Podcasts about Bevacizumab

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.

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.

BUFFALO, NY - February 18, 2025 – A new #researchpaper was #published in Oncotarget, Volume 16, on February 12, 2025, titled “Could Panitumumab with very low dose Capecitabine be an option as a maintenance regimen." In this study, researchers Doaa A. Gamal, Aiat Morsy, and Mervat Omar from Assiut University Hospital, evaluated a new maintenance treatment for metastatic colorectal cancer (mCRC). Their findings suggest that a combination of two drugs—Panitumumab, a targeted therapy that blocks a protein called epidermal growth factor receptor to slow cancer growth, and low-dose Capecitabine, a chemotherapy drug that converts into 5-fluorouracil (5-FU) inside the body to stop cancer cells from growing and dividing—could help extend survival in patients with mCRC. This regimen appears to be both effective and well-tolerated, especially for patients with wild-type KRAS mCRC who had previously responded to treatment. Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Standard treatment often involves a combination of chemotherapy and targeted therapies, but many patients face challenges related to treatment toxicity and resistance, which can lead to treatment interruptions. This study tested whether a lower-intensity maintenance treatment could help keep the cancer under control after initial treatment. The study involved 25 mCRC patients with wild-type KRAS and BRAF, who first received six rounds of standard 5-FU-based chemotherapy with Panitumumab. Patients who responded well then switched to a maintenance treatment of Panitumumab every two weeks and a low, continuous dose of Capecitabine. The results showed that patients had a median progression-free survival of 18 months and a median overall survival of 45 months, indicating a strong potential benefit. Patients with metastases detected at the same time as the primary tumor showed a longer progression-free survival than those with metastases appearing later. The treatment was also well tolerated, with only 8% of patients experiencing severe side effects such as skin rash or diarrhea, which were managed with standard treatments. "In our research, the toxicity profile was very acceptable, and no patients needed to stop treatment or had a dose modification due to toxicity." Finding a way to keep cancer under control while reducing side effects is a major goal in cancer treatment. While other maintenance therapies like Bevacizumab and Cetuximab have been studied, this research suggests that Panitumumab with low-dose Capecitabine could be a promising new option. Panitumumab is already an FDA-approved drug, but its role in maintenance therapy had not been extensively explored. The results of this study suggest that this combination may help delay disease progression while keeping side effects manageable, ultimately improving patients' quality of life. Although larger studies are needed, these findings open the door for further clinical trials to confirm the benefits of this regimen. If validated, this approach could change the standard of care for mCRC patients, particularly those who cannot tolerate more intensive chemotherapy. DOI - https://doi.org/10.18632/oncotarget.28687 Correspondence to - Doaa A. Gamal - doaaalygamaal@gmail.com Video short - https://www.youtube.com/watch?v=wuPSS0EdK-8 To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

In the past five years, the use of immunotherapeutic agents for advanced cancers has emerged as a promising alternative to tyrosine kinase inhibitors and chemotherapy, making it an exciting time to be practicing oncology. In this episode, Dr. Tyler Sandow interviews oncology experts about the landscape of advanced hepatocellular carcinoma (HCC) and the current state of immunotherapy treatments. He is joined by medical oncologists Dr. Jonathan Mizrah, Dr. Lingling Du, and Dr. Adam Burgoyne, as well as interventional oncologist Dr. Zachary Berman. Physicians, nurses, nurse practitioners, and physician assistants can follow this link to earn CME / CE credits for completing an accredited learning activity related to this discussion: https://www.cmeuniversity.com/course/take/125737 --- This podcast is supported by an educational grant from: AstraZeneca https://www.astrazeneca.com/our-therapy-areas/oncology.html With additional support from: Boston Scientific https://www.bostonscientific.com/en-US/medical-specialties/interventional-radiology/interventional-oncology.html --- SYNPOSIS Drs. Burgoyne and Mizrahi provide a primer on immunotherapy and explain how they communicate the principles of this treatment to their patients. Dr. Du discusses the Imbrave clinical trial and how recent studies have shown improved overall survival when immunotherapeutic agents are used, especially when multiple agents targeting various pathways are employed. When choosing between different regimens, the doctors consider factors such as the patient's underlying liver function, symptom burden, and prior treatments. Importantly, the doctors also discuss contraindications to immunotherapy, including a history of organ transplant, autoimmune disease, and poor performance status—all of which put patients at high risk for deterioration with this treatment. The treatment of patients with poor liver function remains controversial, as underlying cirrhosis may prevent the recovery of liver function. Dr. Berman outlines recent clinical trials studying the effects of transarterial chemoembolization (TACE) combined with immunotherapy. Finally, the doctors discuss the future of HCC treatment and the benefits of continued innovation in both interventional and medical oncology. --- TIMESTAMPS 00:00 - Introduction to Immunotherapy 04:32 - Notable Clinical Trials 13:39 - HCC Etiology and Immunotherapy Outcomes 18:43 - Contraindications for Immunotherapy 23:05 - Adverse Effects from Treatment 25:14 - Combination Therapy 36:22 - Considerations for Immunotherapy Dosing 40:26 - The Future of HCC Treatment --- RESOURCES Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma, IMbrave150 Trial (Finn et al, 2020): https://pubmed.ncbi.nlm.nih.gov/32402160/ Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma, HIMALAYA Trial (Abou-Alfa et al, 2022): https://evidence.nejm.org/doi/full/10.1056/EVIDoa2100070 Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial (Yau, 2022): https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00604-5/abstract Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line treatment for unresectable hepatocellular carcinoma (uHCC): First results from CheckMate 9DW (Galle, 2024): https://ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA4008 Randomized Phase 3 LEAP-012 Study: Transarterial Chemoembolization With or Without Lenvatinib Plus Pembrolizumab for Intermediate-Stage Hepatocellular Carcinoma Not Amenable to Curative Treatment (Llovet, 2022): https://pubmed.ncbi.nlm.nih.gov/35119481/ Find this episode on BackTable.com for more resources.

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!

Lisata Therapeutics Executive Vice President and Chief Medical Officer Dr. Kristen Buck joined Steve Darling from Proactive to announce a new research agreement with the University of Cincinnati to explore Lisata's novel cyclic peptide, certepetide, combined with bevacizumab, for treating endometriosis. Bevacizumab has shown effectiveness against endometriosis, yet its high dosages lead to systemic side effects, limiting its suitability for young, otherwise healthy women. Under this agreement, the University of Cincinnati will conduct the research while Lisata provides funding and supplies of certepetide. Lisata hopes this combination will offer a targeted, effective solution for endometriosis—a painful condition affecting 6.5 million U.S. women, often leading to severe pain, infertility, and other health complications. #proactiveinvestors #lisatatherapeuitcsinc #nasdaq #lsta #endometriosis #certepetide #Certepetide #EndometriosisTreatment #UniversityofCincinnati #WomensHealth #MedicalResearch #Biotechnology #Integrins #Neuropilin #ProactiveInterview #invest #investing #investment #investor #stockmarket #stocks #stock #stockmarketnews

In today's episode, supported by Taiho Pharmaceutical, we had the pleasure of speaking with Joleen Hubbard, MD, about practice-changing updates to the colorectal cancer (CRC) treatment paradigm. Dr Hubbard is a medical oncologist at Allina Health Cancer Institute in Minneapolis, Minnesota. In our exclusive interview, Dr Hubbard discussed key efficacy and safety findings from the phase 3 SUNLIGHT trial (NCT04737187) of trifluridine-tipiracil (Lonsurf) plus bevacizumab (Avastin) in patients with refractory metastatic CRC; quality of life outcomes from this trial; and the most practice-changing updates to the National Comprehensive Cancer Network guidelines for CRC.

Dr. Matt Feng is joined by Dr. Thomas H. Dohlman to discuss the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high-risk corneal transplantation, from his Ophthalmology Science article “Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation” Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation. Dohlman, Thomas H. et al. Ophthalmology Science, Volume 4, Issue 4.

