostarlimab to platinum-based therapy followed by dostarlimab plus niraparib maintenance in advanced endometrial cancerSurvival Analyses From Phase III NRG GY018: Carboplatin plus paclitaxel with or without pembrolizumab as frontline treatment for patients with advanced endometrial cancerDUO-E: First-line therapy with carboplatin plus paclitaxel plus bevacizumab and durvalumab followed by maintenance with bevacizumab, durvalumab, and olaparib in newly diagnosed endometrial cancerLong-term Follow-up From SIENDO: PFS in TP53 wild-type and preliminary survival by molecular subgroups in patients with endometrial cancer and complete or partial response after ≥12 weeks of first line taxane/carboplatinSubgroup Analyses From the Randomized Phase III MIRASOL: Mirvetuximab soravtansine vs investigator's choice of chemotherapy in FR

Efficacy of Pembrolizumab with sEphB4-HSA in HPV-negative EphrinB2-positive HNSCC

Oncotarget

Play Episode Listen Later Jul 22, 2024 3:21

BUFFALO, NY- July 22, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on July 10, 2024, entitled, “Improved efficacy of pembrolizumab combined with soluble EphB4-albumin in HPV-negative EphrinB2 positive head neck squamous cell carcinoma.” Patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) after primary local therapy have low response rates with cetuximab, systemic chemotherapy or check point inhibitor therapy. Novel combination therapies with the potential to improve outcomes for patients with HNSCC is an area of high unmet need. In this new study, researchers Alexandra Jackovich, Barbara J. Gitlitz, Justin Wayne Wong Tiu-lim, Vinay Duddalwar, Kevin George King, Anthony B. El-Khoueiry, Jacob Stephen Thomas, Denice Tsao-Wei, David I. Quinn, Parkash S. Gill, and Jorge J. Nieva from Rutgers New Jersey Medical School and the University of Southern California conducted a phase II single-arm clinical trial of locally advanced or metastatic HNSCC patients treated with a combination of soluble EphB4-human serum albumin (sEphB4-HSA) fusion protein and pembrolizumab after platinum-based chemotherapy with up to 2 prior lines of treatment. “sEphB4-HSA in combination with pembrolizumab has a safety profile similar to what has been observed previously with no overlapping toxicity.” The primary endpoints were safety and tolerability and the primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). HPV status and EphrinB2 expression were evaluated for outcome. Twenty-five patients were enrolled. Median follow up was 40.4 months (range 9.8 – 40.4). There were 6 responders (ORR 24%). There were 5 responders in the 11 HPV-negative and EphrinB2 positive patients, (ORR 45%) with 2 of these patients achieving a complete response (CR). The median PFS in HPV-negative/EphrinB2 positive patients was 3.2 months (95% CI 1.1, 7.3). Median OS in HPV-negative/EphrinB2 positive patients was 10.9 months (95% CI 2.0, 13.7). Hypertension, transaminitis and fatigue were the most common toxicities. “The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC.” DOI - https://doi.org/10.18632/oncotarget.28605 Correspondence to - Alexandra Jackovich - atj41@njms.rutgers.edu, and Jorge J. Nieva - jorge.nieva@med.usc.edu Video short - https://www.youtube.com/watch?v=8SVmHYQigwA Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28605 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, EphrinB2, EphB4, HNSCC, pembrolizumab, HPV-negative About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Ep. 178 ASCO 2024: Game-Changing GU Oncology Updates in Bladder and Kidney Cancers with Dr. Sumanta Pal and Dr. Petros Grivas

BackTable Urology

Play Episode Listen Later Jul 16, 2024 56:23

Stay up-to-date on the latest advancements and treatment strategies in the field of genitourinary oncology. In this episode of BackTable Urology, guest host Dr. Bogdana Schmidt, a urologic oncologist from the University of Utah, discusses takeaways from ASCO 2024 with Dr. Petros Grivas from Fred Hutchinson Cancer Center and Dr. Sumanta (Monty) Pal from City of Hope. --- CHECK OUT OUR SPONSOR Siemens Healthineers Theranostics https://www.siemens-healthineers.com/en-us/clinical-specialities/theranostics --- SYNPOSIS The conversation initially focuses on advanced urothelial carcinoma and the EV302 trial, discussing detailed insights from the quality-of-life results presented at ASCO. The experts offer relevant clinical perspectives for modern metastatic urothelial carcinoma management, focusing on pembrolizumab plus enfortumab vedotin. Further, they delve into breaking biomarker research at ASCO, including KIM-1 in adjuvant renal cell carcinoma (RCC) therapy and the HIF-2 inhibitor DFF332 for chromophobe RCC. --- TIMESTAMPS 00:00 - Introduction 03:42 - Pembrolizumab and Enfortumab Vedotin Trial Insights 07:43 - Future Trials and Treatment Strategies 21:27 - Javelin Bladder 100 Trial Discussion 32:05 - Growth Factor Use 36:21 - Future Directions of Biomarkers 38:55 - Kidney Cancer Biomarker Trials 53:40 - Concluding Thoughts

university cancer utah game changing kidney oncology bladder concluding thoughts asco future directions petros rcc hif pembrolizumab sumanta sumanta monty pal

KEYNOTE A18-Addition of Pembrolizumab to Chemoradiation in Cervical Cancer with Domenica Lorusso

