Podcasts about vegf

Next-generation anti-VEGF agents are designed for durability. But does that actually change the rate at which they're administered? David Miller, MD, joins us to review a pair of ARVO 2025 presentations that examined his clinic's real-world administration patterns for bevacizumab (Avastin, Genentech), faricimab (Vabysmo, Genentech/Roche), and high-dose aflibercept (Eylea HD, Regeneron). What were the differences—and did they really matter?  Also, Robert Wang, MD, helped us understand the state of play in the TKI pipeline as he shared data from the phase 2b ODYSSEY study. What are the latest data on CLX-AX (Clearside Biomedcial)? And where does it stack up against the other TKIs in the pipeline? Stick with us to find out. 

Dr. Rajesh Rao sits down with Dr. Sophie J. Bakri and medical student Marie-Michele Macaron to discuss their systematic Review and meta-analysis on the efficacy and safety of anti-VEGF and panretinal photocoagulation for the treatment of proliferative diabetic retinopathy. From their Ophthalmology Retina article, “Anti-VEGF Injections vs. Panretinal Photocoagulation Laser Therapy for Proliferative Diabetic Retinopathy: A Systematic Review and Meta-Analysis.” Anti-VEGF Injections vs. Panretinal Photocoagulation Laser Therapy for Proliferative Diabetic Retinopathy. Macaron, Marie-Michele et al. Ophthalmology Retina, Volume 9, Issue 2, 105 - 121.

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.

Story at-a-glance Women with chronic migraines and body-wide pain were far more likely to have poor oral health, with over half falling into the lowest oral health categories in a new study Specific oral bacteria, including Mycoplasma salivarium and Gardnerella vaginalis, were significantly more common in women who reported frequent migraines and widespread pain Harmful oral microbes don't stay in your mouth; once gum tissue is inflamed, these bacteria enter your bloodstream, disrupt the immune system, and trigger systemic pain A less diverse oral microbiome was found in women with migraines and gut pain, making it easier for pain-triggering bacteria to dominate and inflame nerve pathways Inflammatory chemicals produced by oral bacteria — like calcitonin gene-related peptide (CGRP) and vascular endothelial growth factor (VEGF) — are directly involved in migraine and fibromyalgia, showing how poor oral hygiene can set off whole-body pain responses

In his effort to onshore manufacturing, President Donald Trump issued an executive order on Monday afternoon ordering the FDA to ease permitting processes for new and expanded U.S. facilities. The announcement comes as more and more Big Pharma companies commit billions to expanding their U.S. footprints. Bristol Myers Squibb CEO Christopher Boerner announced this week that the company will pump $40 billion into its stateside operations over the next five years, even as the pharma executes a massive cost-cutting effort that involves shaving $3.5 billion from expenses by 2027 and cutting thousands of jobs, including another 516 in New Jersey, according to a May WARN notice.  In other policy news, the Department of Health and Human Services on Wednesday said it will require all new vaccines to be tested in placebo-controlled trials to earn FDA approval but some vaccine experts have raised concerns about this approach. Meanwhile, turmoil still envelopes the FDA, with staff cuts and rehires continuing at a dizzying pace. On Monday, several states sued HHS, saying that the cuts offload critical functions and costs onto the states and impede public health efforts.  As Q1 earnings season for Big Pharma begins to wind down, there are still headlines coming from the biotech sector. Vertex revealed last week that it is abandoning all of its adeno-associated virus vector work, while BioNTech on Monday announced that tariffs could get in the way of its ambitious plans for a closely watched PD-L1-VEGF therapy. Moderna, meanwhile, continues its fall from COVID grace, missing Q1 revenue expectations and announcing plans to reduce operating expenses by around $1.5 billion by 2027.   In the weight loss space, Novo Nordisk announced on Friday that the FDA has accepted the application for a pill version of Wegovy, with a decision expected this fall. Novo has also struck partnerships with CVS and Hims & Hers pharmacies to market injectable Wegovy, drawing the attention of Eli Lilly CEO David Ricks.   Also this week, check out BioSpace's deep dives into advances in base editing—a technology that's been touted as a “safer” CRISPR—and Summit Therapeutics' push to bring closely watched PD-1/VEGF immunotherapy ivonescimab to the U.S. market after its recent approval in China. 

In this JCO PO Article Insights episode, host Harold Tan summarizes Low Kynurenine Levels Among Exceptional Responders on Phase Ib Trial of the HDAC Inhibitor Abexinostat with Pazopanib by Tsang et al, published November 07, 2024. Transcript Harold Nathan Tan: Welcome to JCO Precision Oncology Article Insights, where we explore cutting-edge discoveries in the world of cancer treatment and research. I'm Harold Nathan Tan, your host, and today we're taking a focused look at a compelling phase Ib trial led by Dr. Tsang, which investigates a combination of abexinostat, a histone deacetylase inhibitor, with pazopanib, a VEGF-targeting tyrosine kinase inhibitor, in patients with advanced solid tumors. VEGF inhibition has long been an established therapeutic strategy across a wide range of tumor types, including colorectal, ovarian, sarcoma, and renal cell carcinoma. These agents function by disrupting tumor angiogenesis, effectively limiting oxygen and nutrient delivery to malignant cells and contributing to improved survival outcomes. However, over time, acquired resistance remains a significant challenge. A key mechanism implicated in this resistance involves the upregulation of hypoxia-inducible factor 1-alpha, or HIF-1-alpha for short, a master regulator of angiogenesis that restores VEGF signaling under hypoxic conditions. Interestingly, HIF-1-alpha overexpression is mediated by histone deacetylases, especially HDAC2. Preclinical studies suggest that HDAC2 inhibition can suppress tumor cell migration and downregulate HIF-1-alpha activity, effectively disabling a critical escape pathway used by tumors under VEGF pressure. Moreover, combining HDAC inhibition with VEGF blockade has demonstrated synergy in pazopanib-resistant tumor models, forming a compelling rationale for this dual approach. The phase Ib trial by Tsang et al. was designed to evaluate the safety, tolerability, and preliminary efficacy of this dual-targeted approach in patients with heavily pretreated advanced solid tumors. A dose-expansion cohort focused on individuals with renal cell carcinoma, allowing for more detailed evaluation in this population. A central component of this study was the incorporation of biomarker analysis, particularly regarding HDAC2 expression levels. The results were noteworthy. Patients with high HDAC2 expression achieved a progression-free survival of 7.7 months compared to only 3.5 months in those with low expression. Even more compelling, overall survival reached 32.3 months for those with a high HDAC2 expression versus just 9.2 months for those with low expression. This suggests the potential role for HDAC2 as a predictive biomarker for response to combination HDAC and VEGF-targeted therapy. The authors also explored the metabolic landscape of these patients, conducting metabolomic analysis focused on kynurenine, a key tryptophan catabolite known to contribute to the immune suppression in the tumor microenvironment. Its reduction is driven by HIF-1-alpha and inflammatory cytokines, including interleukin-6 and tumor necrosis factor-alpha. What they found was striking. Exceptional responders, defined as patients with treatment responses lasting more than 3 years, had consistently lower levels of kynurenine both before and after treatment. This finding introduces kynurenine as a potential metabolic biomarker. It suggests that patients with lower kynurenine levels may have a less immunosuppressive microenvironment, making them more responsive to the combined effects of HDAC inhibition and VEGF blockade. Of note, VEGF levels themselves did not significantly differ between responders and nonresponders, highlighting that the treatment benefit is not purely VEGF-mediated but likely driven by epigenetic and metabolic modulation. On the safety front, the combination of abexinostat and pazopanib was generally well tolerated. However, this study did report a correlation between higher plasma concentrations of abexinostat and an increased incidence of thrombocytopenia, a class effect associated with HDAC inhibitors. This trial introduces several key considerations for future research. First, it calls for validation of HDAC2 as a predictive biomarker. If confirmed in larger cohorts, HDAC2 expression could be used to select patients most likely to benefit from HDAC inhibitor-based regimens, transforming how we approach trial enrollment and treatment planning. Second, the link between low kynurenine and exceptional response supports further investigation into how metabolic pathways can influence treatment response to combined HDAC and VEGF inhibition. Overall, HDAC inhibitors hold significant promise in precision oncology. Realizing their full therapeutic potential requires a deeper understanding of HDAC biology, refined combination strategies, and thorough preclinical and clinical evaluations tailored to individual patient profiles. This study exemplifies the potential of epigenetic-metabolic crosstalk as a therapeutic vulnerability and underscores the importance of precision stratification in clinical trial design. As research in this space progresses, the integration of molecular, epigenetic, and metabolic profiling will be essential in optimizing the use of HDAC inhibitors and expanding their role within precision oncology. Thank you for tuning into JCO Precision Oncology Article Insights. Don't forget to subscribe and join us next time as we explore more groundbreaking research shaping the future of oncology. Until then, stay informed and stay inspired.   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.

Dr. Sarah Mrejen (France), Associate Professor Salomon Cohen (France), and Associate Professor Dinah Zur (Israel) explore how neovascular AMD phenotype may influence imaging choices, patient dialogue, and treatment plans. From proactive vs. conservative strategies to new anti-VEGF agents and PCV diagnosis, this expert-led discussion offers key insights into personalising care in retinal disease.

Send us your feedbackEye injections can feel daunting, but they don't have to be. In this episode of the My Macular and Me podcast, orthoptist and advanced practitioner Catherine Williamson answers common questions and clears up misconceptions to help you feel more prepared, informed and reassured about treatment. For more information on injections and other treatments, visit our website.The Macular Society has been supporting people with macular conditions for over 30 years. The right information and support can help people overcome their worries and retain their independence. We provide free information and support to those with macular disease, along with their family and friends. If you or a family member need advice or support, please make sure to reach out. No one has to face macular disease alone. Please call us on 0300 3030 111.

Dr. Wu discusses prospective cognitive outcomes of children who had treatment for Retinopathy of Prematurity. The analysis suggests that cognitive outcomes were similar for children who had either laser or anti-VEGF injections for ROP treatment.  Dr. Wu will be one of the invited guest speakers at the Canadian Retina Society meeting in Vancouver, BC from April 25-April 27, 2025. You can register for this meeting at: https://crsscr.ca/meeting   Discussed article: Wu PL, Shih CP, Huang YS, Chen HC, Hsueh YJ, Lee CW, Chiang MC, Lien R, Lee CC, Chu SM, Chou HD, Liu L, Chen KJ, Hwang YS, Lai CC, Wu WC. ADMINISTERING INTRAVITREAL BEVACIZUMAB FOR RETINOPATHY OF PREMATURITY: 8-Year Cognitive Outcomes In A Prospective Cohort. Retina. 2024 Nov 1;44(11):1952-1960. doi: 10.1097/IAE.0000000000004222. PMID: 39121508.

Loss of leadership, cuts to staffing and a proposed reorganization at FDA have heightened biotech risk amid an already turbulent macroeconomic climate, according to BioCentury's Washington editor Steve Usdin. On the latest BioCentury This Week podcast, BioCentury's editors discuss how the turmoil at FDA could affect a sector already grappling with the uncertainty brought by the Trump administration's trade war.The editors also explore the growing pipeline of VEGF-targeted bispecifics in a preview of upcoming presentations at annual meeting for the American Association for Cancer Research (AACR). And they discuss how companies may once again need to lean on their bear market survival toolkit, as part of BioCentury's 2Q25 Financial Markets Preview. This episode of BioCentury This Week was sponsored by RemeGen Co.View full story: https://www.biocentury.com/article/65556600:01 - Sponsor Message: RemeGen Co. 01:19 - FDA and Tariffs Turmoil16:54 - AACR Preview20:44 - Bear Market ToolkitTo submit a question to BioCentury's editors, email the BioCentury This Week team at podcasts@biocentury.com.Reach us by sending a text

Muito se fala sobre a creatina causar queda de cabelo. Mas... e se for exatamente o oposto?Neste episódio, o Dr. Ademir Carvalho Leite Júnior analisa os estudos mais relevantes sobre a creatina — um dos suplementos mais utilizados do mundo — e mostra como ela pode contribuir para a bioenergia dos folículos, fortalecer os fios e até estimular o crescimento capilar.Ouça agora e descubra:• Por que a creatina pode beneficiar o couro cabeludo• Como ela melhora a força e elasticidade do fio• A relação entre ATP, VEGF e o ciclo capilar• E quais produtos cosméticos já utilizam esse ativo

Dr. John Heymach from MD Andersons joins us to discuss a novel PD1/VEGF bispecific agent in lung cancer and if there are applicaitons in GU malignancies.