Send us a Text Message.In this episode of the podcast, host Natalie Watson explores the comprehensive management of Recurrent Respiratory Papillomatosis (RRP), bringing together three top experts:  Dr Andile Sibiya from South Africa, Mr Adam Donne from the UK, and Prof Craig Derkay from the USA. The discussion covers various aspects of RRP, including differences in patient presentation and healthcare systems across the three countries, the impact of HPV vaccination, and evolving treatment modalities. Dr. Sibiya discusses the challenges in South Africa, highlighting delays in diagnosis and access to specialized ENT services, particularly for pediatric patients. She emphasizes the need for centralizing care for younger children and the limitations posed by a tiered healthcare system. Sibiya also mentions the significant disease burden and the approach of using surgery as a primary treatment, with consideration for adjuvant therapies, despite limited access to certain treatments like Bevacizumab.Adam Donne outlines the situation in the UK, where the National Health Service facilitates early referral for hoarseness, a red flag symptom. He notes the prevalence of RRP and the transition from primarily surgical treatments to incorporating adjuvant therapies such as the Quadrivalent vaccine, Cidofovir, and Bevacizumab. Donne underscores the importance of specialist centres and the evolving treatment landscape, reflecting a shift towards medical management.Craig Derkay provides insights from the US, describing the typical presentation of RRP in children and adults and the role of tertiary care centres in managing the disease. He highlights the promising results of intravenous Bevacizumab in reducing the need for repeated surgeries and the psychological burden on patients. Derkay also discusses the potential of new DNA vaccines in phase three trials, which show promise in significantly reducing or even curing RRP.The episode concludes with a consensus on the need for earlier adoption of adjuvant therapies to minimize long-term damage and improve patient outcomes, alongside excitement about future developments in vaccine research. The experts agree on the importance of a multidisciplinary approach, involving patients and families in treatment decisions and maintaining a focus on innovative solutions to improve the care and prognosis of RRP patients.Contact InformationVisit www.britishlaryngological.org or download BLA Connect from your app store for further information and details on becoming a BLA member.Register for Cutting Edge Laryngology 2024, 2-4 October 2024, at the Royal Society of Medicine London, here. Email: enquiries@britishlaryngological.org for any questions or topic suggestions you may have for future episodes. This show is brought to you by the BLA, you can follow us on Twitter, Facebook, Linkedin and Instagram hosted by Natalie Watson @surgeonsinger produced and directed by Heather Pownall of Heather's Media Hub Ltd. The opinions of our host and guests are their own; The BLA does not endorse any individual viewpoints, given products or companies. If you enjoyed this podcast, please rate, review and subscribe with the podcast provider of your choice.

Patients with DME in DRCR Retina Network Protocol AC were switched from bevacizumab to aflibercept if they met specific switch criteria. Where there any baseline factors that predicted a switch? Moderator Rebecca Soares, MD, sits down with panelists Matt Starr, MD, and Nikisha Kothari, MD, to review this study, ask whether the findings are clinically relevant, and explore other risk factors that may be worthy of further investigation. 

CME credits: 1.00 Valid until: 17-07-2025 Claim your CME credit at https://reachmd.com/programs/cme/pivotal-data-supporting-first-line-atezolizumabbevacizumab-in-unresectable-hcc/26331/ This online MinuteCE program provides a comprehensive evaluation of the latest clinical data on first-line immune checkpoint inhibitor (ICI) combinations for the treatment of unresectable hepatocellular carcinoma (HCC). Participants will critically assess survival outcomes and other key efficacy metrics from recent studies. The program emphasizes the application of efficacy and safety data to tailor treatment regimens based on individual patient profiles and preferences. Additionally, it addresses the recognition and management of treatment-related adverse events associated with these regimens. The course also incorporates strategies for effective communication and shared decision-making within the multidisciplinary care team, ensuring optimal patient-centered care.

Featuring perspectives from Ms Deanna A Griffie, Ms Caroline Kuhlman, Dr Manish A Shah and Dr John Strickler, including the following topics: Introduction (0:00) The Current Role of Anti-PD-1/PD-L1 Antibodies in the Management of Nonmetastatic Gastroesophageal Cancers (11:30) The Potential Role of Immune Checkpoint Inhibitors (ICIs) as Neoadjuvant Therapy for Patients with Gastric/Gastroesophageal Junction Cancer (20:53) First-Line Therapy for Metastatic Gastroesophageal Cancers (36:16) The Potential Role of Therapy Targeting Claudin 18.2 for Gastroesophageal Cancers (42:16) Targeted Therapies for HER2-Positive Gastroesophageal Cancers (51:42) Selection of Appropriate Candidates with Localized Colorectal Cancer (CRC) for Adjuvant Therapy (1:14:24) The Current Role of ICIs in the Treatment of Metastatic CRC (mCRC) (1:23:32) Tolerability and Other Practical Considerations with ICIs (1:25:57) The Role of TAS-102/Bevacizumab in the Management of Relapsed/Refractory (R/R) mCRC (1:36:14) The Potential Role of KRAS-Targeted Therapy in the Management of mCRC (1:44:36) NCPD information and select publications

Drs. David Eichenbaum and Priya Vakharia share their insights on biosimilars in the treatment of retinal disease in the United States.

In many parts of the world, Bevacizumab is an important component of the treatment of glioblastoma, colorectal, hepatocellular and ovarian cancers. However, with such widespread use inevitably comes toxicity. Side effects related to bevacizumab are not your garden-variety chemotherapy side effects, nor are they similar to toxicity from immunotherapy. Rather, they stand apart, unique amongst our systemic therapies.In their latest Onconack, Josh and Michael take a look at two of the most commonly described toxicities related to bevacizumab: hypertension and proteinuria. This is sure to be a valuable resource to any oncology trainee blessed (or cursed) with the unit pager!Links to useful sources for further reading (subscription may be required):Chemotherapy plus bevacizumab as an optimal first-line therapeutic treatment for patients with right-sided metastatic colon cancer: a meta-analysis of first-line clinical trials. https://doi.org/10.1136/esmoopen-2019-000605Practical Management of Bevacizumab-Related Toxicities in Glioblastoma. https://pubmed.ncbi.nlm.nih.gov/25568148/Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer. https://www.nejm.org/doi/10.1056/NEJMoa1104390?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.govBevacizumab Increases Risk for Severe Proteinuria in Cancer Patients. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938590/For more episodes, resources and blog posts, visit www.inquisitiveonc.comFind us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of Music Unlimited: https://pixabay.com/users/music_unlimited-27600023/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