IJGC Podcast

Play Episode Listen Later Jun 17, 2024 28:51

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Dr. Domenica Lorusso to discuss the KEYNOTE A18 clinical trial. Dr. Domenica Lorusso, MD, PhD, directs the Gynaecological Oncology Unit at Humanitas Hospital, Milan, and holds a Full Professorship in Obstetrics and Gynaecology at Humanitas University, Rozzano, Milan. She has led/participated in approximately 250 phase I-IV clinical trials. Currently overseeing more than 60 studies as Principal Investigator, Dr. Lorusso also chairs the Clinical Trials Committee of the MITO Group. She serves on the Board of Directors of the GCIG and is an active member of ENGOT, where she chairs the Gynecological Cancer Academy. Additionally, she sits on the Board of Directors of the ESGO. With around 300 international oncology publications and contributions to national and international treatment guidelines, her primary objectives are to ensure optimal patient care, foster clinical research, and advance international collaborations and education in the field. Highlights: - Concurrent chemoradiation plus brachiterapy represent the standard of care treatment in locally advanced cervical cancer providing up to 70% 5 years OS - Modern radiotherapy technique (IMRT and VMAT) has reported to further increase OS and reduce toxicity - Immunotherapy has reported to increase OS in advanced or recurrent cervical cancer when compared to standard treatment - Immunotherapy in combination with concurrent high quality chemoradiation in the treatment of locally advanced high risk cervical cancer further increase PFS and OS with respect to standard chemoradiotherapy and should be considered the new standard of care - The combination appears manageable and no substanciad additional toxicity has been reported

director phd board md os keynote addition obstetrics principal investigators immunotherapy domenica cervical cancer gynaecology pfs lorusso pembrolizumab rozzano editor in chief dr imrt chemoradiation humanitas university engot vmat

S10 Ep33: Park and Sonpavde on Considerations for Enfortumab Vedotin Plus Pembrolizumab in Bladder Cancer

Play Episode Listen Later May 30, 2024 10:27

Drs Park and Sonpavde emphasize their insights on the topline data from the EV-302 trial, considerations for community oncologists when deciding whether to prescribe enfortumab vedotin plus pembrolizumab to patients with urothelial carcinoma, their advice for monitoring and managing treatment-related toxicities with this combination, and more.

park considerations ev bladder cancer pembrolizumab sonpavde

Specialist Spotlight: Urothelial Carcinoma Update From the ASCO GU Symposium 2024

specialist drs symposium uc dana farber cancer institute carcinoma bladder cancer jonathan rosenberg pembrolizumab histopathology asco gu

Play Episode Listen Later May 17, 2024 10:55

Drs. Alicia Morgans and Jonathan Rosenberg share their insights into some interesting abstracts from the 2024 ASCO GU symposium: one covering a model to help predict response to neoadjuvant chemotherapy in patients with muscle invasive UC, and another regarding results from the PemCab study of pembrolizumab and cabozantinib in first‑line advanced UC.

ASCO Genitourinary Symposium 2024: Late‑Breaking Presentations on EV‑302 and AMBASSADOR

san francisco ambassadors ev drs symposium presentations asco dana farber cancer institute bladder cancer genitourinary jonathan rosenberg pembrolizumab asco gu

Play Episode Listen Later May 16, 2024 10:14

Drs. Jonathan Rosenberg and Alicia Morgans share their insights into some late-breaker abstracts presented at the 2024 ASCO GU symposium in San Francisco. The first is a subgroup analysis from EV‑302 with enfortumab vedotin and pembrolizumab, and the other is AMBASSADOR, which looks at adjuvant pembrolizumab in locally advanced and muscle invasive urothelial cancer.

Specialist Spotlight: Advanced Urothelial Carcinoma: Considerations in Therapeutic Sequencing

specialist considerations drs therapeutic sequencing her2 carcinoma bladder cancer adcs jonathan rosenberg pembrolizumab nivolumab

Play Episode Listen Later May 15, 2024 10:55

Drs. Alicia Morgans and Jonathan Rosenberg share their insights into therapeutic sequencing in patients with advanced urothelial cancer, reviewing patient selection and timing, options following progression on immunotherapy, and future therapeutic agents such as HER2‑targeted ADCs.

Specialist Spotlight: Neoadjuvant Approach to Urothelial Carcinoma: Treatment With Curative Intent

treatments specialist intent drs rosenberg morgans carcinoma bladder cancer adcs curative neoadjuvant pembrolizumab antibody drug conjugates

Play Episode Listen Later May 13, 2024 13:09

Drs. Rosenberg and Morgans share their insights into neoadjuvant therapy in the management of patients with muscle invasive urothelial carcinoma, including patient‑ and treatment‑related factors that may influence decision making, bladder‑preservation, and the future of neoadjuvant therapy with immunotherapy and ADCs.

Breakthrough in Bladder Cancer: FDA approval - Enfortumab Vedotin + Pelbrolizumab with Dr. Tom Powles

discover breakthrough drs rahul fda approval bladder cancer pembrolizumab ctdna

Play Episode Listen Later Mar 27, 2024 18:35

Join the Oncology Brothers, Drs. Rahul and Rohit Gosain, as they dive deep into the groundbreaking EV302 study with special guest Dr. Thomas Powles. In this episode, they discuss the approval of Enfortumab and Pembrolizumab as a combination therapy for advanced bladder cancer, based on the remarkable results of the study. Dr. Powles shares insights on the study design, findings, and the transformative impact of the treatment on patients' lives. Discover how this new standard of care in bladder cancer has significantly improved overall survival benefits, with a median survival of 31.5 months compared to 16.1 months with chemotherapy. The discussion also delves into managing the side effects of the treatment and the potential use of ctDNA in monitoring disease progression. Don't miss this informative episode that sheds light on the evolving landscape of bladder cancer treatment and the hope it brings to patients. Stay tuned for a quick recap and insights from the Oncology Brothers.

Baby loss certificates, 'Women's intuition', Carolynne Hunter & energy bills

Woman's Hour

Play Episode Listen Later Mar 20, 2024 57:25

On 27 February, Emma Barnett spoke to Zoe Clark-Coates, who runs the baby loss and bereavement charity The Mariposa Trust, about her campaign for baby loss certificates. They were introduced in England in February for parents who've lost a baby before 24 weeks of pregnancy. Emma shares her own story and also speaks to a woman who's decided it's not for her, and another who applied straight away and has now received four baby loss certificates. Have you ever had a nagging feeling that something wasn't quite right? A gut reaction or a tingly spidey-like sense that tells you something is off? Author of Emotional Labour, Rose Hackman joins Emma to explain why we need to stop calling it 'women's intuition'. Carolynne Hunter cares for her 14-year-old daughter who has severe cerebral palsy. She spoke out about her rising household costs back in 2022 and Oscar-winning actress Kate Winslet paid her energy bill. Carolynne joins Emma to give an update on her life since then. It's been announced that a breast cancer drug - Pembrolizumab, sold under the brand name Keytruda - could help thousands more women than previously thought. Emma finds out more from Dr Liz O'Riordan, retired breast surgeon who has had breast cancer herself, twice.Presented by Emma Barnett Producer Louise Corley Studio Engineer: Phil Lander

babies england energy loss intuition bills certificates kate winslet keytruda emotional labour emma barnett pembrolizumab carolynne