What causes central serous chorioretinopathy (CSC), and how should it be managed? In this episode, experts Camiel Boon, Sobha Sivaprasad, and Gemmy Cheung discuss the latest insights into CSC and the pachychoroid spectrum, including new imaging findings, risk factors, and treatment options like PDT, laser, and anti-VEGF

Dr. Shannon Westin and her guest, Dr. Breelyn Wilky, discuss the JCO article, "“Botensilimab (Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti-PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas." TRANSCRIPT  Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast where we get in depth on research that has been published in the Journal of Clinical Oncology. I am your host, Gynecologic Oncologist and Social Media Consultant Editor of the JCO, Shannon Westin. I serve here from the University of Texas MD Anderson Cancer Center. And I am so excited to welcome Dr. Breelyn Wilky. She's an Associate Professor and the Director of Sarcoma Medical Oncology in the Department of Medicine Division of Medical Oncology, and the Cheryl Bennett & McNeilly family endowed chair in Sarcoma Research, the Deputy Associate Director of Clinical research at the University of Colorado Cancer Center. Welcome. Dr. Breelyn Wilky: Thank you so much. I'm delighted to be here. Shannon Westin: And with all those titles, I'm super impressed that she was able to complete the manuscript that we're going to discuss today, which is “Botensilimab (Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti-PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas.” And this was published in the JCO on January 27, 2025. And please note, our participants do not have any conflicts of interest. So this is exciting. Let's first level set. Can you review with us just the current state of sarcoma incidents, survival outcomes, that kind of thing so we all know where we're starting? Dr. Breelyn Wilky: Yes. So, you know, sarcomas are really, I like to call them the black box cancer type. And the big thing is that there's really more than a hundred different kinds of sarcomas, which collectively altogether make up only 1% of adult cancers. And so we talk about these as being bone and soft tissue tumors, but really, the heterogeneity is just incredible. You're talking maybe 10,000 to 12,000 new cases of soft tissue sarcoma per year, which is pretty rare in the grand scheme of things. And the trouble with these is that while you can cure sarcomas if you find them early and they're localized, when they metastasize and spread and are not resectable, we're looking at median overall survivals of really only 12 to 18 months, even, you know, with our best therapies that we have. So, really there's just a dire need for new treatments for this really tough group of diseases. Shannon Westin: Yeah, I agree. I'm a gynecologic oncologist, and we have our little subset of sarcomas that I know there's a little bit out of every one. So I'm really excited to pull this manuscript as one of our podcasts offerings because I think we're all seeing these patients in the clinic and certainly our listeners that have sarcoma or have family members with sarcoma, this is so good to have a real focus on a rare group of tumors that have been a little bit lumped together. Now, with that being said, I know this is such a heterogeneous population, but can you briefly overview a little bit around the standard of care for treatment of recurrent sarcomas? Dr. Breelyn Wilky: We have actually been using the same drugs really since about the 1970s, and up until very recently, nothing had really challenged doxorubicin, the old ‘red devil', like we used to call it. And this has been the mainstay of treatment for metastatic sarcomas and really used across the board. In the GYN literature, for uterine leiomyosarcoma, we did see some promising activity with the combination of doxorubicin and trabectedin coming out of the French group. But, except for that study, no combination therapy or new drug has been proven better in terms of overall survival compared to doxorubicin monotherapy, really over 40, 50 years. So it's definitely a tough situation. Now, we do have other drugs that we use, so most patients will wind up getting doxorubicin-based therapy. There's a couple of other regimens that we'll reach to, like gemcitabine docetaxel. And once you get into the specific subtypes, we have some approvals in liposarcomas and leiomyosarcomas for some other drugs. But really the median progression for survival for most of these regimens is somewhere four to six months. And response rates typically are somewhere like 10%, 15% for most of these. So it's really just a very tough field and a tough group of patients to try to make an impact for. Shannon Westin: So let's talk a little bit more kind of getting focused on what you've studied here. What's been the role of immunotherapy thus far in the treatment of sarcomas maybe prior to this particular study? Dr. Breelyn Wilky: Clearly, we all know that immune therapy has just changed cancer care forever over the last few years for so many different types of cancers and diseases like melanoma and renal cell and lung cancer have just been transformed by checkpoint inhibitors specifically directed against PD-1 or CTLA-4 or both. And so, of course, you know, sarcoma docs we're super excited to try to see if these might potentially have activity in our tumors as well. I never had seen myself in my career getting into immunotherapy until I was able to run an investigator-initiated study during my role in Miami, where we combined pembrolizumab, so PD-1 inhibitor, with axitinib which was a pan-VEGF inhibitor. And lo and behold, like I had patients that I was seeing responses when other treatments, all those chemotherapies I was just talking about had failed. And one of my first patients I treated was about a 60-year-old lady with something called cutaneous angiosarcoma. So this is a blood vessel sarcoma all over her face. And we had treated her with 10 different therapies, all the chemotherapy regimens, targeted therapies, clinical trials, and nothing was working. But I put her on a phase 1 trial with a baby dose of CTLA-4 and this woman had a complete response. And so for me, once I saw it work in even just those couple of patients, like that was nothing that we'd ever seen with our chemotherapy regimens. And so that sort of shifted my career towards really focusing on this, and this is about the time where some of the studies started to come out for sarcomas. And the take home with sarcoma is about 20% of sarcomas have this sort of immune hot physiology. So what that basically means is if you look at gene expression of immune related gene signatures, or you look for infiltrating T-cells, sort of the SWAT team of our immune system, like you can find those in the tumors. And it's sort of evidence that the immune system had some clue for that 20% of patients that this was a foreign tumor and that it should be attacking it and maybe just needed a little help. But globally, about 80% of sarcomas are these immune cold tumors, which means the immune system has no clue that these things are even a threat. And there's almost no immune activation, very, very few antigens. In other cancer types, high neoantigens or tumor antigens help the immune system work better. And so that basically goes with what we've seen with trials of PD-1 or CTLA-4 blockade. About 20% of sarcomas, with some exceptions, can respond. But really 80% across the board, you're stuck, you just can't get them to be recognized. And so that's where I think this data is so interesting is there's some signals of activity in these immune cold tumors which, at least historically with the trials we've done so far, we really haven't seen that with sort of the traditional checkpoints. Shannon Westin: So I think now this is a great time to maybe talk about the study design in general, the eligibility and just give us kind of a run through of that. Dr. Breelyn Wilky: So this trial was a phase 1 trial of a drug called botensilimab, which is a next generation CTLA-4 directed immune modulator. So what makes botensilimab different is that the CTLA-4 end is very similar to other CTLA-4 inhibitors that are out there, but it's been engineered on the back end of the molecule that binds to Fc gamma receptors to basically bind tighter with higher affinity. And what this translates to in laboratory models and increasingly now in patients is it does a better job of priming, of educating our T cells, our, again, these highly intelligent antigen specific cells, but also natural killer cells. It does a better job of sort of educating those. It helps to activate macrophages and other supporting actors in the immune response. And so the idea here is that there's evidence that botensilimab may do a better job at creating new responses in immune cold tumors. The study combined either botensilimab as monotherapy or in combination with a PD-1 inhibitor called balstilimab. And this was all comers, really a variety of tumor types. And to date I think we're close to about 500 patients with a variety of solid tumors that have been accrued to this study, this C-800-01 phase 1 trial. This paper reports on the sarcoma patients that were enrolled as part of this study. And so, again, given what I've told you about sarcomas being really immune cold, we were just so excited to have the opportunity to enroll on a next generation immune therapy for these tumors that really we were running into roadblocks trying to use immunotherapy previously. Shannon Westin: It's a very compelling idea and I'm so excited for you to tell people what you found. I think first things first, it was an early phase trial. So why don't we talk a little bit about the safety of the regimen. Was there anything that you didn't expect? Dr. Breelyn Wilky: Right. So similar to other checkpoint inhibitors, you know, the idea is that these drugs can cause immune mediated toxicities, right? So essentially you're revving up the immune system and it can sometimes get a bit confused and start attacking our normal cells, our normal organs, leading to essentially any number of toxicities of basically head to toe, something can get inflamed and you can develop a toxicity from that. So the key take homes with this particular drug with, botensilimab with balstilimab, we saw colitis was sort of the primary immune mediated toxicity and it was about a third of patients, give or take. It happens and it can be aggressive and needs to be managed aggressively. And you know, one of the things that we learned very quickly taking part in this study is how important it is that as soon as patients start to get diarrhea, immunosuppression gets on board. So steroids, early use of TNF alpha blockade, so infliximab for example, if we jumped on it quickly and we recognized it and we got the patients treated, it would resolve fairly quickly and even some patients could remain on treatment. So I think that was sort of the first take home is “Okay if you get colitis, you treat it fast, you treat it early and you can still have patients not only recover, which essentially everybody recovered from this colitis and then being able to continue on treatment and still have their anti-tumor responses.” So that's the first point. The second thing that was really interesting is part of the engineering of botensilimab on the back end of the molecule, it's been designed to decrease complement binding and it's thought that that triggers some of these other toxicities that we've seen with prior CTLA-4 inhibitors like pneumonitis or hypophysitis. We actually don't see that with botensilimab. So there's sort of this selective toxicity that may reflect the design of the molecule. But overall the treatment was, we didn't see any new safety signals that were outside of what we would expect in class. And colitis was sort of the dominant thing that we had to be ready for and ready to manage. Shannon Westin: We've been doing it for a while now, so we kind of know what to do and we can act quickly and really try to mitigate and avoid some of the major toxicities. So that's great that that was what was reflected in what you found. And then of course I think: What about the efficacy?” Right. This is what we care about as practitioners, as patients. Does it work and are there any subtypes that seem to benefit the most from this combination? Dr. Breelyn Wilky: Right. So for the sarcoma patients, we treated 64 patients and 52 of those patients were evaluable for efficacy. So a decent size group of patients in sarcomas, where, you know, typically our trials are pretty small, they're very rare, but we had 52 evaluable with at least one post baseline scan. So that was our criteria. And basically we saw across all of the patients, and keep in mind, these are heavily pre-treated patients, as you mentioned, so a median of 3 prior lines of therapy, so most of these patients had had chemotherapies and then about 20% had also had prior immunotherapy as well. So PD-1 treatments or so on. The overall response rate by RECIST was 19.2% for all of the evaluable patients. And then with iRECIST, which is sort of that immune adapted response criteria that allows for early pseudo progression, we actually had another patient who did have that. And so that response rate was 21.2%. Overall, we were really excited to see this in a heavily pre-treated group of patients. But what was really exciting to me was when we looked at the subset of patients that had angiosarcoma, that blood vessel tumor I was talking about earlier with my other patient. So angios come in two flavors. One is this sort of cutaneous type, or meaning involving the skin that has a UV signature, a UV damage signature, very similar to melanoma. So these tumors tend to have a high mutation burden. And oftentimes there is a track record that we've seen responses with immunotherapy in cutaneous angiosarcomas. But the other group that we deal with is called visceral angiosarcomas. And so these are totally different biologically. These are often driven by mutations in MYC or KDR amplification, and they arise in organs, so primary breast angiosarcoma, not associated with radiation, or they can arise in the liver or the spleen or an extremity. So these are very, very different tumors, and the visceral ones almost never historically have responded to checkpoint inhibitors. So we had 18 patients with angio split - 9 with cutaneous, 9 with visceral. And we were just blown away because the response rate for that group was 27.8%. And if you looked at the responses between the hot ones and the cold ones, it was almost equal and a little bit better in the visceral. So we had a 33% response rate in visceral angiosarcoma, which is crazy, historically speaking, and about 20% again in the cutaneous angios. So for a disease where visceral angio gets treated with chemotherapy, might respond initially, but then rapidly progresses - like these people go through multiple lines of therapy - to have a third of patients responding, and then some of those responses were durable. Our median duration of response for the study was 21.7 months, which is just nuts for sarcomas where we just don't see those sorts of long term benefits with the drugs that we have. So I think those are kind of the two main things. There were other subtypes that had clinical benefit and responses as well in d-diff liposarcoma, soft tissue leiomyosarcoma, which are again thought to be fairly cold immune subtypes. So just really exciting to kind of see responses we hadn't expected in a very challenging group of tumors. Shannon Westin: We see all these patients and we have patients that respond so well to immunotherapy with other histotypes. And so it's so exciting to see an option for these really hard to treat tumors that our patients struggle with. So this is so, so very exciting. I wanted to make mention, you know, I was really impressed with the amount of translational work you were able to do in this early phase study. So do you want to review just maybe a few of the key findings that you guys discovered? Dr. Breelyn Wilky: It's always great. I'm a translational researcher at heart and we do a lot of immune correlative work. And I think the reason I got so excited about this field to begin with was trying to learn why it works for some patients and why it doesn't work for other patients. So I'm a huge believer in learning from every patient that we can. So it's such a testament to the company, Agenus, who sponsored this trial to invest their time and resources into correlative studies at this phase. It's huge. So we learned a couple of things. IL-6 or interleukin 6 is a cytokine that basically has, in other tumor types, been associated with worse outcomes. And what we were interested in this group is we saw the same thing. And again, sarcomas have very, very little correlative biology that's done. We're really in infancy and understanding the microenvironment and how that milieu balances out in our tumors. So we were really excited to see again that lower peripheral interleukin 6 associated with improved overall survival. So again, kind of sorting out a group of patients that might be immunologically favorable when it comes to this type of therapy. The other thing that's important to know about sarcoma is so the other tumor types are lucky and have PD-L1 expression and the tumor is a biomarker, but we never have PD-L1 expression. We can find it in sarcomas and it can be loosely correlated with a chance of benefit with immunotherapy. But I've had patients respond that were PD-L1 negative, and I've had patients that were loaded with PD-L1 that didn't seem to make a difference. And that's not just in this study. So we saw in this trial a trend towards improved overall survival with PD-L1 expression that wasn't significant, but there was like this trend. And it's really interesting because, again, this is largely a CTLA-4 directed therapy. And so what we wondered is if PD-L1 expression is an index of sort of this underlying potential immunogenicity. And actually PD-1 works very late in the whole immune process. That's really at the very end where you've got the T cell that's facing the tumor cell and it's just activating that T cell that's already grown up and already educated and ready to go. Whereas CTLA-4 is really educating in early immune responses and expanding the T cells that have potential to kill. So I'm interested to look into this in more depth in the future to see if this is actually the biomarker for CTLA-4 directed therapy that we've been looking for, because we really don't have a great sense about that. And then the last piece just to note is that in this trial, like most others, very, very few sarcomas had high mutational burden. Everybody was very low, which reflects the population. And it's just really more encouragement than an immune cold tumor with very crappy neoantigens can still respond to immunotherapy if we get them the right agents. Shannon Westin: Yeah, I mean, I'm taking notes because we have such a struggle with this across the gynecologic tumors. I'm like, “Okay, maybe this is finally it.” So hopefully your work will go on to really inspire us across a number of solid tumors that have been traditionally cold. So, so very exciting. And I would just say for my last question, obviously, congratulations on this successful study. What do you think are the next steps for this combination in sarcomas? Dr. Breelyn Wilky: So, again, just to your point, this trial enrolled a bunch of different subtypes, and sarcomas are not the only immune cold tumor that this combo has looked really promising for, microsatellite stable colorectal cancer, ovarian cancer that was platinum refractory, non-small cell lungs. So I think the future is really bright for immune cold tumors kind of across the board. So, yes, lots of hope for not just sarcomas but in terms of our patients, I just have to be so grateful to Agenus for their interest in a rare disease. Sometimes it's hard to get that interest for a very challenging group of patients that are all heterogeneous, they are not all the same and our big clinical trials are a few hundred patients. It's just a very different environment. But they have been so supportive and involved in making sure that sarcomas are represented in their priorities. So there are ongoing discussions about what the optimal way to explore this further in sarcomas is going to be and I cannot wait to have the official plans in place. But my hope is this will not be the last that we see of these drugs for our patients. Shannon Westin: Well, I support that and my vote is on your side. So, thank you so much again, Dr. Wilky. This time just flew by. This was such a great discussion and I mean, I think it's, again, a testament to your exciting data. And thank you to all of our listeners. This has been JCO After Hours' discussion of “Botensilimab (Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti-PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas,” published in the JCO on January 27, 2025. So be sure to check out the full manuscript. And we hope that you enjoyed this podcast. And if you want to hear more about research published in the JCO, check this out on our ASCO JCO 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. Dr. Wilky Disclosures  Consulting or Advisory Role: SpringWorks Therapeutics, Deciphera, Epizyme, Adcendo, Polaris, Boehringer Ingelheim, AADi, InhibRx Research Funding: Exelixis Travel, Accommodations, Expenses: Agenus    