In this JCO Article Insights episode, Rohit Singh provides summary on two articles published in the April 10th issue of the Journal of Clinical Oncology. The first article, "Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04)" describes a randomized, open-label, multicenter, phase III study evaluating the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK-mutated NSCLC that progressed before TKI therapy. The second is the accompanying Oncology Grand Rounds. TRANSCRIPT The guest on this podcast episode has no disclosures to declare. Dr. Rohit Singh: Hello and welcome to JCO Article Insights. I'm your host, Dr. Rohit Singh. Today I will provide a summary of a Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04), by Dr. Park and colleagues from Seoul, Korea. The purpose of this study was to evaluate the efficacy and safety of the ABCP regimen based on IMpower150 in patients with EGFR or ALK mutated non-small cell lung cancer who had progressed on prior targeted treatment.   I will also discuss an Oncology Grand Round case titled "Management of Treatment Resistance in Patients with Advanced EGFR Lung Cancer: Personalization, Parsimony, and Partnership", by Dr. Vallillo and colleagues from Lahey Hospital Medical Center and Tufts University School of Medicine, Boston, Massachusetts. Oncology Grand Round cases help us to give a clinical context to the clinical trial.   While TKIs are the established standard of care for non-small cell lung cancer harboring driver mutations, most patients will develop resistance to these treatments. Immune checkpoint inhibitors, with or without chemo, have shown clinical benefits of immune checkpoint monotherapy in patients with EGFR-mutated non-small cell lung cancer. Consequently, platinum-based chemo is the standard of care for patients with EGFR TKI failure. This was a phase III, multicenter, open-label, randomized trial conducted at 16 hospitals across the Republic of Korea. Patients diagnosed with stage four non-small cell lung cancer with sensitizing EGFR mutation or ALK translocation were included in the study. Patients were randomly assigned to the ABCP arm or chemo-only arm in a 2:1 ratio. Eligible patients were stratified on the mutation type (EGFR mutation vs. ALK translocation) and the presence of brain metastasis. No crossover to atezolizumab was permitted.  The recruitment with T790M mutation was capped at 30%. Patients who responded continued to receive maintenance with atezolizumab until disease progression or unacceptable toxicities occurred. If a patient was identified to have an acquired T790M mutation after the failure of a first or second-generation EGFR TKI, the patient had to be treated with a third-generation EGFR TKI before enrollment. The primary endpoint was investigator-assessed objective response rate according to research criteria. The secondary endpoints included overall survival and progression-free survival at one and two years, and the duration of response, along with a safety analysis. Investigators also did an exploratory biomarker analysis based on PD-L1 expression and its correlation with the response. They also analyzed the distribution of tumor-infiltrating lymphocytes, and a cut-off of 20% inflamed score was used to compare the two arms. Overall, 228 patients were enrolled, 154 in the ABCP arm and 74 in the chemo-only arm. Most patients were female at 56.1% and never smokers at 62.7%. Brain metastasis was present in 42.7% of patients. Most patients had previously received EGFR TKI therapy, however, only 8% and 30% received third-generation TKI as first-line therapy in the ABCP arm and  chemo-only arm, respectively. The majority of the patients were EGFR at  90%.  The median duration of follow-up for the study population was 26 months. The objective response rate in the ABCP arm was significantly higher at 69.5% compared to 42% in the chemotherapy alone arm. The median PFS was significantly longer in the ABCP arm at 8.48 months versus 5.6 months, and the duration of response was similar at around seven months in both arms. The median overall survival was also similar at around 20 months in both arms, with a hazard ratio of 1.01. In the subgroup of patients with brain metastasis at the time of study enrollment, PFS was significantly longer in the ABCP arm at 8.4 months compared to 4.4 months in the chemotherapy-only arm. In contrast, no difference in PFS was observed in the subgroup without brain metastasis. Regarding EGFR mutation status, there was no difference in PFS or OS between the two arms in the EGFR deletion 19 subgroup. However, a favorable PFS was observed in the EGFR L858R subgroup. For those with acquired EGFR T790M mutation, there was no difference in PFS between groups, whereas a favorable PFS was observed in the subgroup without EGFR T790M mutation.  In the exploratory biomarker analysis, interestingly, the impact on PFS was correlated with PD-L1 expression. The study found that the higher the PD-L1 expression, the better the PFS. In patients with PD-L1 expression of more than 50%, the hazard ratio was 0.24 for PFS. This is an interesting observation. As in previous studies, we have seen that PD-L1 expression does not have a strong association with response to checkpoint inhibitors in patients with driver mutations. Based on the distribution density of tails in the tumor bed, the inflamed score was calculated using artificial intelligence. For patients with 20% of the imflamed score, the ABCP arm has significantly prolonged PFS at 12.9 months compared to 4.8 months. The median number of ABCP treatment cycles was 4, with 12 for atezolizumab and 8 for bevacizumab as maintenance therapy, pemetrexed maintenance was administered for a median of 10 cycles. The incidence of grade 3 or higher side effects was 35.1% in the ABCP arm compared to 15% in the chemotherapy-only arm. Peripheral neuropathy, alopecia, and myalgias were the most prevalent side effects. Interesting notably, 54% of patients in the ABCP arm required treatment interruption or dose modification, and there were three reported deaths in the ABCP arm, two due to pneumonia and one due to cerebral embolic infarction. Around 10 patients or 13.5% of patients in the chemotherapy-only arm required dose interruption or modification.   In conclusion, patients with EGFR-mutated or translocated non-small cell lung cancer who had failed prior TKI ABCP regimen showed a statistically significant prolongation of PFS and response rate compared to chemo alone. Patients in the subgroup with EGFR L858R, without acquired T790M mutation, and presence of brain met showed more benefit. There was no difference in overall survival, though we need more mature data. Adverse events were higher in the ABCP arm. Interestingly, in the exploratory analysis, a high PD-L1 and an inflamed score of more than 20% showed PFS benefits. Though we need to take into consideration that this trial was done and all the patients were grouped from a single country considering Asian ethnicity. And most importantly, the majority of patients were treated with first- and second-generation TKIs, whereas third-generation TKIs are the standard of care in the United States.  Coming to the Oncology Grand Round, in this case, we will discuss the management of treatment resistance in patients with advanced EGFR-mutated lung cancer. A patient with a 20-pack-a-year history of tobacco use presents with weight loss and hip pain, found to have a lung mass, skeletal mets, and brain mets, and was diagnosed with lung adenocarcinoma. The patient goes with palliative radiotherapy for the brain mets. Comprehensive tumor Merkel profiling demonstrated an EGFR mutation exon 19 and alteration P53. The patient was started on third-generation EGFR TKI osimertinib. However, after 17 months, the patient has symptomatic disease progression. Usual approach, if feasible, re-biopsy at the time of progression to evaluate for possible new mutations which can guide treatment options. As mentioned earlier, in the trial, acquired resistance to the TKI is inevitable and heterogeneous. There were various mechanisms which have been proposed regarding resistance, including a second-site EGFR alteration, upregulation of bypass pathway, histological transformation to small cell histology, or suboptimal drug penetration.  There are various approaches after disease progression on EGFR TKI. Combining EGFR-directed therapies to address resistance is an option. Prime results from the MARIPOSA-2 study showed amivantamab plus chemotherapy with or without lazertinib in EGFR-mutated non-small cell lung cancer after disease progression showed a better objective response rate at 64% compared to 36% in the chemo-alone arm. It also showed improved PFS with a median of 6.3 compared to 4.2 in the chemo-alone arm. Combining immune checkpoint inhibitors, EGFR-mutated non-small cell lung, I say has been disappointing in advance of EGFR-mutated non-small cell lung, and combination therapy studies are needed to improve outcomes. Studies, as I discussed ATTLAS, have shown that combining a VEGF inhibitor with ICIs and chemotherapy can lead to a better objective response rate and PFS. However, further clinical trials are needed to figure out the better subgroup of patients who can benefit from this combination.   Should the TKI be continued beyond progression in EGFR-mutated advanced non-small cell lung cancer? Continuing the primary EGFR TKI treatment beyond progression may be considered for patients with indolent or asymptomatic progression or localized progression. We can consider radiation, surgery, or ablation. This approach will potentially delay the need to change systemic therapy in patients. However, for patients with multifocal disease progression requiring chain systemic therapy it may be more beneficial to switch to next-line systemic therapy options like platinum doublet with or without immunotherapy and VEGF inhibitors. In the case presented, the decision was made to continue osimertinib along with platinum doublet, deferring the addition of immunotherapy and VEGF inhibitor. This choice was based on factors like the patient's history of brain metastases and intracranial control. There is also a high risk of toxicity, especially pneumonitis, with immune checkpoint inhibitors after using targeted therapy, the patient showed clinical and radiographic improvement while on this treatment regimen.  The decision to continue or change therapy at cancer progression is based on factors like drug tolerability, patient preferences, and specific subgroups with different outcomes, such as those with brain metastasis or specific EGFR mutation subtypes. Choosing between combination therapy strategies that concept progression involves personalized decision-making to optimize treatment outcomes. Ultimately, the approach to management should be tailored to individual patient needs, preferences, and eligibility for different treatment modalities.  This is Rohit Singh. Thank you for listening to JCO Article Insights. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You will find all the ASCO shows at asco.org/podcasts. Thank you. 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 ofASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.        

Join the Oncology Brothers, Drs. Rahul and Rohit Gosain, in this engaging podcast episode as they delve into the treatment landscape for hepatocellular carcinoma (HCC) with Dr. Tanios S. Bekaii-saab from Mayo Clinic. The discussion covers the treatment options for different stages of HCC, including liver transplant, local therapy, and systemic treatments. Dr. Tanios S. Bekaii-saab provides insights on utilizing Atezolizumab with Bevacizumab, dual checkpoint inhibitors, and TKIs in advanced or metastatic HCC. Clinical pearls on managing side effects and patient selection criteria are also discussed. Don't miss this comprehensive overview of HCC treatment strategies in both community and academic settings. Stay informed and educated on the latest developments in oncology with the Oncology Brothers podcast series. Subscribe now for more insightful discussions on various cancer types and treatment approaches. #Oncology #HepatocellularCarcinoma #CancerTreatment #PodcastEpisode

Strickler, Leung, Dasari, and O'Neill discuss adverse effect monitoring and management with standard agents for patients with colorectal cancer.

Join experts Drs Kevin Kalinsky and Priyanka Sharma as they discuss their current approach to neoadjuvant therapy in triple negative breast cancer and how the SCARLET trial might change that. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/991256). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources Pembrolizumab for Early Triple-Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/32101663/ Clinical and Biomarker Results of Neoadjuvant Phase II Study of Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer (TNBC) (NeoPACT) https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.513 CALGB 40603 (Alliance): Long-Term Outcomes and Genomic Correlates of Response and Survival After Neoadjuvant Chemotherapy With or Without Carboplatin and Bevacizumab in Triple-Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/35044810/ NCCN Guidelines® Insights: Breast Cancer, Version 4.2023 https://pubmed.ncbi.nlm.nih.gov/37308117/ Pembrolizumab vs. Observation in People With Triple-negative Breast Cancer Who Had a Pathologic Complete Response After Chemotherapy Plus Pembrolizumab https://classic.clinicaltrials.gov/ct2/show/NCT05812807 Shorter Chemo-Immunotherapy Without Anthracycline Drugs for Early-Stage Triple Negative Breast Cancer https://clinicaltrials.gov/study/NCT05929768 Neoadjuvant Atezolizumab in Combination With Sequential Nab-Paclitaxel and Anthracycline-Based Chemotherapy Versus Placebo and Chemotherapy in Patients With Early-Stage Triple-Negative Breast Cancer (IMpassion031): A Randomised, Double-Blind, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/32966830/ Adjuvant Capecitabine for Breast Cancer After Preoperative Chemotherapy https://pubmed.ncbi.nlm.nih.gov/28564564/ Impact of Neoadjuvant Chemotherapy on Axillary Nodal Involvement in Patients With Clinically Node Negative Triple Negative Breast Cancer https://pubmed.ncbi.nlm.nih.gov/25266871/ Neoadjuvant Chemotherapy With or Without Anthracyclines in the Presence of Dual HER2 Blockade for HER2-Positive Breast Cancer (TRAIN-2): A Multicentre, Open-Label, Randomised, Phase 3 Trial https://pubmed.ncbi.nlm.nih.gov/30413379/

Listen to this live podcast from the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting with Oncology Data Advisor and Michael Halpern, MD!