Pembrolizumab in Patients With Advanced Cancers With HTMB

Play Episode Listen Later Mar 14, 2024 19:56

Dr. Shannon Westin and her guests, Dr. Herbert Duvivier and Dr. Richard Schilsky, discuss the paper “Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry Study” published in the JCO. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in-depth into articles published in the Journal of Clinical Oncology. I am your host, Shannon Westin, GYN Oncologist and Social Media Editor of the JCO. As always, it is my pleasure to serve and bring this information to you. Today, we will be discussing, “Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry Study.” And this was published in the JCO on August 10th, 2023. None of the authors have any conflicts of interest to disclose. Joining me today are two of the authors, Dr. Herbert Duvivier, the principal investigator of this arm of the TAPUR trial. Welcome. Dr. Herbert Duvivier: Thank you. Shannon Westin: And then, of course, many of you know Dr. Richard Schilsky, who is the former CMO and Executive Vice President of ASCO and a principal investigator on the TAPUR study. Dr. Richard Schilsky: Thank you, Shannon. Shannon Westin: So, let's get going. I think the first thing would be great is to level set and make sure everyone knows exactly what this TAPUR basket trial is, the Targeted Agent and Profiling Utilization Registry study. Can you guys give the audience a brief description of the objective of TAPUR and maybe how it came to fruition? Dr. Richard Schilsky: Sure. This is Richard Schilsky. Maybe I can start with that. The TAPUR study is a prospective, phase II, multi-basket, multi-center genomic-matching trial. Its primary objective is to identify signals of drug activity for targeted agents that are already marketed. But in the TAPUR study they are being used outside of their FDA-approved indication. The study, as you may know, was conceived in 2014, launched in 2016, and is still enrolling patients across the country. Really, the genesis of the study came from the fact that it began at the time where genomic profiling of patients with advanced cancer was becoming more commonplace. Genomic alterations that could be targeted by already marketed drugs were being identified. However, patients and doctors were having difficulty accessing these drugs because they were not used on label and were unlikely to be covered by insurance. And moreover, even if they could access the drugs, there was no organized mechanism to collect outcome data and report on the results of the patient experience receiving that treatment. So those factors led to the development of TAPUR, which attempts to solve both the drug access problem by having collaborating pharmaceutical companies donate their drugs to the trial so they're available to patients at no cost, but also implements a structured data collection mechanism so all of the relevant clinical outcomes with the patients can be collected and ultimately reported. And that's how TAPUR came about. Shannon Westin: Well, it was so necessary, and I think we do so much of our oncology treatments off-label, but as we get more and more expensive drugs when we move away from chemotherapies and more targeted immunotherapies, it's very hard to get those drugs off label. So this was such a relevant and necessary trial that had to happen, and it's a great example of leadership that you had the vision to put this together through ASCO. I think the natural next question for me is having not put patients on the TAPUR study, how does a patient join this study? How do they get started? Walk us through that. Dr. Herbert Duvivier: At our institution, normally, all the physicians are aware of the TAPUR trial through internal conversations. When they have patients who have been treated with multiple lines of standard therapy, usually the next step for them is to get NGS testing. We have a research team that reviews all NGS testing for these patients and knows the open arms of the TAPUR trial. And if there happens to be a particular patient who may match with one, they will inform the physician. It is then up to the physician to speak to the patient about that option. Shannon Westin: Do you have people come looking for the TAPUR trial or are these generally more established patients? Dr. Herbert Duvivier: From my perspective, I think it is usually established patients. Shannon Westin: I think what I love about this trial, and I have spoken about this trial in lectures around baskets, it's such a pragmatic design making it as straightforward as possible to really implement across different centers, whether academic or community, or wherever they are. I guess one of the questions always around these targeted therapies is the molecular selection. How do you make sure that people are being appropriately molecularly selected and how do you decide which testing to utilize? Dr. Richard Schilsky: As you pointed out, Dr. Westin, the goal of the study from the beginning was to have a very pragmatic design, in a sense to have this study attempt to replicate the way oncologists were deploying precision medicine in their practice. The study has broad eligibility criteria, it has minimum necessary data collection, it uses conventional clinical evaluations, there are no additional clinical evaluations required that are not part of routine clinical care. And it just makes it easy to embed the study into the clinical workflow. The study is based largely at community sites, about 85% of the 268 participating sites are located in smaller communities. The study has a set of genomic matching rules that are listed in the protocol and baked into the IT platform for the study as a rules engine. For every treatment available in TAPUR, there is a set of genomic inclusion and exclusion criteria. So in essence the way it works, the physician determines that NGS testing is appropriate for their patient and can use any NGS test they want, as long as the test is performed in a CLIA certified, CAP, or New York State-accredited laboratory. They select the test, they select the biospecimen to be tested, they get the results, they look at the results, and they determine if there is a genomic alteration in the patient's tumor that is targeted by one of the study treatments in the TAPUR study. They can enter that into the rules engine, the rules engine will confirm or not that the appropriate alteration of treatment has been selected. If it is confirmed, then the patient can immediately be enrolled in the study if they meet the clinical inclusion and exclusion criteria. If the rules engine does not confirm the treatment match is appropriate, or in some cases there are multiple possible treatment matches, if there are multiple alterations that can be targeted, or another case is the doctor is simply uncertain about which alteration is best to target, then the clinical site can send that patient case to the TAPUR molecular tumor board. A group of experts convenes weekly that reviews the clinical history, the pathology report, genomic test report, the prior therapy the patient has received, and they make a determination as to whether or not there is an appropriate therapy that's available on TAPUR for the patient. And if not, then are there other potential therapies that are available that could be considered. That information is sent back to the treating physician who determines whether or not here she feels that treatment option is appropriate for their patient, and if so, the patient can then be enrolled and receive the therapy. Shannon Westin: So awesome. I love the idea. If we don't have an arm for you on our trial, we can help assist you potentially determine an option for your patient outside of that. That's so clever. Okay. So let's get into this particular arm. Obviously, our audience is quite savvy and are aware of the role of immune checkpoint inhibition across a number of solid tumors. Could you describe what you sought to determine in this particular arm of the TAPUR study? Dr. Herbert Duvivier: I think one of the most important things to remember about this study is that this study was opened and accruing prior to pembrolizumab becoming FDA approved in, I think, June of 2020. So prior to June of 2020, there was no indication for pembrolizumab in high TMB tumor types and the goal of the study was to determine if pembrolizumab had any overall response rate, duration of responses, progression-free survival, or overall survival advantage over what would be considered standard chemotherapy at that time in patients with high TMB. Dr. Richard Schilsky: Yeah, that's exactly right. And in this paper that we're discussing, we're reporting on two different groups of patients. So there's a group of 28 patients, all with colorectal cancer, all of whom had high tumor mutation burden, as defined by the protocol. And that's one group. Then there's a second, larger group of patients, which is a very heterogeneous group of solid tumor patients. And the reason that that group is reported is there were patients who were being enrolled with multiple different tumor types with high tumor mutation burden. Each tumor type determined a specific, tumor-specific cohort in the study, and they were enrolling at different rates depending upon how common the particular tumor type was. But once the FDA