Donald Trump's tariffs have headlined myriad news stories this week—including at BioSpace, where we reported Pfizer CEO Albert Bourla's claim that his company is prepared to reshore manufacturing if the president makes good on threats made last month. Eli Lilly also appears to be preparing, commiting $27 billion to boost its U.S. manufacturing capacity.   Meanwhile, another regulatory meeting has been canceled under new HHS Secretary Robert F. Kennedy Jr. Reuters revealed last week that an upcoming meeting of the FDA's external advisers for vaccine policy on March 13 has been canceled—just a week after the CDC Vaccine Advisory Board's first meeting of 2025 was postponed. Also on the policy front, BioSpace took a deep dive into priority review vouchers (PRVs) after Congress failed to reauthorize the rare pediatric disease PRV program at the end of 2024. Our reporting shows this will be painful for many biopharma companies who rely on funds from the sale of PRVs.   Speaking of money, AbbVie and Eli Lilly struck a pair of mid-size deals in hot spaces. AbbVie made a late obesity play this week, inking a licensing deal worth up to $2.2 billion with service provider Gubra to bring a long-acting amylin drug to the market, while Lilly hopped onto the hot molecular glue train, paying more than $1.2 billion in a licensing deal with Magnet Biomedicine.  Finally, we examined the somewhat lethargic immuno-oncology space, which has companies, including BMS, Roche, Summit Therapeutics and BeiGene, targeting TIGIT, VEGF, RAS and more in their quest to bring the next Keytruda—which led the way in 2024 as the world's best-selling drug—to the market.  

Black cumin, also known as black seed oil, is an ancient remedy that has a multitude of surprising benefits! I was very impressed to find it improves fungal overgrowth, thyroid health, cholesterol and more. I'll dive into 10 health benefits of black cumin plus offer my recommended protocols.   Watch more videos like this

In earlier clinical trials, the emerging gene therapy greatly reduced the treatment burden associated with injections of approved anti-VEGF therapies.

Dr. Lyudmila Bazhenova joins us again to share the newest changes to the living guideline on therapy for stage IV NSCLC without driver alterations. She discusses new evidence reviewed by the panel and changes to second-line recommendations for patients with good performance status and HER2 overexpression, and what these updates mean in practice. We discuss ongoing evidence generation as we await further updates to these living guidelines. Read the full living guideline update “Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2024.3” at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/living-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-02786     Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Lyudmila Bazhenova from University of California San Diego Moores Cancer Center, co-chair on “Therapy for Stage IV Non–Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2024.3.” It's great to have you back on the show today, Dr. Bazhenova. Dr. Lyudmila Bazhenova: It's my pleasure to be here as always. Brittany Harvey: Great. Then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the entire guideline panel, including Dr. Bazhenova, who has joined us here today, are available online with the publication of the guide in the Journal of Clinical Oncology, which is linked in the show notes. So then to dive into the content here, first, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer without driver alterations has frequent updates to the recommendations. What prompted this latest update? Dr. Lyudmila Bazhenova: Living ASCO guidelines are created to keep up with rapidly changing evidence which affect treatment of our patients with lung cancer. As a committee, we review published literature on a specific topic at the regular intervals and determine if it alters any recommendations. This time, upon our literature review, we felt that there are new data that requires an update in the guidelines and therefore the guidelines were updated. Brittany Harvey: Great. Thank you for that updated information. So then it looks like the panel updated recommendations for second line and subsequent treatment options for patients with good performance status and HER2 overexpression. What is that updated recommendation from the panel? Dr. Lyudmila Bazhenova: Yes, this is correct. We now added an extra recommendation for patients with stage IV non-small cell lung cancer who have overexpression of the protein called HER2. HER2 overexpression with 2+/3+ level via immunohistochemistry is seen in approximately 8% to 20% of patients with lung cancer. And the data behind our recommendation comes from the DESTINY-Lung01 trial where patients with HER2 overexpression were treated with trastuzumab deruxtecan. And we saw that if patients with stage IV non-small cell lung cancer had a HER2 IHC score of 3+, overall response rate was seen at 53% and median duration of response was 6.9 months and, therefore, that in our opinion qualified for updated recommendation. We are still waiting for additional results that will be released later on another clinical trial where we see preliminary data presented at the World Conference of Lung Cancer in 2024. They looked at 36 patients also with HER2 overexpression and saw the overall response rate of almost 45%. It is important to highlight in this smaller study that a majority of the patients in the study were actually having EGFR mutation and the response rate in those patients who had an EGFR mutation was higher than the response rate in patients without EGFR mutations who just had a HER2 overexpression. So for now this is updated in the guidelines, but we will wait for additional data or formal publication of a World Lung Conference presentation and see if those recommendations need to be changed. Brittany Harvey: Understood, and I appreciate you providing the context of some of those ongoing developments as well. So then what should clinicians know as they implement this updated recommendation? Dr. Lyudmila Bazhenova: Number one, we should all start from remembering to test for HER2 via immunohistochemistry. There is a slight difference in what considers HER2 positive in lung versus breast. In lung, we use what's called the gastric scoring and the difference is the circumferential versus non circumferential staining of the membrane. And number two, immunohistochemistry is not always included in next generation sequencing panels. So when you order your next generation sequencing, I think it's important to know if your company that you're using is testing for HER2 via immunohistochemistry. And if it's not, make sure that you find a company that does or work with your local pathology department to make sure that this testing is offered. It is also important to know the difference between HER2 overexpression and HER2 exon 20 insertion mutation even though the treatment for those two abnormalities is the same, which is trastuzumab deruxtecan. But the benefit that you can cite your patients and the rigor of the literature supporting the usage of trastuzumab deruxtecan in mutation versus overexpression is different. Brittany Harvey: Yes. And as you mentioned, it's essential that, in the first place, patients are actually receiving the testing so that we know if they're eligible for these treatment options. So what additionally does this change mean for patients with stage IV non-small cell lung cancer and HER2 overexpression? Dr. Lyudmila Bazhenova: So for patients, it adds another treatment modality which is now FDA approved. So if there are patients listening to me, make sure that your physician has tested your tumor for HER2 overexpression. So I think proactive asking of your physician would be very appropriate in this situation. Brittany Harvey: Absolutely. And then earlier you mentioned an ongoing trial that the panel was looking to for the future. But what other additional trials did the panel review during this guideline update and what is the panel examining for future updates to this living guideline? Dr. Lyudmila Bazhenova: So at this point we reviewed three additional studies. The results of those studies did not make it into a change in guidelines. So we reviewed the HARMONi-2 trial.  HARMONi-2 trial so far does not have an official publication and, as per our strategy on how we come up with ASCO guidelines, we need to wait for an official publication. So this is one thing we're going to be expecting in the future. Once this is published, we will review it and decide if we need to make an additional change in recommendations. For those of you who are not aware, HARMONi-2 trial used bispecific monoclonal antibody against VEGF and PD-1 and was a phase III randomized trial comparing their investigational product which is called ivonescimab over pembrolizumab for patients with PD-L1 more than 50. And again, we are waiting for the final publication to make our recommendation. The second trial we reviewed was a LUNAR trial and the LUNAR trial looked at addition of tumor treating fields to chemotherapy or immunotherapy in patients whose cancer progressed with platinum doublet. The key point about this study is that immunotherapy was not required to be administered in a first line setting which is a current standard of care in the United States. And even though the study met their primary endpoint of overall survival, there were more benefits in patients who were immunotherapy naive in the second line. And we felt that given the potential lifestyle implication of wearing a device for 18 hours per day, and the lack of evidence in immunotherapy-pretreated population, and the absence of data in the first-line setting where we currently using immunotherapy in the United States, we felt that there is insufficient data to definitely recommend addition of tumor treating fields to systemic chemotherapy for most patients. And we are waiting for additional trials that are ongoing in this setting to formalize or change our recommendations. And we also reviewed- the final study that we reviewed was TROPION-Lung01. TROPION-Lung01 study was a phase III study in post platinum doublet setting which compared efficacy of Dato-DXd and docetaxel and trials showed improvement in progression free survival but not in overall survival. And progression free survival benefit was more pronounced in non-squamous carcinoma histology subgroup and we felt that the results do appear promising, but the strength of evidence which was based on unplanned subgroup analysis was not sufficient enough to make a change in treatment recommendation at this time. Brittany Harvey: I appreciate your transparency on why some of that data did not prompt a change to recommendations at this time. And additionally, we'll look forward to those future published results and potential incorporation of new data into future versions of this living guideline. So, I want to thank you so much for your work to rapidly and continuously update this guideline and for your time today, Dr. Bazhenova. Dr. Lyudmila Bazhenova: It is my pleasure. Thank you so much. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast. To read the full guideline, go to www.asco.org/living-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the  Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.   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.  