Editor's Summary by Kirsten Bibbins-Domingo, PhD, MD, MAS, Editor in Chief of JAMA, the Journal of the American Medical Association, for the April 18, 2023, issue. Related Content: Audio Highlights

In this episode of the IJGC podcast, Editor-in-Chief, Dr. Pedro Ramirez, is joined by Laura Chambers to discuss the low-risk population in advanced ovarian cancer. Laura Chambers, DO is an Assistant Professor in the Division of Gynecologic Oncology at The James Cancer Center at The Ohio State University. Highlights: - Discuss historical perspectives of low and high-risk ovarian cancer, and how this has been analyzed in contemporary trials - Review of contemporary trials for PARPi and Bevacizumab maintenance in women with advanced ovarian cancer - Data obtained through un-powered sub-analysis from randomized clinical trials is hypothesis generating and care must be exercised in applying this to patient cohorts

Dr. Mohamed Salem, Dr. Myriam Chalabi, and Dr. Andrea Cercek discuss pivotal neoadjuvant immunotherapy clinical trials for patients with MSI-H/dMMR colorectal cancer, focusing on the development of active therapies in the neoadjuvant setting—where patients are treated without surgery, radiation, or chemotherapy—and the importance of patient selection in finding the right target and treatment to improve outcomes. TRANSCRIPT Dr. Mohamed Salem: Hello, and welcome to the ASCO Daily News Podcast. I'm your guest host today, Dr. Mohamed Salem. I'm a GI oncologist at the Levine Cancer Institute at Atrium Health. Today, we will be discussing very promising advancements in the neoadjuvant immunotherapy for patients with MSI-H/dMMR colorectal cancer. And I'm very delighted to welcome two world-renowned oncologists whose research has tremendously helped shape the treatment landscape of colorectal cancer. Dr. Myriam Chalabi is a GI medical oncologist at the Netherlands Cancer Institute, and Dr. Andrea Cercek is a medical oncologist at Memorial Sloan Kettering in the United States.  Our full disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available on our transcripts at asco.org/DNpod.  Dr. Chalabi and Dr. Cercek, welcome to the ASCO Daily News Podcast. Dr. Myriam Chalabi: Thank you for having me. Dr. Andrea Cercek: Thank you very much for having me. Dr. Mohamed Salem: It's a pleasure to have two world-renowned stars like you. Thank you for taking the time.  So, before we start going deep into the topic, obviously, now we are seeing emerging data in CRC using immunotherapy as the neoadjuvant approach, which actually can reduce or even eliminate some of the other treatment modalities and potentially save patients from toxicities. Both of you led what I think are landmark studies in this field. I wanted to give you the chance to tell our audience about your studies and why you think they're important. Dr. Cercek? Dr. Andrea Cercek: Sure. Thank you so much. So, our study was a neoadjuvant study in early-stage, locally advanced rectal cancer with tumors that were mismatch repair-deficient or MSI-H. And rectal cancer normally is treated with chemotherapy, chemoradiation, and surgery. And the goal of the trial was to utilize PD-1 blockade alone in this subpopulation and evaluate the response.  Patients received six months of dostarlimab, which is a PD-1 blocking agent, and then were evaluated for response. If there was no residual disease, they were able to avoid radiation and surgery. And what we've seen thus far in the presentation at GI ASCO in 2022 was that all patients who received six months of dostarlimab had a clinical complete response, so no residual tumor, and were able to avoid chemotherapy, radiation, and surgery and are on observation. And the study is ongoing and actively accruing patients. Dr. Mohamed Salem: All of us were very excited seeing that presentation at ASCO. And when we came back to the clinic everyone was talking about it, including patients, obviously. Thank you for this, Dr. Cercek. Dr. Chalabi, you also led a similar study that was actually presented in ESMO in 2022. Can you please give us, like, a brief description of that trial? Dr. Myriam Chalabi: Yeah, sure. So, this is the NICHE trial, and actually the NICHE trial has been ongoing for quite some time now. We recently presented a larger NICHE-2 study, but basically– so what we started out by doing in NICHE is giving patients what we considered back then a window of opportunity study. We treated patients with MMR-deficient tumors, which I'll be focusing on for now, with two cycles of nivolumab and one single cycle of low-dose ipilimumab. And patients all undergo surgery within six weeks of registration within the study. And back in 2020, we published the first data of NICHE-1 showing 100% pathologic responses with 60% pathologic complete responses and decided that this should definitely be a treatment that we need to explore in a larger group of patients. And that's where NICHE-2 was born, which we presented at ESMO last year, where we treated over 100 patients with this neoadjuvant approach of two cycles nivolumab, one single cycle ipilimumab, showing 99% pathologic responses, including 95% major pathologic responses and 67% pathologic complete responses. And this was all within five and a half weeks of the first treatment with immunotherapy, so a very short treatment duration with dual checkpoint blockade. Dr. Mohamed Salem: Amazing results, too. And I know you had a standing ovation when you presented the outcome of the study. And again, congratulations to you, your investigator, and also all the patients participated. Dr. Myriam Chalabi: Thank you so much.  Dr. Mohamed Salem: I guess the first question that comes to my mind - we have two trials, obviously, now we're moving from one size fits all to precision therapy, like getting actually the right treatment for the right patient. But in the NICHE study, it was a checkpoint inhibitor, and the rectal study was a single agent. I want to start with you, Dr. Chalabi. In your opinion, when should we use single agent or double blockade immunotherapy? Dr. Myriam Chalabi: That is a great question. I'm going to start off by saying that I don't know the exact answer. I don't think we know that answer. And Dr. Cercek is going to share also her thoughts on this because we're seeing, of course, fantastic responses with monotherapy as well in Dr. Cercek's study. And we've also seen that in a study by Dr. Overman with monotherapy. So that may suffice in some patients, although what we're seeing is that you need to treat patients longer, probably to achieve that response, at least clinically. And I think that is the difference with dual checkpoint blockade, that we're giving in NICHE where we're seeing these very deep responses in just under six weeks' time.  So, I think it may be more of a question of how long we want to treat patients for to achieve the endpoint that we're aiming for. And, of course, there may be, at some point, patients that need dual checkpoint blockade, but so far, we're seeing great responses in both of our studies. So I think we need more patients, more data to see whether we're going to see non-responders. And hopefully, the studies that are ongoing in the metastatic disease setting will give us at least a little bit of insight into what the differences are in response to mono and dual checkpoint blockade and whether we can tell which patients might benefit more from the combination. But I think there's still a lot of work to be done in that field. Dr. Mohamed Salem: I totally agree. Dr. Cercek, same question to you. What do you think?  Dr. Andrea Cercek: Dr. Chalabi answered beautifully and very comprehensively. I agree completely with what she said. It's hard to argue with the responses that we're seeing with PD-1 blockade alone. But then again, dual checkpoint inhibitors in the NICHE study with just one month of therapy had phenomenal responses as well. So I think it's a question of duration of therapy and, really importantly, what we're trying to achieve. If our goal is organ preservation, then perhaps longer duration is better. The question then becomes, can we do, should we do longer duration with dual checkpoint inhibitors versus single agent? So I think, as she concluded, I couldn't agree more that we just need more information, we need more work to do, basically to answer this question for our patients. Dr. Mohamed Salem: More to come and more studies, which is fascinating.  So, Dr. Chalabi, you created actually a new term on Twitter called ‘Chalabi Plot'. It was amazing to see such a response. But we're curious, among those patients who achieved complete response so far, did you see any relapse? Dr. Myriam Chalabi: Short answer, no.  we're waiting, of course on the disease-free survival data, the three-year DFS data for NICHE-2, and we hope to have that by the end of this year, beginning of next year. But as of now, we showed that data, and so far, we haven't seen any recurrences in, actually, any of the patients treated in NICHE-2. Dr. Mohamed Salem: Fantastic. Dr. Cercek. So I think your slide -- I remember clearly from the ASCO presentation -- was all complete response, every single patient.  Same question, did you see any relapse so far? Dr. Andrea Cercek: So far, no, we have not. Dr. Mohamed Salem: Amazing. So, Dr. Cercek, as you know, and obviously, this is metastatic disease, but in KEYNOTE-177, as you know, about 30% of patients with MSI-high tumors did not respond to checkpoint inhibitors. So that makes some of us feel nervous about using checkpoint inhibitors alone in colorectal cancer, even with MSI-high status. I was curious if you can comment on this and if there is a way we can perhaps sort out who actually is likely to respond and who is likely not going to respond. Dr. Andrea Cercek: I think that's a really important question and an excellent point. And we believe that the difference lies in the fact that in KEYNOTE-177, the patients had metastatic disease, whereas in our neoadjuvant studies that we're discussing, they have early-stage disease. And whether that has to do with the tumor differences, young tumors versus older tumors once they become metastatic, or the microenvironment, remains to be determined. But certainly, there is this pattern of incredible responses with checkpoint inhibitors in early-stage dMMR tumors. And in KEYNOTE-177, as you mentioned, about 30% of patients progressed. And I think we don't know why that is. We are seeing this, about a third of progressors repeatedly in the metastatic setting with checkpoint inhibitors. And so perhaps there is a population. But whether this is driven by genomics or something else, we don't know. Dr. Mohamed Salem: Great. So, along the same lines, especially rectal cancer, obviously, because surgical resection is a key component in the treatment paradigm, do you feel patients who achieve pathological complete response should still go under surgical resection or should go under the ‘watch and wait' approach? Dr. Andrea Cercek: In general, I'm a fan of organ preservation. I think in rectal cancer, the reasons are obvious. It's a challenging surgery. It's very toxic to the patients. It changes their lives forever. In survivorship, 30% of them require a permanent colostomy because of the location of the tumor. So there, the field of rectal cancer, in general, is moving towards non-operative management, even in the MSI-proficient patients, by trying to optimize therapy to increase clinical complete responses and therefore omit surgery. So that's the difference with rectal cancer. In colon cancer, it's a different discussion. I think for many patients, surgery is very straightforward. It's a hemicolectomy. It doesn't alter lifestyle in survivorship, so it's not as morbid as it is in rectal cancer. Of course, I think if a patient is older with MSI-deficient tumor perhaps can undergo surgery, then clinical complete responses become critical because then we can monitor them after just checkpoint blockade, and they don't need surgery.  The challenge there, and I would love to hear Dr. Chalabi's comments on this, too, is just that imaging is challenging. We have a hard time in colon cancer determining whether someone has a clinical complete response or not. It seems to be very different than in rectal cancer, where with endoscopy and with the rectal MRI, we really can't tell whether the tumor is still present or not. This remains a challenge in colon cancer. Dr. Mohamed Salem: Dr. Chalabi, I would like to hear your thoughts and also how you practice in Europe. I don't know if it's the same like here in US or different. Dr. Myriam Chalabi: I completely agree with Dr. Cercek. Well, if we look at the rectal cancer patients, I think this is fantastic. That even though this is a small population achieving this high clinical complete response rate, not having to operate or even give any chemotherapy or radiation therapy to these patients, it is extremely important both in the short term but also in terms of long-term complications and morbidity. When it comes to the colon cancer responses that we're seeing in NICHE, those are all pathologic responses, of course. And we have been evaluating also preoperatively using scans to see whether we can assess these complete responses based on imaging. That doesn't seem to be the case. We do see responses in all patients, so we see these are all very large bulky tumors that we're treating in NICHE-2. And we do see responses in almost all of these patients, but it's not close to complete responses, definitely not in all of the complete responders that we're seeing. So that makes it difficult.  And the question is, what if we would be waiting or treating longer because these bulky tumors need more time to disappear or to be cleared before you're going to see it on the imaging? So that is a question that I don't have an answer to just yet. We may be getting some more data on that with the currently ongoing trials. And as Dr. Cercek pointed out, the endoscopies when you have a right-sided colon tumor are different than doing just a sigmoidoscopy for a rectal tumor. So, we actually do have one patient who hasn't undergone surgery, and that is actually a patient with an MMR-proficient tumor within the NICHE trial who had a complete response. And that patient has a sigmoidal tumor, and he actually had toxicities which prevented him from undergoing timely surgery and now has a complete response after two years, both endoscopically and on imaging. So, he hasn't undergone surgery, and that is a great example of how we may be doing this in the future. It's an interesting case within the trial to follow and see how we can do it in the future. Dr. Mohamed Salem: That's fascinating news. So, was it MMR-proficient? Dr. Myriam Chalabi: Yes, this is an MMR-proficient tumor.  