approval for pembrolizumab, for any tumor with a high tumor mutation burden, was granted, then all of those cohorts essentially had to close to new enrollments because there was no longer an off-label use for pembrolizumab in that setting - everything was now on the label. The result was that we then basically collapsed all of the open cohorts that were not then going to be able to complete into this one large, heterogeneous cohort that's being reported in this paper. And going back to the colorectal results, in the paper, we describe a disease control rate of 31%, an objective response rate of 11%. There were three patients who had partial responses lasting 12, 27, and 97 weeks each. And I think it's important to point out that in this particular cohort, essentially all of the colon cancer patients were microsatellite stable. So that's an interesting nuance here because we know that pembrolizumab is active and has an FDA approval in microsatellite high tumors. But this particular group of patients was essentially all microsatellite stable, suggesting that even in that population, if the tumor also has a high tumor mutation burden, the patient has the potential to respond and benefit from the treatment. Shannon Westin: I found that very intriguing. And, of course, as a gynecologic oncologist that treats endometrial cancer, I'm always thinking about MSI and microsatellite stability. So I was very intrigued by this. We are not seeing a ton of TMB high in our population, but there are some patients that do have that. So let's talk a little bit about the results for the collapsed all solid tumor group. What did you find there? Dr. Herbert Duvivier: In the histology pool cohort, there were 47 patients representing 21 different tumor types, with a median tumor mutational burden of approximately 13 mutations per megabase with a range of 9 to 228. 40 of 47 patients had MSS disease, microsatellite stable disease. 6 of the 47, MSS was not reported, and 1 case was ambiguous. The disease control rate was about 45%, and the objective response rate was 26%. There were 3 complete responses: 1 in bladder, 1 in parotid, and 1 in squamous cell carcinoma. 9 partial responses and 9 stable disease 16 plus weeks. Of interest in the patients that were responding, 10 out of the 21 patients had POLE or POLD1 mutations, and 9 of the 21 patients had BRCA1 or BRCA2 mutations, although most of those mutations were classified as variants of uncertain significance. Shannon Westin: That's really interesting. We've seen pretty good data for POLE and benefit from immunotherapy, although at least in the GYN tumors and especially in endometrial cancer, those patients usually do well no matter what you do with them. And so they don't often make it to get immunotherapy because they have a complete response up front to their surgeries. So very intriguing to see that driving benefit. I'm just interested to see because it seems like there's a range that you were quoting of what was considered to be TMB high. So did you see a correlation for response to therapy based on how high the tumor mutational burden was in a given tumor or tumor type? Dr. Herbert Duvivier: Yes, actually we did see a moderately negative correlation between maximum percent change from baseline in a tumor and increasing TMB, which indicated an association between a higher TMB and greater shrinkage of tumor lesions. Dr. Richard Schilsky: I should point out, by the way, that when we introduced this arm into the TAPUR study, this high tumor mutation burden arm, as Dr. Duvivier has already pointed out, it was prior to, of course, the FDA approval, and the FDA approval is for tumors that have at least 10 mutations per megabase. It was also prior to the adoption of that threshold of 10, based on work by Friends of Cancer Research and others as sort of the convention for what defined a high tumor mutation burden. So when we put this into TAPUR, we essentially consulted with some of the testing laboratories. We consulted with Merck, the sponsor for pembrolizumab and actually in the TAPUR study, we defined a threshold of 9 mutations per megabase as defining high tumor mutation burden. Now, as Dr. Duvivier said, there's a broad range of tumor mutation burden represented in this population, and there does seem, if you look at, if the readers want to look at figure 4 in our paper, there does seem to be a general correlation between best response and number of mutations per megabase, which also holds true in a modest way for both progression-free and overall survival. So, TMB is somewhat predictive of favorable outcomes. It's not a perfect biomarker by any means, but generally speaking, if you have enough patients, you can define this sort of trend to support the notion that the more mutations, the greater the likelihood of benefit. Shannon Westin: That makes a lot of sense. One other thing that I just wanted to comment on before we kind of bring the podcast to a close is I was really struck by the high proportion of underrepresented minorities in this arm of TAPUR, and I just would love to hear your thoughts on how the design improves recruiting in this population of patients. Dr. Richard Schilsky: This was a goal of the study, very intentional. When you look at the overall study demographics, there are about 2800 patients now that have been enrolled on TAPUR overall. Almost 12% are black, about 6% are Hispanic, about 4% Asian. The median age is about 64. So it's a slightly older population. The goal always was to enroll a population of patients in TAPUR that was broadly representative of the patients that oncologists treat in practice. In the way we accomplished what we've accomplished, we still have work we can do to improve it. But the clinical sites were carefully selected and vetted. We focused on sites that served a significant fraction of minority patients. We made the eligibility criteria simple and broad, so many of the eligibility criteria that might typically exclude minority populations or older patients from clinical trials are not exclusion criteria in TAPUR. We made the operations of the trial simple, so patients really aren't asked to do much more than what they would normally be asked to do in the course of their routine cancer care. So I think all of those things together have made it possible to attract and enroll a more representative patient population in the study. And we're very gratified by that because when you look at many of the registration trials for many cancer drugs, minorities and older people are terribly underrepresented. So we feel that TAPUR is adding value there and adding useful information. Shannon Westin: I think it's so generalizable and really the way people are practicing, and so to see similar results or concordant results, despite not as much of the rigorous testing and potentially exclusion of certain patient populations is really reassuring and certainly very exciting. The last question is what's coming next? What other arms are coming soon? And can sites still join? Is this something where it's ongoing enrollment and participation? Dr. Richard Schilsky: So sites can still join. There's a place on the ASCO website where sites can find more information about TAPUR, and there's essentially a form available where sites can indicate their interest in joining the study. And then those sites are then evaluated by the TAPUR study team to determine if they meet the minimum necessary requirements to qualify to join the study. There's a lot more data coming out, many more papers that are in press and being written. There are two abstracts that will be presented in April at the AACR meeting. There are three abstracts that have been submitted for the ASCO annual meeting. So a lot more data to come. This is a study that, at least hypothetically, could continue in perpetuity as long as we're able to continue to attract new drugs and new treatment combinations onto the TAPUR study platform. So the TAPUR team is always on the lookout for drugs that are about to get an FDA approval and that could be appropriate for the TAPUR study and continue to talk to many pharmaceutical companies about their interest in potentially putting their drugs on the platform. Shannon Westin: Well, great. Thank you both for taking the time. I know you're both incredibly busy. Again, this has been “Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry Study.” I'm your host, Shannon Westin, and I'm so grateful that you joined us on JCO After Hours. Please check out our other offerings on the website or wherever you get your podcasts. Have an awesome day. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Duvivier's COIs: Speakers' Bureau Company name: Guardant Health Company name: AstraZeneca Company name: Regeneron Schilsky's COIs: Leadership Company name: Clarified Precision Medicine Company name: Leap Therapeutics Stock and Other Ownership Interests Company name: EQRx Company name: Leap Therapeutics Consulting or Advisory Role Company name: Cellworks Company name: Scandion Oncology Company name: Bryologyx Company name: Illumina Company name: EQRx Company name: Syapse Company name: Zephyr AI Company name: AADi Research Funding Company name: AstraZeneca Company name: Bayer Company name: Bristol-Myers Squibb Company name: Genentech/Roche Company name: Lilly Company name: Merck