Dr. Jyoti Patel is back on the podcast to discuss the updates to the living guideline on therapy for stage IV NSCLC with driver alterations. She shares updated recommendations in the first- and second-line settings for patients with stage IV NSCLC and classical EGFR mutations, and the impact of these updates for clinicians and patients. We also look to the future to discuss ongoing developments in the field. Read the full living guideline update “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.3” at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/living-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-02785     Brittany Harvey: Welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows including this one at asco.org/podcasts.   My name is Brittany Harvey and today I'm interviewing Dr. Jyoti Patel from Northwestern University, co-chair on “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.3.” It's great to have you back on the show today, Dr. Patel. Dr. Jyoti Patel: Thanks so much. Happy to be here. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Patel, who has joined us here today, are available online with the publication of the guideline and in the Journal of Clinical Oncology, which is linked in the show notes. So then, to dive into the content of this update, Dr. Patel, this clinical practice guideline for systemic therapy for patients with stage IV non small cell lung cancer with driver alterations is living, meaning that it's continuously reviewed and updated. So what data prompted this latest change to the recommendations? Dr. Jyoti Patel: Thanks so much. So it's really been an exciting time in the treatment of EGFR lung cancer, particularly this past year has required us to rethink approaches to front- and second-line therapy. In this particular update, we examined what patients in the front-line setting may be offered by their clinicians. And so we're talking about the population of classical EGFR mutations, so exon 19 and exon 21 L858R substitution. And so certainly for this population, osimertinib has a high level of evidence and should be offered to all patients at the time of diagnosis when they present with advanced disease. Our last update included a recommendation that patients could also get platinum doublet chemotherapy with osimertinib or osimertinib alone. This current recommendation also introduces another alternative therapy and that's the combination of amivantamab plus lazertinib. And so now, clinicians are faced with three really good options for their patients with EGFR exon19 deletion or L858R. Brittany Harvey: It's great to hear that there's this advance in the space, particularly for patients with these classical EGFR mutations that you mentioned. So what should clinicians know as they implement these new first-line recommendations? Dr. Jyoti Patel:  I think it's become more complex than ever. Certainly, we know again that patients should get osimertinib in the frontline setting. But we've been kind of stuck at progression-free survival that's between a year and a half and two years. And so we've really been looking at opportunities to intensify therapy. So one could certainly be with chemotherapy or switching over to amivantamab, the bispecific antibody that targets EGFR and MET plus lazertinib, an oral TKI that's very similar in structure to osimertinib. And when you're talking to a patient, it's really a conversation about balancing efficacy with toxicity. Unfortunately, as we know, there aren't that many free lunches. And so if we think about what a patient is hoping for in their therapy and how we can further personalize treatment options, really is important to look at some of the analyses for this study. So in the study of amivantamab plus lazertinib, we know that there were increased toxicities with a combination of both therapies. In fact, up to 75% of patients had over grade 3 toxicities, versus about 43% of patients with osimertinib monotherapy. And we know if we look back at FLAURA2, almost two thirds of patients with osimertinib and chemotherapy had grade 3 toxicities, compared to 27% of patients with osimertinib alone. So we certainly see an increase in toxicities. Then we have to ask ourselves, are those paper toxicities or ones that really impact patients? And we know that amivantamab, for example, causes significant cutaneous toxicities. With both of these therapies, whether it's chemotherapy or adding amivantamab, there's the burden of infusional visits and increased time in the doctor's office. Certainly with chemotherapy, there can be an increased incidence of myelosuppression. And so when we're thinking about advising our patients, certainly we need to talk about the toxicities. But one thing that we've been able to do is to look at the patients that were included in this trial. And what we really find is that in higher risk cohorts, particularly those that we know historically have done less well with standard osimertinib, so patients, for example, with CNS metastasis, for those patients with co-mutations, it may be that that additive benefit is significant. And so one example I think would be from the MARIPOSA study, again, the study of amivantamab and lazertinib versus chemotherapy. What we can say is that patients who had co-mutations, so patients with EGFR mutations as well as TP53, lazertinib and amivantamab led to a hazard ratio of 0.65 compared to osimertinib alone. So that was 18.2 months versus 12.9 months. And so this may be really important to patients. And we also see conversely that patients with wild type TP53, so those patients who didn't have the mutation, probably had equivalent survival regardless of therapy. So certainly, we need to prospectively study some of these high-risk cohorts. We've only seen progression-free survival in these studies. And so at this juncture, we can advise our patients about toxicity, the improvements in certain categories of progression-free survival, but we really still don't know how this pans out in overall survival. In many of these studies, all patients do not necessarily cross over to the study arm and so they may have lost the benefit of subsequent therapy. Brittany Harvey: Absolutely. It's very important to talk about that balance of benefits and risks and particularly those toxicities that you discussed. So I appreciate reviewing that recommendation and the considerations for clinicians for first-line therapy. This update also included a second-line treatment update. What is that update for patients with EGFR alterations? Dr. Jyoti Patel: So this is where it gets super tricky because we have a frontline option with amivantamab and now we've had an update in the second line option. So what we said is that for patients who have progressed on an EGFR TKI, and in the United States, certainly that's predominantly osimertinib, or those in other parts of the world that may have gotten an earlier generation TKI, but do not have evidence of T790M or other targetable mutations, we can offer patients chemotherapy with or without amivantamab. And so certainly we have seen that this again leads to improved survival. There have also been a number of studies looking at incorporation of PD-L1 and anti-VEGF therapies. And what we can say, I think pretty clearly is that multiple phase 3 trials have really shown no benefit of the addition of PD-1 to platinum chemotherapy. But there are some emerging bispecific antibodies that may target PD-1 as well as VEGF, or combinations of antibodies that target both of those pathways that may improve outcome. At this juncture, I think we feel that the evidence surrounding chemotherapy plus amivantamab is strongest, but there is certainly work in this space that will be of interest. Now, what happens if your patient received amivantamab and lazertinib in the frontline setting and then has progression? And so we're trying to understand resistance mechanisms and opportunities for treatment. What the panel decided to recommend, based on the available evidence, was that certainly those patients should get platinum-based chemotherapy, but there may also be a role for antivascular endothelial growth factor targeting therapy such as bevacizumab in patients in whom it would be safe. Brittany Harvey: Great. I appreciate you detailing those recommendations when it gets complicated in the second-line setting. So what should clinicians know as they implement these second-line recommendations too? Dr. Jyoti Patel: So certainly the frontline setting matters significantly. So if a patient gets osimertinib in the frontline setting, we generally suggest that patients undergo repeat testing to see if they have another targetable mutation. If they don't, then I think preferred therapy would be chemotherapy with or without amivantamab. And amivantamab leads to a significant improvement in progression-free survival and response rate at the cost of increased risk of toxicity. For patients who get FLAURA2 in the frontline setting, chemotherapy plus osimertinib, it's a little bit of an unclear space. Those patients most likely would get docetaxel with or without ramucirumab. But there are other agents that we hope to have available to our patients in the near future. For patients who receive amivantamab and osimertinib, we recommend that those patients get chemotherapy probably with anti-VEGF as demonstrated by multiple trials that have shown the improved progression-free survival with introduction of an anti-VEGF agent. And we've seen evidence of amivantamab in the third line setting, so it is likely that this question about sequencing really takes center stage in our next set of trials. When you're talking to a patient, I think again, it's absolutely important to discuss: What are their goals? How symptomatic or how fast is their progression? Are there ways in which patients may benefit from spot treatment oligoprogression such as radiation? When is the right time for introduction of amivantamab and when do we think patients need chemotherapy? Is it up front or predominantly in the second-line setting? Brittany Harvey: Definitely. And then you've just touched on the goals of treatment for individual patients. So in your view, what does this update mean for patients with stage IV non-small cell lung cancer and an EGFR alteration? Dr. Jyoti Patel: For patients, this is a time in which shared decision making really needs to take center stage. So our best patients are those patients that are best informed not only about their disease but also have a good understanding about what is important to them and their families in terms of care. And so bringing that shared understanding to the table again helps us think about this particular cancer as more of a journey rather than just a one off treatment. Therapy will hopefully be prolonged, and so it's absolutely important that we address toxicities, make therapies more tolerable, again, with the shared goal of living long and living well. Brittany Harvey: Absolutely. Those are key points to making sure that patients are living both longer and have a good quality of life during that time as well. So then, before you mentioned the possibility of future sequencing trials and other ongoing developments. What additional studies or future directions is the panel examining for future updates to this living guideline? Dr. Jyoti Patel: So certainly we're thinking about trials that look at, for example, cfDNA clearance. So are there patients that do well and can we detect that early on without having to intensify therapy on day 1 so it may be that we add chemotherapy a little bit later. I think really exciting are some of the new bispecific. The HARMONi-A trial was a trial in China of a novel bispecific, ivonescimab. And this drug targets both PD-1 and VEGF and it was combined with chemotherapy. And this trial found almost a doubling of progression-free survival with this drug in combination chemotherapy in an EGFR patient population. That study is being planned and being run in the United States to see if we have similar outcomes with a more diverse population. So certainly that's exciting. There are a number of antibody drug conjugates that are being studied in the post-chemotherapy setting as well. And I think we'll likely soon see a better understanding of what co-mutations and burden of disease really mean when we're thinking about assigning treatment. So which patients, again, need intensification of therapy and which patients may do really well on just an oral agent that they're taking at home with more tolerable toxicity than dual treatment. Brittany Harvey: Yes, we'll look forward to continued developments in these fields and seeing some of those studies come to fruition. So with that, I want to thank you for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Patel. Dr. Jyoti Patel: Thanks so much, Brittany. It's really an exciting time for lung cancer and we hope that these updates really help physicians decide the best treatments for their patients. Again, it's a rapidly evolving landscape which is fantastic, but it does become more cumbersome to stay ahead of the literature. Brittany Harvey: Definitely. And so we appreciate your time and the panel's time spent reviewing this literature and providing this much needed information to clinicians everywhere. So finally, thank you to all of our listeners for tuning into the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/living-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the  Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.   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.  