Dr. Mohamed Salem Wow. Any particular biomarkers that you think he or she had to predict that? Dr. Myriam Chalabi: We have treated more patients with MMR-proficient tumors. We have 31 patients, and we have seen actually responses in 9 out of 31 patients in the MMR-proficient tumors with the same combination of two doses of nivolumab and one of ipilimumab. We previously published on half of the cohort approximately on what the possible predictive biomarkers of response could be, and that was a costimulation for CD8 and PD-1. So PD-1 positive CD8 T cells. And we're currently doing the same work for the rest of the cohort. So hopefully, we'll be able to show that soon and see whether this still stands for the completed MMR-proficient cohort. But definitely also very exciting data for the MMR-proficient. Dr. Mohamed Salem: So, this is actually a very good segue to my next question because I know all of us are looking for this. Like, obviously, we're seeing a fascinating response in those patients with MSI-high tumors, but majority of colorectal cancer, as you know, they actually have MSS-proficient tumors. Any thoughts about how we can overcome the primary resistance for this tumor to checkpoint inhibitors? So let me start with you, Dr. Cercek.  Dr. Andrea Cercek: I'm very much looking forward to Dr. Chalabi's data on this because, honestly, we have not seen such amazing responses to immunotherapy in MSS tumors. The initial studies were complete flatline, no responses at all. And here, she just described a patient that had a complete response to just a month of checkpoint inhibitors. So that's phenomenal, and hopefully, we'll learn from the responders.  We believe that there is a subpopulation of MSS colorectal cancer that is more immune sensitive, immune hot, whichever term you like to use. And it's just a matter of appropriately identifying those patients. And personally, I think the answer lies in the neoadjuvant setting in early tumors where they're treatment-naive, not exposed to chemo, not exposed to radiation, younger, have their innate microenvironment. And so, I think it's likely a combination of the above. But obviously, the ultimate goal is to find out who those patients are and then potentially treat them just like this with immunotherapy. And that would be another nice chunk of the pie where we could utilize immunotherapy for our patients. Dr. Mohamed Salem: Very true. Dr. Chalabi, especially with your experience and just showing there is a chance for those people to respond, what are your thoughts about how we can overcome this primary resistance? Dr. Myriam Chalabi: It's great to be here with Dr. Cercek because, obviously, we have very similar interests but it's also good to see that we think the same way because I completely agree with what she just said in terms of neoadjuvant. I think that was one of the most important things that we did here, giving this neoadjuvant treatment in non-metastatic tumors. It's probably a very important driver in the responses that we're seeing. So, we've been seeing data now a bit more in the metastatic disease setting where MSS tumors seem to be responding to new generations of checkpoint blockade. And the question is how those would do in the neoadjuvant setting that would be even different than what we're seeing now. But there's definitely some proof of MSS tumors that can respond to immunotherapy. The question on how to overcome the primary resistance, I think that question is for us: Who are the patients with primary resistant tumors and why are they primarily resistant? And then we can think about how to change that and how to change them into the tumors that are responding. I think these types of data will be key to understand more and know; hopefully, even you said, in the metastatic disease setting, to make these tumors more pliable in response to immunotherapy. Dr. Mohamed Salem: I agree. So, both of you are leading us toward how to choose the right patient with the right target for the right treatment. That's an amazing journey you're taking all of us on.  So, Dr. Cercek, I have to admit that with your data, it created some problems for us in the clinic because all patients the following day came in asking for immunotherapy. We had a hard time trying to explain that maybe this is not the right treatment for them or, like, not the right platform. But I wanted to ask you, if we'll have a patient tomorrow in the clinic with localized rectal cancer and happen to have an MSI-high tumor, what would be your recommendation in terms of how to approach that patient? Dr. Andrea Cercek: I think, ideally, you would discuss clinical trials with the patient. We have opened the study now to not just rectal cancer but colon cancer and, in fact, all solid tumors that are mismatch repair-deficient. So I think at this time, the patients really should be treated on a clinical trial. As we learn more, in particular, until we are more comfortable assessing for a clinical complete response and follow-up. I think the surveillance piece will be critically important. In rectal cancer, it's well established, but it's not in the other tumor types. So my recommendation would be to enroll the patient on a trial. Dr. Mohamed Salem: Just to add to that too, obviously, as you know, there is now the cooperative group trial that's looking at that option and we obviously encourage all centers to participate and open that study to have this option for our patients. Dr. Chalabi, so what do you guys do in Europe for these patients? Dr. Myriam Chalabi: In Europe, it's a very different situation. I would have answered this question differently by saying, well, we don't have that option of treating patients outside of clinical trials. So basically, we have to make sure that we have clinical trials for these patients. And that's something that we've had for colon cancer patients. That is still the case. And we're getting rectal cancer trials also for patients with MMR deficient tumors and have those also for MMR proficient tumors. For us and I agree completely that we should be treating patients within clinical trials, we don't have another option. But still, even if we did, I think it's important to create data within clinical trials to be able to ultimately also show why this should be standard of care and how we can make it standard of care. Because if you're not accumulating that data, then it's going to become very difficult if accrual is lacking. Now, we treat patients either with standard-of-care treatments, but usually, we try to find something within clinical trials.  Dr. Mohamed Salem: I totally agree. And as we always say, the standard of care should be a clinical trial participation. So, I must say, both of you, Dr. Cercek and Dr. Chalabi, you made 2022 a very exciting year for us in GI cancers. You really changed the way we look at how to treat these patients and give them a huge chance of, I would say, actually cure and obviously organ preservation. So, I'm very curious to know what you are both are working on now and what we should expect in 2023 and 2024.  Dr. Andrea Cercek: So, for me, the study is ongoing, as I mentioned, and we've expanded to all mismatch repair-deficient solid tumors with the same approach of six months of dostarlimab and then the option of nonoperative management. And I think that it'll be important for us to learn in terms of responses on the luminal versus some of the other tumor types, like, for example, pancreas cancer, where we don't see these robust responses in the metastatic setting, that will be important to do. We're doing some correlative analysis, as Dr. Chalabi described as well in our patients.  And then, I'm interested in optimizing neoadjuvant approaches to minimize therapy in rectal cancer specifically. So, we have a study now for HER-2 amplified RAS wild-type patients with locally advanced rectal cancer with a similar approach of utilizing HER-2 targeted therapy first and then in combination with chemotherapy. In our case, it's a combination of trastuzumab and tucatinib and then chemotherapy with CAPOX and assessing for response and potential omission of radiation and surgery depending on responders. So, I'm very excited that study is open and actively accruing, and hopefully, we can get similar responses that we did in the MSI population with PD-1 blockade. Dr. Mohamed Salem: Is that only available at MSK? Dr. Andrea Cercek: It is at this time. However, we will likely be expanding, so if there's any interest, let me know. Dr. Mohamed Salem: Great. I'm sure many centers will be. Great. What about you, Dr. Chalabi? Any sneak peek in the future? Dr. Myriam Chalabi: So many sneak peeks, where to begin? I think it's very exciting to be working in this space at this time, and we're very lucky to be in it. So, for NICHE, we're actually accruing now in new cohorts for both MMR-deficient and MMR-proficient tumors. For the patients with MMR-deficient tumors, we're actually testing a new combination of nivolumab plus relatlimab, so anti-LAG-3 plus anti-PD1. And we're testing the same co-formulation in patients with pMMR tumors. In addition to another cohort for the pMMR tumors with nivolumab, all within this window of opportunity, as we did previously in NICHE, and to see if we're going to see more responses if these are going to be different tumors than the ones responding to nivolumab and ipilimumab. And for the MMR deficient tumors, we're treating longer with this combination now. So, we're operating after eight weeks instead of six weeks. We're giving two cycles, four weekly cycles, to see whether we can even improve the PCR rates, even though this is, of course, a different combination treatment. So, very exciting times for NICHE, and we'll have the readout for the DFS at the end of this year, so that's also very exciting. And then, well, it's similar to Dr. Cercek. So again, we're on the same page when it comes to these neoadjuvant treatments. We have actually an ongoing trial for neoadjuvant treatment of patients with MMR proficient rectal cancers, and that is using a combination of radiation therapy followed by a combination of atezolizumab or anti-PDL1 with Bevacizumab with the aim of organ sparing approach in these patients. And we actually presented stage 1 of this trial as a poster at ASCO GI, showing that we achieved 56% complete or near complete responses clinically at 12 weeks. And after at least a year of follow-up for all patients, we have 50% organ preservation. So those are very exciting data as well. Also, in the MMR proficient tumors, I'm very excited to hear about the HER-2-positive tumors and Dr. Cercek's study. So there's definitely a lot going on that we hope to share as soon as the data are available. Dr. Mohamed Salem: We'll be looking forward to your next presentation and seeing that. So again, most of your work showed us that we really have to choose the right patient with the right target for the right treatment to achieve the best possible outcome. So we're getting short on time here. But before we conclude, ASCO Daily News Podcast has a huge audience of oncologists, I wanted to give you the chance to share anything you'd like to share with our audience today before we finish. Dr. Cercek? Dr. Andrea Cercek: I believe this is an incredibly exciting time in colorectal cancer. I think it's finally our turn, which feels really nice, and obviously, we have a lot more work that needs to be done. But my personal belief is to keep trying to chip away at the pie and identify responders and keep working to have better-targeted drugs and better treatment options that will improve responses and improve outcomes for our patients. But I certainly believe that we are well on our way there, and it's very exciting. Dr. Mohamed Salem: I totally agree. Dr. Chalabi, any thoughts? Dr. Myriam Chalabi: I think after 2022 and the data that we've been showing, I think it's important to– and I think by now, maybe it's not even necessary anymore to say it– but I think it's important to really look at the tumors and look at these MMR proteins or MSI, and to make sure that you're treating the patient in the right way, and to consider that. Before, it wasn't as important in the neoadjuvant setting or these localized tumors, but now it's becoming essential.  And I think if you would have looked five years ago and you would say, yeah, these MSI tumors are important to find, it's a very small proportion of patients, in rectal cancer even lower than in colon cancer. But still, it has such a huge impact on what you're doing in these patients and your chances of cure. So I think that would be my most important giveaway to test for MMR deficiency before deciding on a treatment for your patients. And we're working on trials with neoadjuvant immunotherapy. Also in other tumor types, Dr. Cercek is also doing the same. I think those will be very important also outside of the GI field to see whether this approach works for a much larger patient population, despite the low incidence.  Dr. Andrea Cercek: Dr. Chalabi just made a critical point that that is most important is to remember that we do have biomarkers in colorectal cancer that, in the neoadjuvant setting and in the metastatic setting, especially MSI, that we need to test for. And then, just to add from a clinical perspective, in rectal cancer, the large majority of patients that have mismatch-repair deficient or MSI tumors actually have Lynch syndrome. So really, if you identify a patient that's mismatch-repair deficient or MSI-high anywhere, but especially in the rectum, they absolutely should get germline testing. Dr. Mohamed Salem: I echo that and second that. And Dr. Cercek, thank you, and I know you did a lot of work in colorectal cancer in the younger adult population, too, so I think you've had a huge impact on that area too. I would like to thank both of you again for being here today, but more for the great work you and your teams are doing to advance the field. It's really a very exciting time in GI cancers now, and thank you so much for your work and for sharing your insights with us today on the ASCO Daily News Podcast. Dr. Myriam Chalabi: Thank you so much for having me. It's been great. Dr. Andrea Cercek: Thank you for having me. Dr. Mohamed Salem: Of course, and thanks to our listeners for your time today. If you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much. Disclaimer: 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. Find out more about today's speakers:     Dr. Mohamed Salem @SalemGIOncDoc   Dr. Myriam Chalabi @MyriamChalabi   Dr. Andrea Cercek @AndreaCercek   Learn about other key advances in GI Oncology: SWOG 1815, PARADIGM, and Other Advances at GI23   Follow ASCO on social media:      @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:   Dr. Mohamed Salem: Consulting or Advisory Role: Taiho Pharmaceutical, Exelixis, Bristol-Myers Squibb, Exelixis, QED Therapeutics, Novartis, Pfizer, Daiichi Sankyo/Astra Zeneca Speakers' Bureau: Genentech/Roche, Taiho Pharmaceutical, Daiichi Sankyo/Astra Zeneca, BMS, Merck Dr. Myriam Chalabi: Consulting or Advisory Role: MSD, Bristol-Myers Squibb/Celegne, Numab Research Funding (Institution): Bristol-Myers Squibb, Roche/Genentech, MSD Travel, Accommodations, Expenses: Roche/Genentech, Bristol-Myers Squibb Dr. Andrea Cercek: Consulting or Advisory Role: Bayer, GSK, Incyte, Merck, Janssen, Seattle Genetics, G1 Therapeutics Research Funding (Institution): Seattle Genetics, GSK, Rgenix          