friends walk cancer asian journal patients fda cap cmo hispanic new york state pole merck cancer research asco gyn msi genomic brca1 mss clinical oncology ngs brca2 clia tmb duvivier aacr jco social media editor pembrolizumab bristol myers squibb company

Ep. 423 Next Level Electroporation Therapy: The RadioClash Story with Dr. John Qiao

BackTable Podcast

Play Episode Listen Later Mar 8, 2024 50:50

In this episode of the BackTable Podcast, host Dr. Aaron Fritts interviews guest Dr. John Qiao about exploration of physicians' role in medical innovation, particularly among interventional radiologists. Dr. Qiao shares insightful information about the origin of RadioClash and details his journey as an entrepreneur. Through this discussion, Dr. Qiao covers the challenges encountered during the startup phase, the invention of a single-probe electroporation device, and the future applications of this novel medical technology. The episode concludes with broader advice on how to manage the demands of professional work, entrepreneurship, and personal life. --- CHECK OUT OUR SPONSORS Reflow Medical https://www.reflowmedical.com/ Medtronic Concerto https://mobile.twitter.com/mdtvascular --- SHOW NOTES 00:00 - Introduction 02:39 - Dr. Qiao's Journey into Medicine and Entrepreneurship 11:40 - Birth of Radioclash: A Unique Solution for Cancer Treatment 17:58 - Future of RadioClash: Targeting Metastatic Cancer 25:20 - Future of Electroporation Therapy 35:21 - Challenges of Building a Company 44:37 - Path to Market and Future Plans 47:28 - Balancing Clinical Practice and Entrepreneurship --- RESOURCES RadioClash website: https://www.radioclash.co/ News Article on Dr. John Qiao: https://voyagehouston.com/interview/meet-john-qiao-m-d-of-radioclash-ltd-co/ Radiation Therapy as a Modality to Create Abscopal Effects: Current and Future Practices: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086111/ The Abscopal Effect: A Reemerging Field of Interest: https://ascopost.com/issues/november-25-2018/the-abscopal-effect-a-reemerging-field-of-interest/ BackTable VI Episode #402 - Immunotherapy in HCC: Evolving Treatment Paradigms: https://www.backtable.com/shows/vi/podcasts/402/immunotherapy-in-hcc-evolving-treatment-paradigms Tavo and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Either Pembrolizumab or Nivolumab Treatment (Keynote-695): https://clinicaltrials.gov/study/NCT03132675 PANFIRE-3 Trial: Assessing Safety and Efficacy of Irreversible Electroporation (IRE) + Nivolumab + CpG for Metastatic Pancreatic Cancer: https://classic.clinicaltrials.gov/ct2/show/NCT04612530 Radiofrequency Ablation for the Palliative Treatment of Bone Metastases: Outcomes from the Multicenter OsteoCool Tumor Ablation Post-Market Study (OPuS One Study) in 100 Patients: https://pubmed.ncbi.nlm.nih.gov/33129427/ The improvement of irreversible electroporation therapy using saline-irrigated electrodes: a theoretical study (Northwestern study): https://pubmed.ncbi.nlm.nih.gov/21728392/ Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer: https://www.nature.com/articles/s41467-019-08782-1

future challenges building market medicine therapy birth patients next level northwestern efficacy immunotherapy irreversible modality news articles radiation therapy pembrolizumab aaron fritts

Ep. 71 Next Level Electroporation Therapy: The RadioClash Story with Dr. John Qiao