Jeffrey Meckler, CEO of Indaptus Therapeutics, is focused on using their decoy platform to activate the immune system to fight cancer and infections. This approach activates the innate and adaptive pathways in a controlled manner using a short-term pulsed dosing regimen and helps avoid the toxicity issues seen in other immunotherapies. The therapy is cleared from the system quickly, allowing the immune system to be modulated and potentially used with other cancer treatments. Jeffrey explains, "It's a very uncommon approach because we have, over the last several decades, really had a paradigm for treating cancer in immunotherapy, and that paradigm is turning one or a couple switches in the immune system to help fight the cancer. Again, as I mentioned before, the concept of doing too much, activating too much comes from this idea that you'll hit toxicities and, like I said, cytokine storm or whatever. What we do is go about it in a way that people are coming to. The big talk right now are these VEGF PD-1 bispecific antibodies and what they're actually doing. Part of this is that the VEGF activates innate immune pathways. The PD-1 activates adaptive immune pathways." "So there's a lot of talk about what's been going on with Summit Therapeutics, and everybody now is doing these VEGF PD-1. We're even broader than that. And more importantly, we're also in a short burst. We call our therapy pulse prime, but it's cleared in the system within a couple of hours. So it does this activation, but instead of keeping the foot on the accelerator the entire time, it lets up. And what we started doing is giving it weekly, and our preclinical models show that weekly administration in combination with other therapies is the most potent approach for us."  #IndaptusTherapeutics #Decoy20 #Biotech #Cancer #CancerResearch #Immunotherapy #LungCancer #BladderCancer #LiverCancer #PancreaticCancer #ColonCancer indaptusrx.com Download the transcript here

Jeffrey Meckler, CEO of Indaptus Therapeutics, is focused on using their decoy platform to activate the immune system to fight cancer and infections. This approach activates the innate and adaptive pathways in a controlled manner using a short-term pulsed dosing regimen and helps avoid the toxicity issues seen in other immunotherapies. The therapy is cleared from the system quickly, allowing the immune system to be modulated and potentially used with other cancer treatments. Jeffrey explains, "It's a very uncommon approach because we have, over the last several decades, really had a paradigm for treating cancer in immunotherapy, and that paradigm is turning one or a couple switches in the immune system to help fight the cancer. Again, as I mentioned before, the concept of doing too much, activating too much comes from this idea that you'll hit toxicities and, like I said, cytokine storm or whatever. What we do is go about it in a way that people are coming to. The big talk right now are these VEGF PD-1 bispecific antibodies and what they're actually doing. Part of this is that the VEGF activates innate immune pathways. The PD-1 activates adaptive immune pathways." "So there's a lot of talk about what's been going on with Summit Therapeutics, and everybody now is doing these VEGF PD-1. We're even broader than that. And more importantly, we're also in a short burst. We call our therapy pulse prime, but it's cleared in the system within a couple of hours. So it does this activation, but instead of keeping the foot on the accelerator the entire time, it lets up. And what we started doing is giving it weekly, and our preclinical models show that weekly administration in combination with other therapies is the most potent approach for us."  #IndaptusTherapeutics #Decoy20 #Biotech #Cancer #CancerResearch #Immunotherapy #LungCancer #BladderCancer #LiverCancer #PancreaticCancer #ColonCancer indaptusrx.com Listen to the podcast here

On this week's episode, Daphne Zohar, Paul Matteis, Brian Skorney, Tim Opler and Abe Ceesay kick off with a more optimistic yet cautious perspective that investor sentiment may be improving. The group notes positive market trends post-JPM with the XBI index rising from 86.5 to around 92 since early January. The discussion also touches on on the re-emergence of wall cross pipes and the impact on generalist investor interest. The hosts discuss the positive M&A outlook for 2025, noting Intra-Cellular's recent acquisition by J&J. Staying on the neuro theme, GH Research announced impressive data from its Phase 2b trial for a short-acting psychedelic drug for treatment-resistant depression. This extended into a discussion on the broader implications of neuropsych drug development, including the need for experienced management and the challenges of patient selection and managing high placebo responses. Other topics discussed include FDA's approval of Axsome's migraine drug, the anti-VEGF therapy competitive dynamics, Trump's tariffs, and more. This episode aired on February 7, 2025.

Welcome to BFR Radio, and Happy New Year!

Welcome to another episode of the Oncology Brothers podcast! In this episode, Drs. Rahul and Rohit Gosain are joined by Dr. Pashtoon Kasi from City of Hope to discuss the management of side effects associated with key treatments utilized in colorectal cancer, but also in other tumor types.  We dived deep into two important drug classes: Bevacizumab, an anti-VEGF antibody, and the anti-EGFR antibodies, Panitumumab and Cetuximab. Dr. Kasi provided a comprehensive overview of these targeted therapies, their mechanisms of action, and the common side effects that patients may experience. Key topics covered in this episode included: •⁠  ⁠Overview of Bevacizumab and its side effects, including hypertension, proteinuria, and risk of bleeding. •⁠  ⁠Clinical pearls for managing side effects associated with Bevacizumab. •⁠  ⁠Discussion on the skin toxicities, nail changes, and electrolyte imbalances related to Panitumumab and Cetuximab. •⁠  ⁠The importance of preemptive strategies in managing skin rashes and other side effects. •⁠  ⁠Insights into infusion reactions with Cetuximab and considerations for patient safety. Join us for this informative discussion that aims to enhance your understanding of these critical therapies and improve patient outcomes.  Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers Don't forget to check out our other episodes in the Tox Check series, where we explore antibody-drug conjugates and CAR T therapies. Subscribe to our channel for more insights on oncology treatments and patient care!

For decades now, we have been able to offer anti-VEGF treatments to patients with wet AMD.  Yet for dry AMD, there have been few options we can recommend to our patients outside of AREDS formulations and lifestyle modifications.  But with newer scientific advances, there are indeed new classes of injectable medications that are now being offered to some patients wtih dry AMD.  Retinal specialist Dr. Ashkan Abbey joins the podcast to share the latest research. This episode is sponsored by Thea Pharma Canada - https://www.theapharma.ca Become a supporter of this podcast: https://www.spreaker.com/podcast/blind-spot-the-eye-doctor-s-podcast--5819306/support.

In this episode, I discuss how different forms of exercise impact brain health and performance in both the short and long term. I explain how many of the positive effects of exercise on brain function occur through the action of specific neurochemicals that increase alertness. I also cover how to best time exercise and which specific types of exercise to include in your weekly routine to maximize benefits for your brain. Additionally, I explain how certain types of exercise trigger the release of a hormone from your bones called osteocalcin, as well as brain-derived neurotrophic factor. Together, these substances increase neuroplasticity and enhance learning. The positive effects of exercise on brain oxygenation, blood supply, and fuel utilization are also discussed. Listeners will learn how to design a weekly exercise program that optimizes physical fitness, brain health, longevity, and performance, along with the mechanistic logic behind those recommendations. Find show notes with articles, resources and more at hubermanlab.com. Pre-order Andrew's upcoming book, Protocols: https://go.hubermanlab.com/protocols Thank you to our sponsors AG1: https://drinkag1.com/huberman BetterHelp: https://betterhelp.com/huberman Helix Sleep: https://helixsleep.com/huberman David: https://davidprotein.com/huberman Function: https://functionhealth.com/huberman Maui Nui: https://mauinui.com/huberman Timestamps 00:00:00 Exercise, Brain Health & Performance; Protocols Book 00:04:03 Sponsors: BetterHelp & Helix Sleep 00:06:55 Brain Health, Cardiovascular & Resistance Training 00:11:51 Exercise & Positive Impact on Brain Performance; Arousal 00:18:20 Learning & Arousal 00:23:18 Sponsors: AG1 & David 00:26:01 Exercise & Acute Learning 00:29:16 Tool: High-Intensity Training & Cognitive Flexibility; Over-Training 00:33:32 Long-Term Brain Health; Tool: Exercise “Snacks”, Cognitive Performance 00:36:57 Exercise, Brain & Body Energy, Adrenaline, Norepinephrine 00:44:08 Adrenal “Burnout”?; Exercise to Increase Energy, Adrenaline 00:48:20 Tool: Core, Compound Movements; Mind-Body Connection 00:53:58 Sponsor: Function 00:55:45 Bones, Osteocalcin, BDNF & Hippocampus; Tool: Jump Training 01:01:30 Exercise, Fuel, Multifactorial Pathways; BDNF & Activity 01:05:06 Lactate, Astrocytes & Brain Function; VEGF & Brain Health 01:11:17 Tools: Zone 2, High-Intensity Training, Time Under Tension Training 01:19:54 Sponsor: Maui Nui 01:21:37 Tools: Time Under Tension; Explosive Jumping, Eccentric Control Training 01:25:30 Injury & Exercise, Illness 01:28:09 Sleep; Injury, Sleep-Deprivation & Exercise 01:33:51 SuperAgers, Anterior Mid-Cingulate Cortex, Grit & Persistence 01:42:04 Tool: Embrace Challenges; Deliberate Cold Exposure, Rope Flow 01:47:39 Zero-Cost Support, YouTube, Spotify & Apple Follow & Reviews, Sponsors, YouTube Feedback, Protocols Book, Social Media, Neural Network Newsletter Disclaimer & Disclosures

Experts provide an overview of current systemic treatment options for 1st line uHCC, discussing the role of IO and IO-based combinations, along with emerging therapies and the latest clinical data.   Topics also include:  • Efficacy and safety of IO and IO combinations in HCC • How to select between the two 1st-line IO-based treatment options based on clinical factors • Future treatment in unresectable HCC   Clinical Takeaways • Two 1st-line IO and IO-based combinations are approved for patients with unresectable hepatocellular carcinoma (HCC), with ongoing advancements shaping the treatment landscape • Clinical trials in newly diagnosed unresectable HCC patients have validated the effectiveness of IO plus anti-VEGF (atezolizumab + bevacizumab, IMbrave150) and dual IO (tremelimumab + durvalumab, HIMALAYA) approaches, establishing the proof of principle for these strategies • Landmark analysis is critical in IO-based treatments due to the delayed and continued separation of survival curves. Notably, the STRIDE regimen (single tremelimumab regular interval durvalumab) shows one in five patients achieving five-year survival in long-term follow-up • IO and IO-based regimens for unresectable HCC are generally well-tolerated, with immune-related adverse effects manageable using steroids when necessary • In clinical practice, treatment choice should be individualised, taking into account factors such as potential side effects and logistical considerations, including the frequency of hospital visits   Website: http://www.oncbrothers.com/ X/Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

Please visit answersincme.com/GCB860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, experts in the management of diabetic macular edema (DME) discuss the primary care physician (PCP) and ophthalmologist's partnership in the care for patients with DME and optimizing treatment with VEGF-targeting agents. Upon completion of this activity, participants should be better able to: Explain how extending treatment intervals for DME can improve patient satisfaction and treatment persistence with intravitreal anti-VEGF therapy; Discuss the clinical benefits of longer-acting intravitreal anti-VEGF agents in the treatment of DME; Describe multidisciplinary care plans that improve the long-term treatment outcomes of patients with patients with DME; and Outline strategies for optimizing DME outcomes in the primary care setting. This activity is intended for US healthcare professionals only.