Drs. Lediana Goduni, Safa Rahmani, and Marianeli Rodriguez join to discuss four recent publications in major ophthalmology journals.Posterior Vitreous Detachments and Complications (https://ophthalmologyretina.org/article/S2468-6530(22)00575-9/fulltext)Tractional Retinal Detachments, Treatment Type, and Follow-up (https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2799232)Ranibizumab versus Bevacizumab for ROP (https://www.aaojournal.org/article/S0161-6420(22)00904-6/fulltext)Patient Satisfaction Metrics (https://jamanetwork.com/journals/jama/article-abstract/2798954)Relevant Financial Disclosures: None relevantYou can now claim CME credits via the AAO website. Visit https://www.aao.org/browse-multimedia?filter=Audi

Interview with David W. Hutton, PhD, author of Cost-effectiveness of Aflibercept Monotherapy vs Bevacizumab First Followed by Aflibercept If Needed for Diabetic Macular Edema. Hosted by Neil Bressler, MD.

Interview with David W. Hutton, PhD, author of Cost-effectiveness of Aflibercept Monotherapy vs Bevacizumab First Followed by Aflibercept If Needed for Diabetic Macular Edema. Hosted by Neil Bressler, MD.

Discussing GI ASCO 2023 Highlights - practice changing/informing studies with Dr. Mark Lewis, a Cancer Survivor, Director of GI Oncology at Intermountain Healthcare. SPOTLIGHT - Zolbetuximab with mFOLFOX6 Meets Primary Endpoint NAPOLI3 - Randomized Phase III study of first-line liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin versus nab-paclitaxel + gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma Analysis of the impact of eliminating bolus 5-fluorouracil in metastatic colon cancer MOUNTAINEER - FDA approval of tucatinib combined with trastuzumab for HER2-positive metastatic colorectal cancer SUNLIGHT - Trifluridine/Tipiracil plus Bevacizumab provides benefit in refractory metastatic colorectal cancer Website: http://www.oncbrothers.com/ Twitter: https://twitter.com/oncbrothers Contact us at info@oncbrothers.com

In this episode of the IJGC podcast, Editor-in-Chief, Dr. Pedro Ramirez, is joined by Professors Jacobus Pfisterer and Philipp Harter to discuss prolonged maintenance with bevacizumab. Prof. Philipp Harter is the director of the Department of Gynecology & Gynecologic Oncology at Kliniken Essen-Mitte in Essen, Germany and the chair of the AGO Study Group. Prof. Jacobus Pfisterer is Director of the Gynecologic Oncology Center in Kiel Germany and former chair of the AGO Study Group. Highlights: - 30-month bevacizumb maintenance does not improve progression-free survival nor overall survival in advanced ovarian cancer. - 30-month bevacizumb maintenance is associated with more adverse events compared to 15 months. - 15-month bevacizumb maintenance remains standard of care.