BackTable Innovation

Play Episode Listen Later Mar 8, 2024 50:19

In this episode of the BackTable Podcast, host Dr. Aaron Fritts interviews guest Dr. John Qiao about exploration of physicians' role in medical innovation, particularly among interventional radiologists. Dr. Qiao shares insightful information about the origin of RadioClash and details his journey as an entrepreneur. Through this discussion, Dr. Qiao covers the challenges encountered during the startup phase, the invention of a single-probe electroporation device, and the future applications of this novel medical technology. The episode concludes with broader advice on how to manage the demands of professional work, entrepreneurship, and personal life. --- SHOW NOTES 00:00 - Introduction 02:39 - Dr. Qiao's Journey into Medicine and Entrepreneurship 11:40 - Birth of Radioclash: A Unique Solution for Cancer Treatment 17:58 - Future of RadioClash: Targeting Metastatic Cancer 25:20 - Future of Electroporation Therapy 35:21 - Challenges of Building a Company 44:37 - Path to Market and Future Plans 47:28 - Balancing Clinical Practice and Entrepreneurship --- RESOURCES RadioClash website: https://www.radioclash.co/ News Article on Dr. John Qiao: https://voyagehouston.com/interview/meet-john-qiao-m-d-of-radioclash-ltd-co/ Radiation Therapy as a Modality to Create Abscopal Effects: Current and Future Practices: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086111/ The Abscopal Effect: A Reemerging Field of Interest: https://ascopost.com/issues/november-25-2018/the-abscopal-effect-a-reemerging-field-of-interest/ BackTable VI Episode #402 - Immunotherapy in HCC: Evolving Treatment Paradigms: https://www.backtable.com/shows/vi/podcasts/402/immunotherapy-in-hcc-evolving-treatment-paradigms Tavo and Pembrolizumab in Patients With Stage III/IV Melanoma Progressing on Either Pembrolizumab or Nivolumab Treatment (Keynote-695): https://clinicaltrials.gov/study/NCT03132675 PANFIRE-3 Trial: Assessing Safety and Efficacy of Irreversible Electroporation (IRE) + Nivolumab + CpG for Metastatic Pancreatic Cancer: https://classic.clinicaltrials.gov/ct2/show/NCT04612530 Radiofrequency Ablation for the Palliative Treatment of Bone Metastases: Outcomes from the Multicenter OsteoCool Tumor Ablation Post-Market Study (OPuS One Study) in 100 Patients: https://pubmed.ncbi.nlm.nih.gov/33129427/ The improvement of irreversible electroporation therapy using saline-irrigated electrodes: a theoretical study (Northwestern study): https://pubmed.ncbi.nlm.nih.gov/21728392/ Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer: https://www.nature.com/articles/s41467-019-08782-1

future challenges building market medicine therapy birth patients next level northwestern efficacy immunotherapy irreversible modality news articles radiation therapy pembrolizumab aaron fritts

S8 Ep97: FDA Approval Insights: Enfortumab Vedotin Plus Pembrolizumab in Locally Advanced/Metastatic Urothelial Carcinoma

fda ev locally fda approval metastatic carcinoma pembrolizumab

Play Episode Listen Later Feb 12, 2024 9:06

Dr Galsky discusses the FDA approval of enfortumab vedotin plus pembrolizumab for patients with locally advanced or metastatic urothelial cancer, key efficacy and safety data from the EV-302 trial, and future directions in urothelial cancer research.

ASCO GU 2024: Adjuvant Pembrolizumab in Bladder Cancer

The Uromigos

Play Episode Listen Later Jan 27, 2024 33:17

Andrea Apolo describes the results of this positive trial.

bladder cancer adjuvant pembrolizumab asco gu

Berdazimer for Molluscum Contagiosum; Pembrolizumab for Cervical Cancer; GLP-1 RAs and Suicidal Thoughts; Cognitive Impairment Test; SH-105 for Breast and Ovarian Cancer; DBS System for Parkinson's; NexoBrid for Pediatric Burns; Laser Platform for LASIK

prostate cancer crpc pembrolizumab

Play Episode Listen Later Jan 15, 2024 12:04

Visit nascentmc.com to get medical writing assistance for your company. Visit learnAMAstyle.com for free downloads about medical editing and writing in the AI era. See full write up and supporting links for this episode at nascentmc.com/podcast. Summary: § FDA has approved berdazimer topical gel, 10.3% (Zelsuvmi), as the first novel drug for molluscum contagiosum, a viral skin infection affecting adults and children over 1 year old. § Pembrolizumab (Keytruda) is now approved for stage III-IVA cervical cancer treatment in combination with chemoradiotherapy, based on positive data from the KEYNOTE-A18 trial. It's the third indication for cervical cancer and 39th overall § The FDA issued a drug safety communication regarding GLP-1 receptor agonists and suicidal thoughts, finding no clear relationship between them. § BrainSee, a noninvasive test, approved for predicting progression from amnestic mild cognitive impairment (aMCI) to Alzheimer's dementia using MRI and cognitive assessments, offering a same-day alternative to traditional methods. § SH-105, a novel treatment for breast and ovarian cancers, had its NDA accepted with a target action date set for June 29, 2024, offering a differentiated injectable product. § Medtronic's Percept RC deep brain stimulation system received FDA approval for Parkinson's. § NexoBrid, a topically administered biological product for burn treatment, expanded its label to include pediatric patients based on positive results from clinical trials. § The FDA approved the Teneo excimer laser platform for LASIK surgery, featuring high-speed eye tracking and fast ablation times for precise vision correction in individuals aged 22 and older. See full write up and supporting links at nascentmc.com/podcast.

Episode 281: The Uromigos Paper of the Month - Lu-177 with Pembrolizumab in Prostate Cancer

The Uromigos

Play Episode Listen Later Dec 8, 2023 25:23

Rahul Aggarwal describes his phase 1/2 study with only 1 cycle of Lu-177 in CRPC.