Giving Robert F. Kennedy Jr. control of HHS would be disastrous, argues Washington Editor Steve Usdin on the latest BioCentury This Week podcast. Expanding on his Editor's Commentary, Usdin explains why Kennedy would be an unmitigated disaster for FDA, NIH and CMS, for companies that research, develop and manufacture medicines and for people around the world who rely on those companies and agencies. He calls on biopharma leaders to speak out and affirm basic truths, even if it puts them in harm's way.BioCentury's Lauren Martz gives her take on why new data for Blenrep belantamab mafodotin — an oncology therapy withdrawn two years ago — help make the case for introducing new experimental therapies such as the antibody-drug conjugate from GSK earlier in the course of treatment.And Paul Bonanos and his editorial colleagues discuss the recent bolus of West-East deals, including two around anti-PD-(L)1 x VEGF bispecifics: the acquisition of Biotheus by BioNTech for $800 million up front, and the licensing of global rights by Merck & Co. to a program from LaNova Medicines for $588 million. Monday's Deals Report in BioCentury captures three more deals for China bispecifics.View full story: https://www.biocentury.com/article/65423300:00 - Introduction01:12 - RFK Jr. & HHS13:15 - Blenrep's Comback19:25 - China DealsTo submit a question to BioCentury's editors, email the BioCentury This Week team at podcasts@biocentury.com.Reach us by sending a text

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Merck has committed up to $3 billion in a deal with Lanova Medicines focused on PD-1/VEGF. The deal comes as Merck faces competition from Bristol Myers Squibb in leukemia, leading Allogene to end phase I enrollment. Analysts view Merck's move as conservative, despite recent excitement around PD-1/VEGF. In other news, GSK is making a case for Blenrep in multiple myeloma, while Adaptimmune plans to submit a rolling BLA for its sarcoma cell therapy. PTC has received the first FDA approval for direct-to-brain gene therapy. Additionally, Marinus Pharmaceuticals has laid off 45% of its employees. Transitioning to other topics, we also cover Biogen's stock performance, a significant deal in the CDMO sector, and recent developments in the pharmaceutical industry.

Join me and Dr. John Lewis, Founder and President of Dr Lewis Nutrition, as we dive deep into the fascinating world of polysaccharides. We're breaking down the myths about sugars and exploring how plant-based diets truly impact your health.  We'll also compare plant and animal proteins, clear up some common misconceptions about nutrients, and talk about what really matters when it comes to staying healthy—like nutrition, exercise, and sleep. This episode is packed with practical insights to help you make better choices for long-term health, so don't miss it! Key Takeaways: Polysaccharides like those found in aloe vera and rice bran are potent health-promoting substances, distinct from simple sugars notorious for spiking insulin and metabolic issues. Dr. John Lewis's groundbreaking research supports the use of a polysaccharide-based dietary supplement to improve cognitive and immune function in individuals with moderate to severe Alzheimer's disease. A plant-based diet offers crucial nutrients, casting doubt on the perceived necessity of animal proteins for sufficient nutrition. The mechanisms of aloe vera—notably its acute polysaccharide content—underpin its centuries-old reputation for soothing burns and other wounds. Dr. Lewis advocates for a holistic approach to health, encompassing plant-based diets, strategic supplementation, regular exercise, and adequate sleep.   More of  Dr. John Lewis: Dr. John E. Lewis has spent most of his career developing a unique approach as someone who “walks the walk” through all of his combined professional and personal experiences to attaining optimal health through nutrition, dietary supplements, and exercise. Throughout his research career, he has evaluated many different nutritional approaches to enhancing well-being, particularly for brain health, immune function, and counteracting aging. He can separate fact from fiction regarding how to utilize nutrition and dietary supplements to help you achieve and maintain optimal health. If you need a trusted source of information, products, and services, then look no further than Dr. Lewis and how he can help you achieve your health-related goals. Professional Career Dr. Lewis is past full-time Associate Professor in the Department of Psychiatry and Behavioral Sciences at the University of Miami Miller School of Medicine and the Founder and President of Dr Lewis Nutrition™. He is a Diplomate, Faculty Member, and Advisor of the Medical Wellness Association. He has been the principal investigator of over 30 different studies on human health in his research career. During that time, he either directly raised or indirectly supported raising over $23 million in grants, gifts, and contracts for research studies and clinical trials and educational programs for medical students. In addition to his research, Dr. Lewis has been an invited national and international lecturer and guest speaker at conferences and as a guest on television shows. He is a well-known author with over 180 peer-reviewed publications in some of the world's leading scientific journals. He has also mentored many different students, from undergraduates to post-doctoral trainees, in not only how to conduct clinical research but to apply the principles of health promotion into daily practice. Research Interests Much of Dr. Lewis's research has focused on evaluating the effects of nutrition, dietary supplements, and exercise on various aspects of human health. He and his colleagues have been continually searching for ways to help people achieve and maintain health through natural treatments that align with our physiology. A primary stimulus for the origin of Dr Lewis Nutrition™ occurred after Dr. Lewis ran his landmark study on how an aloe polysaccharide multi-nutrient complex improved cognitive and immune functioning after 12 months in persons with moderate to severe Alzheimer's disease, leading to the creation of the dietary supplement, Daily Brain Care. Daily Brain Care showed clinically and statistically significant improvements in cognition according to the ADAS-cog cognition score and statistically significant improvements in inflammation (according to TNFα and VEGF), immune function (according to the CD4/CD8 ratio), and adult stem cells (according to CD14+ cells). His seminal publication from the study in the Journal of Alzheimer's Disease not only spurred him to leave academics and pursue a science-based business career, but also enabled him to be selected for a widely-acclaimed TEDxMiami talk. Website Instagram   Connect with me!: Website Instagram Facebook YouTube

Drs. Katherine Talcott and Yoshihiro Yonekawa join to discuss four recent publications in major ophthalmology journals.Featured articles:Anti-VEGF or PRP First for PDR (https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2822892)Face Down Positioning for Macular Holes (https://www.aaojournal.org/article/S0161-6420(24)00483-4/fulltext)Management of Post-Cataract Endophthalmitis (https://www.ophthalmologyretina.org/article/S2468-6530(24)00337-3/abstract)PDS Clinical Trial Results (https://www.ophthalmologyretina.org/article/S2468-6530(24)00400-7/fulltext)ReferenceMichels Retinal Detachment (referenced in podcast, https://www.amazon.com/Retinal-Detachment-Ronald-G-Michels/dp/0801634172)Relevant Financial Disclosures: Dr. Sridhar and Dr. Talcott have consulted for Apellis and Iveric.You can claim CME credits for prior episodes via the AAO website. Visit https://www.aao.org/browse-multimedia?filter=Audi

In this episode of the New Retina Radio Journal Club with VBS, Maura Di Nicola, MD; Sruthi Arepalli, MD, and Barton Blackorby, MD, discuss a recent study comparing endophthalmitis rates following anti-VEGF injections with pre-treatment using either 5% Povidone Iodine or 0.05% Chlorhexidine. They highlight how prefilled syringes can reduce the risk of endophthalmitis and explore the implications for clinical practice, including antiseptic protocols, patient sensitivities, and how to navigate conflicting study outcomes. Tune in for valuable insights that could influence your injection protocols.

Drs. Safa Rahmani and Katherine Talcott join the podcast to preview the October 2024 edition of Retinal Physician, found online at http://www.retinalphysician.com. The theme for this issue was clinical trials and anti-VEGF therapy.Relevant Financial Disclosures: Dr. Sridhar has consulted for Eyepoint, Genentech, and Regeneron.You can claim CME credits for prior episodes via the AAO website. Visit https://www.aao.org/browse-multimedia?filter=Audi

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

Too busy to read the Lens? Listen to our weekly summary here! In this week's episode we discuss: A dexamethasone intracanalicular insert may provide a dropless treatment alternative for dry eye. MYL-1701P, a biosimilar to aflibercept, had similar efficacy, safety and immunogenicity in diabetic macular edema. Psoriasis was found to be an independent risk factor for developing neovascular AMD in diabetic patients. While IV methylprednisolone led to greater decreases of TSH antibody in the first 3 months, levels did not differ from no treatment controls at 12 months. A new study explores two-year efficacy & safety profiles of different anti-VEGF regimens for neovascular age-related macular degeneration.

Tired of not having good treatment options available for Hashimoto's? If so, I have some good news for you. Outside of traditional treatments like thyroid medication, there are some incredibly powerful natural options that have been shown in some research studies to help. One of the most potent is known as nigella sativa. I'm going to use nigella sativa and black seed oil almost interchangeably in this video but here's the difference: Nigella sativa is the plant that produces black seeds and black seeds can be cold pressed to produce black seed oil. The active ingredients in nigella sativa can be found in both black seeds and black seed oil so it's very likely that taking any of these 3 may provide benefits. One study that looked at nigella sativa found the following: 1. It had a pro-thyroid benefit and acted to help reduce TSH levels and increase free thyroid hormone levels. 2. It had a thyroid-antibody-reducing benefit and resulted in a decrease in TPO antibodies by almost 50%. 3. It may provide an anti-thyroid cancer benefit by reducing VEGF levels. These results are incredible and should perk the interest of just about every patient with Hashimoto's. The study referenced here used nigella sativa at 2 grams per day but I think black seed oil can provide superior benefits. Download my free thyroid resources here (including hypothyroid symptoms checklist, the complete list of thyroid lab tests + optimal ranges, foods you should avoid if you have thyroid disease, and more): https://www.restartmed.com/start-here/ Recommended thyroid supplements to enhance thyroid function: - Supplements that everyone with hypothyroidism needs: https://bit.ly/3tekPej - Supplement bundle to help reverse Hashimoto's: https://bit.ly/3gSY9eJ - Supplements for those without a thyroid and for those after RAI: https://bit.ly/3tb36nZ - Supplements for active hyperthyroidism: https://bit.ly/3t70yHo See ALL of my specialized supplements including protein powders, thyroid supplements, and weight loss products here: https://www.restartmed.com/shop/ Want more from my blog? I have more than 400+ well-researched blog posts on thyroid management, hormone balancing, weight loss, and more. See all blog posts here: https://www.restartmed.com/blog/ Prefer to listen via podcast? Download all of my podcast episodes here: https://apple.co/3kNYTCS Disclaimer: Dr. Westin Childs received his Doctor of Osteopathic Medicine from Rocky Vista University College of Osteopathic medicine in 2013. His use of “doctor” or “Dr.” in relation to himself solely refers to that degree. Dr. Childs is no longer practicing medicine and does not hold an active medical license so he can focus on helping people through videos, blog posts, research, and supplement formulation. To read more about why he is no longer licensed please see this page: https://www.restartmed.com/what-happened-to-my-medical-license/ This video is for general informational, educational, and entertainment purposes only. It should not be used to self-diagnose and it is not a substitute for a medical exam, treatment, diagnosis, prescription, or recommendation. It does not create a doctor-patient relationship between Dr. Childs and you. You should not make any changes to your medications or health regimens without first consulting a physician. If you have any questions please consult with your current primary care provider. Restart Medical LLC and Dr. Westin Childs are not liable or responsible for any advice, course of treatment, diagnosis, or any other information, services, or product you obtain through this website or video. #thyroid #hypothyroidism #hashimoto's

Does switching long-term wet AMD patients to faricimab (Vabysmo, Genentech/Roche) result in meaningful change to disease presentation? Join New Retina Radio Journal Club host Ben Young, MD, MS, and panelists Lediana Goduni, MD, and Josh Uhr, MD, as they break down a recent real-world study published in the literature. After the break, they review whether the study's findings could inform clinical decision-making, weigh the value of anatomic improvement that doesn't result in significant improvement in vision quality, and review their comfort with switching from legacy anti-VEGF agents to next-generation therapies.