A new research paper was published in Oncotarget's Volume 13 on December 6, 2022, entitled, “Plasma growth hormone is a potential biomarker of response to atezolizumab and bevacizumab in advanced hepatocellular carcinoma patients.” Hepatocellular carcinoma (HCC) has limited systemic therapy options when discovered at an advanced stage. Thus, there is a need for accessible and minimally invasive biomarkers of response to guide the selection of patients for treatment. In this new study, researchers Yehia I. Mohamed, Dan G. Duda, Muhammad O. Awiwi, Sunyoung S. Lee, Lina Altameemi, Lianchun Xiao, Jeffrey S. Morris, Robert A. Wolff, Khaled M. Elsayes, Rikita I. Hatia, Aliya Qayyum, Shadi M. Chamseddine, Asif Rashid, James C. Yao, Armeen Mahvash, Manal M. Hassan, Hesham M. Amin, and Ahmed Omar Kaseb from MD Anderson Cancer Center, Massachusetts General Hospital, Harvard Medical School, Michigan State University, University of Pennsylvania, and Perelman School of Medicine investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev). “The present study was designed to investigate the association between GH levels and overall survivals (OS) and progression free survival (PFS) in HCC patients treated with current standard, atezolizumab plus bevacizumab.” The study included unresectable HCC patients scheduled to receive Atezo/Bev. Patients were followed to determine progression-free survival (PFS) and overall survival (OS). Plasma GH levels were measured by ELISA and used to stratify the HCC patients into GH-high and GH-low groups (the cutoff normal GH levels in women and men are ≤3.7 μg/L and ≤0.9 μg/L, respectively). The Kaplan-Meier method was used to calculate median OS and PFS and Log rank test was used to compare survival outcomes between GH-high and -low groups. Thirty-seven patients were included in this analysis, of whom 31 were males and 6 females, with a median age of 67 years (range: 37–80). At the time of the analysis, the one-year survival rate was 70% (95% CI: 0.51, 0.96) among GH low patients and 33% (95% CI: 0.16, 0.67) among GH high patients. OS was significantly superior in GH-low compared to GH-high patients (median OS: 18.9 vs. 9.3 months; p = 0.014). PFS showed a non-significant trend in favor of GH-low patients compared to the GH-high group (median PFS: 6.6 vs. 2.9 months; p = 0.053). “Plasma GH is a biomarker candidate for predicting treatment outcomes in advanced HCC patients treated with Atezo/Bev. This finding should be further validated in larger randomized clinical trials in advanced HCC patients.” DOI: https://doi.org/10.18632/oncotarget.28322 Correspondence to: Ahmed Omar Kaseb - akaseb@mdanderson.org Keywords: growth hormone, hepatocellular carcinoma, immunotherapy, atezolizumab, bevacizumab About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.

In this episode, Prof Isabelle Ray Coquard, MD, PhD, and Ignace Vergote, MD, PhD, share their thoughts on key studies of interested presented at the 2022 ESGO annual meeting in Berlin, Germany, including:• Phase III CALLA trial of durvalumab combined with and following chemoradiotherapy in locally advanced cervical cancer  • Geneva HRD test: validation of samples from PAOLA-1 dataset using Geneva laboratory–developed test  • Validation of NOGGO-GIS HRD assay using samples from the PAOLA-1 trial  • Survival results from phase III ARIEL3: maintenance rucaparib vs placebo following response to platinum-based chemotherapy for recurrent ovarian cancerPresenters:Isabelle Ray-Coquard, MD, PhDProfessor of Department of Medical OncologyClinical Science Institute of the Léon Bérard CenterLyon, France  Ignace Vergote, MD, PhDProfessor Em. of Department of Obstetrics and Gynecologic OncologyUniversity Hospitals LeuvenLeuven, BelgiumContent supported by educational grants from AstraZeneca, GlaxoSmithKline, Karyopharm Therapeutics, and Merck Sharp & Dohme Corp.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries: https://bit.ly/3SSSqpN  

The Journal RETINA is devoted exclusively to diseases of the retina and vitreous. These podcasts are intended to bring to its listeners summaries of selected articles published in the current issue of this internationally acclaimed journal.

Dr. Jhavery discusses results of DRCR Retina Protocol AC study which compared DME response to anti-VEGF injections in patients who received Aflibercept monotherapy vs those who started with Bevacizumab first and then switched to Aflibercept if needed.  Discussed article: Jhaveri CD, Glassman AR, Ferris FL 3rd, Liu D, Maguire MG, Allen JB, Baker CW, Browning D, Cunningham MA, Friedman SM, Jampol LM, Marcus DM, Martin DF, Preston CM, Stockdale CR, Sun JK; DRCR Retina Network. Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema. N Engl J Med. 2022 Aug 25;387(8):692-703. doi: 10.1056/NEJMoa2204225. Epub 2022 Jul 14. PMID: 35833805.

In this episode,Susana Banerjee, MBBS, MA, PhD, and Mansoor Raza Mirza, MD, share their thoughts on key studies of interested presented at the IGCS 2022 Annual Global Meeting for ovarian and cervical cancers including:Post-hoc analyses from SOLO-3: olaparib vs physician's choice chemotherapy in germline BRCA mutant platinum-sensitive recurrent ovarian cancerPhase III CALLA trial: durvalumab combined with and following chemoradiation for locally-advanced cervical cancerPhase III ARIEL3: final OS for maintenance rucaparib vs placebo following response to platinum-based chemotherapy for recurrent high-grade serous ovarian cancerRetrospective NeCTuR study: outcomes with topotecan, paclitaxel, and bevacizumab (TPB) vs non-TPB regimens for recurrent high-grade neuroendocrine carcinoma of the cervixPresenters:Susana Banerjee, MBBS, MA, PhD, FRCPConsultant Medical Oncologist and Research LeadGynaecology UnitRoyal Marsden NHS Foundation TrustLondon, United KingdomMansoor Raza Mirza, MDChief OncologistDepartment of OncologyRigshopitalet – Copenhagen University HospitalCopenhagen, DenmarkContent supported by educational grants from AstraZeneca, GlaxoSmithKline, Karyopharm Therapeutics, and Merck Sharp & Dohme Corp.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries:https://bit.ly/38xuRBv

In this episode, Domenica Lorusso, MD, PhD, and Alexandra Leary, MD, PhD, provide their expert insights on key updates presented for ovarian cancer trials including:Phase III GOG-3004/SOLO-1: OS results after 7 years of follow-up for patients with newly diagnosed advanced ovarian cancer receiving maintenance olaparib vs placeboPhase III ENGOT-ov25/PAOLA-1: final OS results from the trial of maintenance therapy with olaparib with bevacizumab vs bevacizumab alone in women with newly diagnosed advanced ovarian cancerPhase III ATHENA-MONO: outcomes by disease subgroups receiving rucaparib vs placebo maintenance after platinum-based chemotherapy in patients with newly diagnosed advanced ovarian cancerPhase III ARIEL4: OS outcomes following treatment with rucaparib vs chemotherapy in patients with relapsed advanced ovarian cancer and a deleterious BRCA1/2 mutationPresenters:Domenica Lorusso, MD, PhDAssociate ProfessorGynecologic Oncology DepartmentClinical Research UnitFondazione Policlinico Gemelli IRCCSRome, ItalyAlexandra Leary, MD, PhDMedical Oncologist and Team LeaderGynecology Translational Research LabDepartment of MedicineGustave Roussy Cancer CenterParis, FranceContent supported by educational grants from AstraZeneca, GlaxoSmithKline, Karyopharm Therapeutics, and Merck Sharp & Dohme Corp.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries: https://bit.ly/3SSSqpN

In this episode, Ryan D. Gentzler, MD, MS, and Jonathan Riess, MD, MS, answer audience questions on managing EGFR-mutated non-small-cell lung cancer (NSCLC) from a live meeting series. The episode includes expert insights on:• Identifying patients who may benefit the most from adjuvant osimertinib  • Testing for EGFR mutations in early-stage NSCLC• Critical importance of getting molecular test results before starting immunotherapy• Monitoring cardiac toxicity in patients receiving osimertinib• Key ongoing trials in EGFR-mutated NSCLC for patients with newly diagnosed disease and following progression on osimertinibPresenters:Ryan D. Gentzler, MD, MSAssociate ProfessorDivision of Hematology/OncologyDepartment of MedicineUniversity of VirginiaThoracic Medical OncologistUniversity of Virginia Comprehensive Cancer CenterCharlottesville, VirginiaJonathan Riess, MD, MSAssociate ProfessorDepartment of Internal Medicine/Hematology-OncologyUniversity of California, DavisMedical Director, Thoracic OncologyUniversity of California, Davis Comprehensive Cancer CenterSacramento, CaliforniaLink to full program: https://bit.ly/3DZGzSO  