Nirogacestat For Desmoid Tumors, Pirtobrutinib for CLL/SLL, Enfortumab Vedotin With Pembrolizumab for UC, Lisocabtagene Maraleucel for CLL/SLL, Xanomeline-trospium for Schizophrenia, Roflumilast for AD

keynote asco fda approval perioperative esmo pembrolizumab

Play Episode Listen Later Dec 4, 2023 9:01

Summary: Check out our free downloads at nascentmc.com: Implementing AMA Style – 8 Things to Get Right in Your Next Project Needs Assessments – 7 Essentials for Getting Funded Working With Your Medical Writer – 8 Ways to Get the Most out of Them See the full write ups for today's episode at nascentmc.com/podcast Here are the highlights: Nirogacestat (Ogsiveo) For Desmoid Tumors: Nirogacestat is the first FDA-approved drug for treating progressing desmoid tumors in adults, offering a significant improvement in response rate compared to placebo in a major trial. Pirtobrutinib (Jaypirca) in CLL/SLL: The FDA granted accelerated approval for pirtobrutinib to treat adult patients with CLL/SLL who have undergone at least two prior therapies, with its effectiveness based on response rates from the BRUIN trial. Enfortumab Vedotin (Padcev) With Pembrolizumab (Keytruda) for Urothelial Cancer: The FDA is reviewing a combination treatment of enfortumab vedotin and pembrolizumab for urothelial cancer under priority review, showing significant improvement in survival rates compared to chemotherapy in a Phase 3 study. Lisocabtagene Maraleucel (Breyanzi) for CLL/SLL: The FDA is reviewing lisocabtagene maraleucel for expanded use in treating CLL/SLL patients who have relapsed after BTKi and BCL2i treatments, based on positive results from the TRANSCEND CLL 004 study. Xanomeline-trospium (KarXT) for Schizophrenia: The FDA is considering xanomeline-trospium for treating schizophrenia, with potential benefits over traditional treatments in reducing common antipsychotic side effects, based on the EMERGENT program results. Roflumilast Cream for Atopic Dermatitis: The FDA is reviewing roflumilast cream for treating atopic dermatitis in adults and children, supported by positive results from the INTEGUMENT-1 and INTEGUMENT-2 studies, with a potential for simplification in disease control. See the full write ups for today's episode at nascentmc.com/podcast Intro and outro music Garden Of Love by Pk jazz Collective

phase collective fda essentials pk tumors schizophrenia get right emergent bruin pembrolizumab btki

FDA Approval: Perioperative Pembrolizumab and KEYNOTE 671

Lung Cancer Considered

Play Episode Listen Later Nov 28, 2023 45:31

Host Dr. Narjust Florez leads a discussion about the data from the KEYNOTE 671 trial, presented at ASCO 2023 and ESMO 2023, that led to the first approval of the combination of pembrolizumab plus chemotherapy in the neoadjuvant and adjuvant setting.

Capivasertib for Breast Cancer, Repotrectinib for NSCLC, Enzalutamide for Prostate Cancer, Pembrolizumab for Stomach Cancer, Hypertension Device

collective fda essentials breast cancer device pk prostate cancer hypertension get right rdn akt her2 nsclc stomach cancer pembrolizumab ros1

Play Episode Listen Later Nov 20, 2023 10:00

ESMO 2023 Lung Cancer - Chapter 2 Highlights – PAPILLON, MARIPOSA, MARIPOSA-2, LIBRETTO-431

treatments chemo lung cancer mariposa papillon egfr libretto esmo pembrolizumab advanced nsclc community oncology

Play Episode Listen Later Nov 13, 2023 18:28

In discussion with Dr. Alexander Spira, covering the ESMO 2023 Lung Cancer Highlights from Community Oncology perspective. We covered 4 important practice informing studies with Dr. Spira: - PAPILLON – Amivantamab Plus Chemo in Advanced NSCLC with EGFR Exon 20 Insertions - MARIPOSA – Amivantamab Plus Lazertinib Versus Osimertinib as First-line Treatment in EGFR-mutated Advanced NSCLC - MARIPOSA-2 – Amivantamab Plus Chemo (with or without Lazertinib) vs Chemo in EGFR-mutated Advanced NSCLC After Progression on Osimertinib - LIBRETTO-431 – First-line Selpercatinib or Chemo and Pembrolizumab in RET Fusion-Positive Advanced NSCLC

Pembrolizumab, Secukinumab, Ustekinumab biosimilar, Vonoprazan, Abatacept, Exa-cel

Play Episode Listen Later Nov 6, 2023 8:26

Summary: Check out our free downloads at nascentmc.com: Implementing AMA Style – 8 Things to Get Right in Your Next Project Needs Assessments – 7 Essentials for Getting Funded Working With Your Medical Writer – 8 Ways to Get the Most out of Them See the full write ups for today's episode at nascentmc.com/podcast Here are the highlights: Pembrolizumab (Keytruda) has received FDA approval for the treatment of metastatic biliary tract cancer, both in combination with chemotherapy and as a monotherapy. The approval is based on the positive outcomes of the KEYNOTE-966 trial, where patients receiving pembrolizumab plus chemotherapy demonstrated a statistically significant improvement in overall survival compared to those receiving a placebo with chemotherapy. Common adverse reactions included hematologic abnormalities, pyrexia, fatigue, cholangitis, and hepatic enzyme elevations. Approval was granted to Merck. Secukinumab (Cosentyx) has gained FDA approval for the treatment of moderate-to-severe hidradenitis suppurativa (HS), making it the first FDA-approved IL-17A inhibitor for this condition. Approval is based on results from the SUNSHINE and SUNRISE trials, showing significant improvements in response rates in HS patients treated with secukinumab compared to placebo. Ustekinumab-auub (Wezlana) has been granted FDA approval as an interchangeable biosimilar for Stelara, offering treatment options for multiple inflammatory diseases. It is indicated for moderate to severe plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis in adult patients, as well as pediatric patients with plaque psoriasis and psoriatic arthritis. Vonoprazan (Voquezna) has received FDA approval for the treatment of erosive esophagitis (GERD). As a potent potassium-competitive acid blocker (PCAB), it offers an alternative to proton pump inhibitors (PPIs). Approval is based on the PHALCON-EE study, where vonoprazan demonstrated noninferiority to lansoprazole in healing GERD. Abatacept (Orencia) has been expanded for use in pediatric patients aged 2 years and older to treat psoriatic arthritis. Originally approved for rheumatoid arthritis in adults in 2005, abatacept was also approved for adult psoriatic arthritis in 2017. Exa-cel, a CRISPR-based therapy developed by CRISPR Therapeutics and Vertex, is under FDA review for sickle cell disease. The advisory panel has found it safe for clinical use, with potential approval expected in December. Exa-cel aims to alleviate sickle cell symptoms through gene editing technology Intro and outro music Garden Of Love by Pk jazz Collective

collective fda essentials keynote sunrise approval hs crohn pk crispr merck gerd get right vertex ppis exa biosimilar pembrolizumab crispr therapeutics stelara il 17a pcab