Drs. Maura Di Nicola and Basil Williams join host Dr. Jay Sridhar to discuss the latest ongoing ocular oncology clinical trials for the treatment of uveal melanoma and associated complications of radiation therapy. Their review begins with the DRCR Retina Network's Protocol AL, which is studying the use of anti-VEGF agents or corticosteroids to reduce the occurrence of radiation retinopathy and consequent vision loss. Drs. Di Nicola and Williams also offer insights about the use of Belzupacap Sarotalocan (Bel-sar) for early-stage choroidal melanoma (CoMpass trial), as well as adjuvant treatment with darovasertib, a protein kinase C inhibitor. For all episodes or to claim CME credit for selected episodes, visit www.aao.org/podcasts.

There are incredible non-invasive or minimally invasive techniques to restore joint health and avoid surgery. We will explore Dr. Bianco's path and experience in this amazing field of joint restoration and offer you simple steps that you can engage to ease pain.Upfront summary: 1. Modern technology such as stem cells and exosomes allow us to accomplish results that weren't available 10 years ago.2. You can rebuild, restore and regenerate joint health in ways that surgery cannot, such as restoring cartilage. 3. Everyone over the age of 50 has some degree of arthritis but not everyone feels pain. Having arthritis and having pain are not synonymous.4. We are going to discuss the differences between these injection therapies:· PRP – Platelet Rich Plasma, an older technology using your own growth factors.· Stem cells & exosomes offer a huge magnitude of difference over PRP and supply true healing power.· Prolotherapy – stimulates the body's natural repair process.· Ozone stimulates 3 modes of action: mitochondrial energy, detoxification, and immune system stabilization and support. It also works to animate stem cells for repair.5. Adjuncts that support and amplify these injection therapies:· Peptides – BPC-157 is a natural occurring protein that stimulates a sharp rise in repair molecules VEGF, Factor VIII, collagen, and CD34.· Glucosamine & Chondroitin – stimulates chondrocytes to generate new cartilage and create hyaluronic acid for lubrication.· MSM – antioxidant and anti-inflammatory, makes cartilage stronger.· Boswellia & Curcumin – reduce inflammation like NSAIDS but without the side effect and danger.· Joint & Body Collagen (HippEvo) – Fortigel and Tendoactive are proven elements to strengthen joints and reduce inflammation.· Hyperbaric Oxygen chamber at Huber Personalized Medicine – doubles the speed of repair for a quicker return to action. · Red light laser therapy – mitochondrial stimulation to augment repair energy

In this episode, we sit down with Dr. John Lewis, a leading expert in nutritional research and the therapeutic potential of Aloe polysaccharides. Dr. Lewis shares insights from his groundbreaking studies on Alzheimer's disease, multiple sclerosis (MS), and the broader impacts of Aloe polysaccharides on immune function and brain health. Key Topics Discussed Understanding Aloe Polysaccharides What are Aloe polysaccharides? How are they extracted and formulated for nutritional supplements? Research on Alzheimer's Disease and Multiple Sclerosis Overview of Dr. Lewis's studies on Alzheimer's disease and MS. Impact of Aloe polysaccharides on cognitive function and disease progression. Immune System Modulation Effects of Aloe polysaccharides on CD4 to CD8 ratios. Regulation of key cytokines: TNF-alpha, VEGF, and BDNF. Balancing TH1 and TH2 responses. Brain Care Formulation Detailed discussion on the Brain Care formulation developed by Dr. Lewis. Clinical results and patient outcomes. Challenges in Nutritional Research Funding difficulties for nutritional and supplement research. Issues with the pharmacological model of placebo-controlled randomized double-blind trials. Why this model is challenging for evaluating supplements and nutritional interventions. Future Directions and Innovations Potential future applications of Aloe polysaccharides in other health conditions. Innovations in nutritional research methodologies. Key Takeaways Aloe Polysaccharides: Naturally occurring compounds with significant therapeutic potential, particularly in modulating immune function and supporting brain health. Clinical Research: Dr. Lewis's studies highlight the positive effects of Aloe polysaccharides on Alzheimer's disease, MS, and overall immune health. Nutritional Research Challenges: The current pharmacological model of clinical trials poses challenges for the study of supplements, necessitating new research approaches. Research References Studies on Alzheimer's disease and Aloe polysaccharides: Positive impacts on cognitive function and disease markers. Research on MS: Aloe polysaccharides and their role in managing symptoms and progression. Immune modulation: Detailed findings on CD4/CD8 ratios, cytokines (TNF-alpha, VEGF, BDNF), and TH1/TH2 balance. Dr. John Lewis provides compelling evidence on the health benefits of Aloe polysaccharides and underscores the need for innovative research methodologies in nutritional science. This episode offers valuable insights for anyone interested in the intersection of nutrition, immune function, and brain health.Connect with Dr. John Lewis Website: Dr. John Lewis Nutrition If you want to get Daily Brain Care visit our online curated range of cutting edge longevity and anti-aging supplements at  BIO John E. Lewis, Ph.D. is the Founder and President of Dr Lewis Nutrition™. Dr. John E. Lewis has spent most of his career developing a unique approach as someone who "walks the walk" through all of his combined professional and personal experiences to attaining optimal health through nutrition, dietary supplements, and exercise. Throughout his research career, he has evaluated many different nutritional approaches to enhancing well-being, particularly for brain health, immune function, and counteracting aging. He can separate fact from fiction regarding how to utilize nutrition and dietary supplements to help you achieve and maintain optimal health. If you need a trusted source of information, products, and services, then look no further than Dr. Lewis and how he can help you achieve your health-related goals. Professional Career Dr. Lewis is past full-time Associate Professor in the Department of Psychiatry and Behavioral Sciences at the University of Miami Miller School of Medicine and the Founder and President of Dr Lewis Nutrition™. He is a Diplomate, Faculty Member, and Advisor of the Medical Wellness Association. He has been the principal investigator of over 30 different studies on human health in his research career. During that time, he either directly raised or indirectly supported raising over $23 million in grants, gifts, and contracts for research studies and clinical trials and educational programs for medical students. In addition to his research, Dr. Lewis has been an invited national and international lecturer and guest speaker at conferences and as a guest on television shows. He is a well-known author with over 180 peer-reviewed publications in some of the world's leading scientific journals. He has also mentored many different students, from undergraduates to post-doctoral trainees, in not only how to conduct clinical research but to apply the principles of health promotion into daily practice. Research Interests Much of Dr. Lewis's research has focused on evaluating the effects of nutrition, dietary supplements, and exercise on various aspects of human health. He and his colleagues have been continually searching for ways to help people achieve and maintain health through natural treatments that align with our physiology. A primary stimulus for the origin of Dr Lewis Nutrition™ occurred after Dr. Lewis ran his landmark study on how an aloe polysaccharide multi-nutrient complex improved cognitive and immune functioning after 12 months in persons with moderate to severe Alzheimer's disease, leading to the creation of the dietary supplement, Daily Brain Care. Daily Brain Care showed clinically and statistically significant improvements in cognition according to the ADAS-cog cognition score and statistically significant improvements in inflammation (according to TNFα and VEGF), immune function (according to the CD4/CD8 ratio), and adult stem cells (according to CD14+ cells). His seminal publication from the study in the Journal of Alzheimer's Disease not only spurred him to leave academics and pursue a science-based business career, but also enabled him to be selected for a widely-acclaimed TEDxMiami talk. Founding Dr Lewis Nutrition™ While Dr. Lewis still maintains an academic affiliation, he chose to leave a full-time research career to pursue his true passion of helping people achieve health through nutrition, dietary supplements, and exercise. His research in brain health and immune function was key in the creation of Daily Brain Care, but afterward he chose to shift into business where the opportunity to reach a larger audience is greater. Dr Lewis Nutrition™ is the vehicle through which Dr. Lewis leverages his many years of personal and professional work to spread a message of health that is so desperately needed, particularly for those who are afflicted with an all-too-common chronic disease, e.g., neurodegeneration, immune dysfunction, or cardiac and metabolic disorder. Dr. Lewis will continue to be a thought leader to help people utilize the power of nutrition and dietary supplements and learn how to take control of and optimize their health.         Personalised Health Optimisation Consulting with Lisa Tamati Lisa offers solution focused coaching sessions to help you find the right answers to your challenges. Topics Lisa can help with:  Lisa is a Genetics Practitioner, Health Optimisation Coach, High Performance and Mindset Coach. She is a qualified Ph360 Epigenetics coach and a clinician with The DNA Company and has done years of research into brain rehabilitation, neurodegenerative diseases and biohacking. She has extensive knowledge on such therapies as hyperbaric oxygen,  intravenous vitamin C, sports performance, functional genomics, Thyroid, Hormones, Cancer and much more. She can assist with all functional medicine testing. Testing Options Comprehensive Thyroid testing DUTCH Hormone testing Adrenal Testing Organic Acid Testing Microbiome Testing Cell Blueprint Testing Epigenetics Testing DNA testing Basic Blood Test analysis Heavy Metals  Nutristat Omega 3 to 6 status and more  Lisa and her functional medicine colleagues in the practice can help you navigate the confusing world of health and medicine . She can also advise on the latest research and where to get help if mainstream medicine hasn't got the answers you are searching for whatever the  challenge you are facing from cancer to gut issues, from depression and anxiety, weight loss issues, from head injuries to burn out to hormone optimisation to the latest in longevity science. Book your consultation with Lisa    Join our Patron program and support the show Pushing the Limits' has been free to air for over 8 years. Providing leading edge information to anyone who needs it. But we need help on our mission.  Please join our patron community and get exclusive member benefits (more to roll out later this year) and support this educational platform for the price of a coffee or two You can join by going to  Lisa's Patron Community Or if you just want to support Lisa with a "coffee" go to  https://www.buymeacoffee.com/LisaT to donate $3   Lisa's Anti-Aging and Longevity Supplements  Lisa has spent years curating a very specialized range of exclusive longevity, health optimizing supplements from leading scientists, researchers and companies all around the world.  This is an unprecedented collection. The stuff Lisa wanted for her family but couldn't get in NZ that's what it's in her range. Lisa is constantly researching and interviewing the top scientists and researchers in the world to get you the best cutting edge supplements to optimize your life.   Subscribe to our popular Youtube channel  with over 600 videos, millions of views, a number of full length documentaries, and much more. You don't want to miss out on all the great content on our Lisa's youtube channel. Youtube   Order Lisa's Books Lisa has published 5 books: Running Hot, Running to Extremes, Relentless, What your oncologist isn't telling you and her latest "Thriving on the Edge"  Check them all out at  https://shop.lisatamati.com/collections/books   Perfect Amino Supplement by Dr David Minkoff Introducing PerfectAmino PerfectAmino is an amino acid supplement that is 99% utilized by the body to make protein. PerfectAmino is 3-6x the protein of other sources with almost no calories. 100% vegan and non-GMO. The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! No other form of protein comes close to PerfectAminos Listen to the episode with Dr Minkoff here:    Use code "tamati" at checkout to get a 10% discount on any of their devices.   Red Light Therapy: Lisa is a huge fan of Red Light Therapy and runs a Hyperbaric and Red Light Therapy clinic. If you are wanting to get the best products try Flexbeam: A wearable Red Light Device https://recharge.health/product/flexbeam-aff/?ref=A9svb6YLz79r38   Or Try Vielights' advanced Photobiomodulation Devices Vielight brain photobiomodulation devices combine electrical engineering and neuroscience. To find out more about photobiomodulation, current studies underway and already completed and for the devices mentioned in this video go to www.vielight.com and use code “tamati” to get 10% off     Enjoyed This Podcast? If you did, subscribe and share it with your friends! If you enjoyed tuning in, then leave us a review and share this with your family and friends. Have any questions? You can contact my team through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts.  To pushing the limits, Lisa and team

Visit learnAMAstyle.com to uplevel your writing and editing skills with free downloads on medical writing and editing. The FDA has approved vonoprazan (Voquenza) for treating non-erosive gastroesophageal reflux disease (GERD) in adults. Vonoprazan is an oral potassium-competitive acid blocker (PCAB) already approved for erosive esophagitis and Helicobacter pylori infection. PCABs are a new class of medicines that inhibit stomach acid secretion. Non-erosive GERD is the most common form of GERD, affecting around 45 million US adults, with about 15 million treated with prescription medication annually. Many patients remain dissatisfied with existing treatments, experiencing symptoms that affect their quality of life. The approval of vonoprazan was based on the Phalcon-Nerd-301 study, a Phase 3 trial showing it significantly reduced heartburn episodes and provided more heartburn-free days and nights compared to placebo. The trial included 772 adults with frequent heartburn, demonstrating vonoprazan's effectiveness over placebo. The FDA has granted fast track designation to ADI-270 for metastatic or advanced clear cell renal cell carcinoma (ccRCC) in patients who previously received an immune checkpoint inhibitor and a VEGF inhibitor. ADI-270 is a CD70-targeted gamma delta CAR T-cell therapy designed to enhance resilience to the tumor microenvironment. A phase 1/2 trial will evaluate ADI-270 in patients with confirmed ccRCC who have been previously treated. The primary endpoints are the incidence of dose-limiting toxicities and the proportion of treatment-emergent adverse effects. The FDA has granted Fast Track and Regenerative Medicine Advanced Therapeutic (RMAT) designations to Lomecel-B, an investigational MSC therapy for Alzheimer's disease (AD). Lomecel-B aims to address neurodegeneration in AD and showed positive results in the CLEAR MIND Phase 2a trial. Visit learnAMAstyle.com to uplevel your writing and editing skills with free downloads on medical writing and editing.

PayerTalkCE™ Presents: Major Advances in the Management of Retinopathy of Prematurity (ROP) Step into the realm of groundbreaking strides in the battle against retinopathy of prematurity (ROP) in this PayerTalkCE episode. Hosted by Dr. Jeff Dunn (Cooperative Benefits Group), this episode features an enlightening conversation with Dr. Edward Wood (Austin Retina Associates), an expert in pediatric retinal diseases. As they delve into the complexities of ROP—a condition that poses a significant threat to the vision of premature infants—the duo sheds light on the critical importance of timely and accurate screening, diagnosis, and intervention. With insightful discussions on the nuances of treatment options, including the pivotal role of anti-VEGF therapy and laser treatments, this episode is a must-listen for healthcare professionals striving to safeguard the vision of our youngest and most vulnerable patients. This activity is certified for CME/CNE/CPE credit. To participate and earn credit, visit us at https://www.managedcareeye.com/ropcepodcast/. Find all of our network podcasts on your favorite podcast platforms and be sure to subscribe and like us. Learn more at www.healthcarenowradio.com/listen/

Visit learnAMAstyle.com for free downloads in writing in medicine and the life sciences.    The FDA has approved blinatumomab (Blincyto) for treating adult and pediatric patients one month or older with CD19-positive Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) in the consolidation phase. This bispecific T-cell engager (BiTE®) therapy targets CD19 surface antigens on B cells, allowing T cells to recognize and eliminate malignant B cells. The approval was based on the Phase 3 E1910 trial showing improved overall survival with blinatumomab plus chemotherapy compared to chemotherapy alone.   The FDA has approved roflumilast cream 0.15% (Zorvye) for treating mild to moderate atopic dermatitis (AD) in patients aged 6 years and older. This steroid-free, once-daily topical treatment is a selective, highly potent phosphodiesterase 4 (PDE4) inhibitor designed for long-term disease control. The approval was based on phase 3 studies showing significant improvements in disease clearance, itch reduction, and overall skin condition compared to the vehicle group.   The FDA has approved a new 6mg single-dose prefilled syringe for faricimab-svoa (Vabysmo), facilitating easier administration for neovascular (wet) age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO). Faricimab-svoa is a VEGF and Ang-2 inhibitor, now available in a ready-to-use format. This approval provides an alternative to the existing single-dose vial and is granted to Genentech.   The FDA is set to decide on OX124, a high-dose naloxone nasal rescue medication designed to reverse opioid overdoses, with the PDUFA date set for July 15, 2024. Developed by Orexo, OX124 offers rapid absorption, high bioavailability, and enhanced stability, addressing the critical need for potent rescue medications due to the high rate of synthetic opioid overdoses. If approved, OX124's launch is anticipated later in 2024.   The FDA accepted an NDA for vonoprazan (Voquezna) tablets for treating heartburn associated with Non-Erosive gastroesophageal reflux disease (GERD) in adults, with the PDUFA date set for July 19, 2024. Vonoprazan is a potassium-competitive acid blocker (PCAB) offering an alternative to traditional proton pump inhibitors (PPIs). Non-Erosive GERD, affecting 38 million U.S. adults, is characterized by reflux-related symptoms without esophageal mucosal erosions, impacting quality of life with symptoms like heartburn and chest pain.  

One of the challenges associated with current anti-VEGF therapies for the management of DME is the need for frequent injections and the potential impact on adherence and vision outcomes. Join Dr. John Kitchens and Dr. Maria Berrocal as they share their experiences treating their DME patients using a therapy with a novel mechanism of action, and how those patient outcomes have influenced their extension decisions and treatment management approaches. This special episode of New Retina Radio, and its content, is supported by Genentech USA, Inc. 

Too busy to read the Lens? Listen to our weekly summary here! In this week's episode we discuss… There is a significant association between chronic kidney disease and late age-related macular degeneration. Patients with proliferative diabetic retinopathy treated with panretinal photocoagulation monotherapy had higher rates of vitrectomy, vitreous hemorrhage, and tractional retinal detachment compared to anti-VEGF monotherapy. The curved shape of scleral contact lenses significantly increases Acanthamoeba adhesion compared to flat lenses.

CardioNerds Co-Founder Dr. Daniel Ambinder, Episode Chair Dr. Dinu Balanescu, and FIT Lead Dr. Natalie Tapaskar discuss advanced heart failure in CardioOncology with expert Dr. Richard Cheng. Audio editing by CardioNerds Academy Intern, Dr. Akiva Rosenzveig. In this episode, we discuss the spectrum of advanced heart failure in patients with a history of cancer. We dissect cancer therapy-related cardiac dysfunction (CTRCD) cases and the imaging and biomarker tools available for risk stratification and disease monitoring. We delve into the data on the use of guideline-directed medical therapy (GDMT) and cardiac resynchronization therapy (CRT) in these patients. We discuss the risk of prior radiation and chemotherapy during cardiac surgery. Finally, we learn about the post-transplant risk of rejection, recurrent malignancy, and de-novo malignancies, as well as treatment strategies we can employ for these patients. This episode is supported by a grant from Pfizer Inc. This CardioNerds Cardio-Oncology series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Giselle Suero Abreu, Dr. Dinu Balanescu, and Dr. Teodora Donisan.  CardioNerds Cardio-Oncology PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes - Advanced Heart Failure in CardioOncology Use the HFA-ICOS risk tool to understand the baseline risk of developing cancer therapy-related cardiac dysfunction (CTRCD). Key factors are type of cancer therapy, baseline CV risk factors, and age. A relative change in global longitudinal strain of more than 15% from baseline is a marker of early cardiac dysfunction and predicts the subsequent risk for systolic dysfunction in patients undergoing cardiotoxic chemotherapy. Statins may be useful in prevention of cardiovascular dysfunction in patients receiving anthracycline chemotherapy. There is limited data on the 4 pillars of GDMT in prevention of CTRCD, but should be started early once CRTCD is suspected or diagnosed! Mediastinal radiation causes adhesions and scarring which increase the risk of bleeding during cardiac surgery, lead to longer operative times, and can lead to RV failure and poor wound healing. Patients with a pre-transplant history of malignancy have a higher risk of mortality due to post-transplant malignancy. And patients with active cancer should not be considered for heart transplant. Post-transplant malignancy risk can be mitigated by utilizing an mTOR based, CNI free immunosuppression regimen. Show notes - Advanced Heart Failure in CardioOncology How do cardio-oncology and advanced heart failure intersect? There are 3 basic populations of patients to consider:Patients with advanced heart failure who develop cancer.Patients with pre-existing chemotherapy and radiation exposure for cancer treatment who later develop advanced heart failureHeart transplant recipients who, in the long term are at very high risk of developing cancer Cardio-oncologists must consider risk assessment and mitigation, long-term prognosis, and treatment strategies for each of these unique populations. How can we assess the risk of developing cardiovascular disease during cancer treatment (CTRCD)? There are many proposed risk tools. However, the majority are not well-validated. One of the most used tools is the HFA-ICOS risk tool.1You can select the planned cancer therapy for the patient (anthracyclines, HER-2, VEGF, RAF/MEK inhibitors, Kinase inhibitors, multiple myeloma therapies) and then calculate their risk of developing CV disease during cancer treatment based on baseline variables:1) previous history of CV disease,2) biomarkers – troponin and NT-proBNP3)age,4) CV risk factors -HTN, DM,

This episode challenges common perceptions about exercise, delving deep into the benefits of vigorous exercise for not just physical health but also brain function, aging, and even cancer prevention. It tackles fundamental questions, like what genetic and metabolic adaptations occur with vigorous exercise and how it can contribute to combating heart's age-related changes. We also unpack how these rigorous exercises affect glucose transport, mitochondrial health, and brain health at an intricate level. Lastly, it introduces practical applications like the Norwegian 4x4 interval training protocol, the benefits of "exercise snacks," and how to incorporate vigorous-intensity exercise into everyday life. In this episode, I discuss: (00:00) Introduction (04:34) What differentiates "vigorous" from "zone 2" training (08:34) Ties between VO2 max & life expectancy (11:55) Why zone 2 training doesn't guarantee VO2 max improvements (14:17) How to balance zone 2 training & vigorous-intensity workouts (16:17) Why the Norwegian 4x4 protocol may improve your VO2 max (19:35) Evidence-based methods to estimate VO2 max outside a lab. (22:33) What it takes to reverse 20 years of heart aging: a two-year protocol (28:24) HIIT and type 2 diabetes – how vigorous exercise can reduce risk. (29:38) The mitochondria argument: HIIT vs. Zone 2 – which intensity is better? (32:09) Rethinking the 80-20 rule for everyday exercisers (less zone 2, more effort) (35:18) The role of high-intensity workouts in enhancing mitophagy (38:03) Why lactate accumulation from higher training intensity benefits the brain (40:28) Why the "glucose sparing" effect of lactate benefits brain injury and aging (43:26) The unique BDNF benefits of high-intensity exercise: the lactate advantage (44:42) The angiogenic effects of VEGF on the blood-brain barrier (in response to lactate) (46:58) The greater the exercise intensity, the greater the myokine release (49:48) How physical activity affects death risk in breast & colorectal cancer survivors (50:56) How vigorous aerobic exercise kills circulating tumor cells (52:36) Why exercise reduces depression and neurotoxicity (kynurenine mechanism) (54:13) The surprising power of "exercise snacks" against mortality (1:01:36) Download "The Cognitive Enhancement Blueprint" at https://bdnfprotocols.com/  Get the latest distilled information straight to your inbox several times per month: https://www.foundmyfitness.com/newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/premium Learn more about our premium podcast, The Aliquot: https://www.foundmyfitness.com/aliquot