Bimzelx (bimekizumab); Keytruda (pembrolizumab); Opdivo (nivolumab); Zilbrysq (zilucoplan); and more

west approval embark nsclc pembrolizumab nivolumab monotherapy

Play Episode Listen Later Oct 24, 2023 15:12

Check out our free downloads at nascentmc.com: Implementing AMA Style – 8 Things to Get Right in Your Next Project Needs Assessments – 7 Essentials for Getting Funded Working With Your Medical Writer – 8 Ways to Get the Most out of Them See the full write ups for today's episode at nascentmc.com/podcast Here are the highlights: BIMZELX (bimekizumab) for Moderate-to-Severe Plaque Psoriasis: The FDA approved BIMZELX for treating moderate-to-severe plaque psoriasis, making it the first psoriasis treatment targeting interleukin 17A and interleukin 17F. The approval follows data from Phase 3 trials and comes after a prior delay due to COVID-related travel restrictions. Neoadjuvant Pembrolizumab for NSCLC: The FDA approved pembrolizumab for neoadjuvant and post-surgical adjuvant treatment in patients with resectable non-small cell lung cancer, adding to its indications in multiple tumor types. The approval was based on the phase 3 KEYNOTE-671 trial data. Adjuvant Nivolumab for Stage IIB/C Melanoma: The FDA granted approval to nivolumab for adjuvant treatment of melanoma in patients aged 12 and older with resected stage IIB or IIC disease, addressing the need to reduce the risk of recurrence. This is supported by the CheckMate76K trial data. Zilucoplan for Myasthenia Gravis: UCB Pharma's zilucoplan, a complement C5 inhibitor, received FDA approval for treating myasthenia gravis (MG), demonstrating rapid improvements in MG-specific efficacy outcomes based on the phase 3 RAISE study. IDP-126 (Cabtreo) First Triple-Combination Drug for Acne: Cabtreo, a triple combination topical gel for acne, received FDA approval as the first fixed-dosed, triple-combination treatment for patients aged 12 and older with acne vulgaris. Penbraya Meningococcal Vaccine in Adolescents: The FDA approved Penbraya, a vaccine covering the five most common serogroups causing meningococcal disease in adolescents, based on Phase 2 and Phase 3 trial data. It's administered as a two-dose series. Voxzogo in Dwarfism: Vosoritide (Voxzogo) was expanded for use in children under 5 with achondroplasia, the most common form of short-limbed dwarfism, after demonstrating safety and efficacy in this age group. QLOSI for blurry age-related near vision: The FDA approved QLOSI, a preservative-free eye solution, for the treatment of presbyopia, improving near visual acuity by pupil modulation and increasing depth of field. Maxigesic IV for Post-Op Pain: Maxigesic IV, a combination of paracetamol and ibuprofen, gained FDA approval for post-operative pain management, offering faster pain relief and reduced opioid usage. Xphozah for Chronic Kidney Disease: Tenapanor (Xphozah) was approved as an add-on therapy for patients with chronic kidney disease who can't tolerate or respond adequately to phosphate binders, based on phase 3 trial data, addressing high blood phosphorus levels. Zymfentra infliximab biosimilar for ulcerative colitis and Crohn's disease: Zymfentra, a subcutaneous infliximab biosimilar, received FDA approval for maintenance therapy in adults with moderately to severely active ulcerative colitis and Crohn's disease, based on LIBERTY-UC and LIBERTY-CD study findings. Intro and outro music Garden Of Love by Pk jazz Collective

covid-19 raise phase collective fda essentials keynote crohn pk mg moderate get right c5 idp keytruda 17a iic iib pembrolizumab nivolumab opdivo

Enzalutamide monotherapy? Plus, nivolumab & pembrolizumab approval updates

OncoPharm

Play Episode Listen Later Oct 19, 2023 17:05

This week we discuss the continued push to introduce 2nd generation androgen inhibitors earlier into treatment with the EMBARK trial. Nivolumab and pembrolizumab, pemrolizumab and nivolumab. Again and again. Their role (and approvals) for adjuvant melanoma make sense. But what to think about their use for NSCLC in the neoadjuvant setting? West commentary: https://dailynews.ascopubs.org/do/should-induction-chemoimmunotherapy-lead-us-broaden-our-definition-resectability-nsclc

2023 World Conference on Lung Cancer Highlights | Dr. Stephen Liu | Oncology Brothers #2023

brothers os oncology cns lung cancer chrysalis orr evoke pfs egfr world conference pembrolizumab highlights dr osimertinib community oncology

Play Episode Listen Later Sep 21, 2023 24:38

In discussion with Dr. Stephen Liu, covering the World Conference on Lung Cancer Highlights from Community Oncology perspective. We covered 4 important practice informing studies with Dr. Liu: - FLAURA2 - studying the importance of Osimertinib + chemo vs. Osimertinib in EGFRm patients, PFS benefit in the combination arm, though pending OS and most benefit derived in patients with CNS mets - CHRYSALIS-2 - post progression on EGFR therapy, there is ORR benefit from adding Amivantamab in combination with Lazertinib plus chemo - MARS2 - when compared surgery followed by chemo vs chemo alone, chemo alone had better outcomes in patients with resectable mesothelioma - EVOKE-02 - Sacituzumab approved bladder and breast cancer, was tested here along with Pembrolizumab in 1st line mNSCLC setting, with more data to come to confirm its arrival in this space #WCLC #IASLC #LungCancer #2023 #cancer #oncology #oncbrothers Website: http://www.oncbrothers.com/ Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

EV-103 Study by Dr. Jonathan Rosenberg led to the FDA Approval of Enfortumab + Pembrolizumab