Drs. Shriji Patel, Safa Rahmani, and Sarwar Zahid join for a journal club discussion of three recent publications in major ophthalmology journals:Aflibercept or Bevacizumab First for Diabetic Macular Edema (https://www.nejm.org/doi/full/10.1056/NEJMoa2204225)Gas Tamponade for Postoperative Vitreous Hemorrhage Prevention (https://www.ajo.com/article/S0002-9394(22)00251-3/fulltext)Positioning after Macular Hole Surgery (https://ophthalmologyretina.org/article/S2468-6530(22)00322-0/fulltext)Relevant Financial Disclosures: Dr. Sridhar is a consultant for Alcon, DORC, Genentech, and Regeneron. Drs. Patel, Rahmani, and Zahid have no relevant disclosures.You can now claim CME credits via the AAO website. Visit https://www.aao.org/browse-multimedia?filter=Audi

Drs Sumanta Pal and Brian Rini discuss front-line treatment of renal cell carcinoma. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968736). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Bevacizumab Plus Interferon-alpha Versus Interferon-alpha Monotherapy in Patients With Metastatic Renal Cell Carcinoma: Results of Overall Survival for CALGB 90206 https://ascopubs.org/doi/10.1200/jco.2009.27.18_suppl.lba5019 An updated table of the front-line IO combination RCC studies that have shown an OS advantage https://twitter.com/brian_rini/status/1309609380585844736/photo/1 Targeting PD-1 or PD-L1 in Metastatic Kidney Cancer: Combination Therapy in the First-Line Setting https://aacrjournals.org/clincancerres/article/26/9/2087/83102/Targeting-PD-1-or-PD-L1-in-Metastatic-Kidney Conditional Survival and Long-term Efficacy With Nivolumab Plus Ipilimumab Versus Sunitinib in Patients With Advanced Renal Cell Carcinoma https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34180 International Metastatic Renal Cell Carcinoma Database Consortium Criteria https://www.uptodate.com/contents/image?imageKey=ONC%2F116130&topicKey=ONC%2F2984&source=see_link Molecular Correlates Differentiate Response to Atezolizumab (atezo) + Bevacizumab (bev) vs Sunitinib (sun): Results From a Phase III Study (IMmotion151) in Untreated Metastatic Renal Cell Carcinoma (mRCC) https://cslide.ctimeetingtech.com/esmo2018/attendee/confcal/presentation/list?q=LBA31 Nivolumab Versus Everolimus in Patients With Advanced Renal Cell Carcinoma: Updated Results With Long-term Follow-up of the Randomized, Open-Label, Phase 3 CheckMate 025 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415096/pdf/nihms-1732721.pdf Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma https://www.nejm.org/doi/10.1056/NEJMoa2035716 The Uromigos Debate: Treatment of Favorable Risk Renal Cancer https://anchor.fm/the-uromigos/episodes/Episode-67-The-Third-Uromigos-Debate---fPD1VEGF-vs-PD1CTLA4-for-front-line-renal-cancer-emjpji Health-Related Quality-of-Life Outcomes in Patients With Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab or Everolimus Versus Sunitinib (CLEAR): A Randomised, Phase 3 Study https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00212-1/fulltext Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (COSMIC-313) https://clinicaltrials.gov/ct2/show/NCT03937219 A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012) https://clinicaltrials.gov/ct2/show/NCT04736706 Twitter poll questions: What magnitude of benefit is required to adopt triplets? OS https://mobile.twitter.com/brian_rini/status/1508450496104783877 What magnitude of absolute PFS benefit vs doublets is required to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508450910506295305 What would be the most convincing endpoint to adopt triplets? https://mobile.twitter.com/brian_rini/status/1508451622564909057 Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436590/ OPtimal Treatment by Invoking biologic Clusters in Renal Cell Carcinoma (OPTIC RCC) https://www.kcameetings.org/wp-content/uploads/2021/12/IKCSNA21_TIP8_Chen.pdf

In this podcast episode from Clinical Care Options (CCO), Heinz-Josef Klumpen, MD, PhD, and Chris Verslype, MD, PhD, discuss challenges in selecting and sequencing therapy for patients with advanced hepatocellular carcinoma. Topics include:Factors to consider before selecting frontline immunotherapyRole of TKIs in the frontlineImpact of Child-Pugh status on the efficacy of immunotherapy/VEGF inhibitor combination therapyReal-world evidence on frontline immunotherapy/VEGF combination therapyFactors to consider when selecting second-line therapy including the role of TKIs and planning for multiple lines of therapyPresenters:Heinz-Josef Klumpen, MD, PhDStaff Specialist, Medical OncologistDepartment of Medical OncologyAmsterdam UMCAmsterdam, The NetherlandsChris Verslype, MD, PhDProfessorClinical Digestive OncologyKULeuvenHead of ClinicHepatologyDigestive OncologyU.Z. LeuvenLeuven, Belgium

In this episode, Jubilee Brown, MD, and Elisabeth Diver, MD, provide expert insights on new data presented at ASCO 2022 for ovarian, endometrial, and cervical cancers regarding:Subgroup analyses from KEYNOTE-826 evaluating pembrolizumab in combination with chemotherapy with or without bevacizumab in persistent, recurrent, or metastatic cervical cancerPreliminary subgroup analyses from phase III ENGOT-EN5/GOG-3055 SIENDO trial of selinexor vs placebo maintenance in recurrent endometrial cancerUpdated analyses from phase I GARNET trial of dostarlimab in dMMR/MSI-H and pMMR/MSS advanced/recurrent endometrial cancer (cohorts A1 and A2)EndoBARR trial of atezolizumab, bevacizumab, and rucaparib in previously treated recurrent and progressive endometrial cancerPhase III ATHENA-MONO trial of first-line rucaparib vs placebo maintenance after platinum-based chemotherapy in patients with advanced ovarian cancerPresenters:Jubilee Brown, MDProfessor and Division DirectorGynecologic OncologyLevine Cancer Institute, Atrium HealthCharlotte, North CarolinaElisabeth Diver, MDClinical Assistant ProfessorDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyStanford UniversityStanford Cancer InstituteStanford University Hospital and ClinicsStanford, CaliforniaContent supported by educational grants from AstraZeneca, GlaxoSmithKline, Karyopharm Therapeutics, and Merck Sharp & Dohme Corp.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries:https://bit.ly/3ufB8Js

Prof. dr. Kees Punt, hoogleraar Medische Oncologie in het Julius Centrum verbonden aan het UMC Utrecht, bespreekt de DCCG CAIRO5-studie die hij presenteerde tijdens de 2022 ASCO Annual Meeting. Aan bod komen onder andere de achtergrond van de studie, rol van expert leverpanel en de resultaten.

In this episode, Nilofer S. Azad, MD, and Kanwal Raghav, MD, discuss current and emerging uses of regorafenib and TAS-102 in later-line treatment of patients with mCRC, with topics including:Current use of regorafenib and TAS-102 monotherapyCombination therapy with regorafenib and PD-1 inhibitorsAdding bevacizumab to TAS-102Presenters:Nilofer S. Azad, MD  Professor, Oncology  Sidney Kimmel Comprehensive Cancer Center  Johns Hopkins UniversityBaltimore, Maryland  Kanwal Raghav, MDAssociate Professor, GI Medical Oncology  University of Texas MD Anderson Cancer CenterHouston, Texas  Content based on an online CME program supported by an educational grant from Bayer HealthCare Pharmaceuticals Inc.Follow along with the slideset:https://bit.ly/3NLejWeLink to full program:https://bit.ly/33yrIyh

In this first episode of two podcasts, Dr. Amit Singal and Dr. Mark Yarchoan discuss the latest data supporting their approach to selecting treatment regimens for patients with HCC, with topics including: the current challenges in the management of HCC, recommended initial workup strategies and the evolving treatment landscape in HCC. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Amit Singal, MD, MSMark Yarchoan, MDBridget O'Brien, DNP, FNP-BC, AOCNPDr Singal: consulting fees: AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Roche.Dr Yarchoan: consulting fees: AstraZeneca, Eisai, Exelixis, Genentech; other financial or material support: Bristol-Myers Squibb, Incyte.Dr O'Brien: fees for non-CME/CE services: Amgen, Novartis.

In this second episode of two podcasts, Dr. Amit Singal and Dr. Mark Yarchoan discuss how to identify, prevent and mitigate treatment-related adverse events, and review cases with careful considerations for patient-specific factors guiding treatment selection, followed by a question-and-answer session on the management of patients with HCC. This activity is available for CE/CME credit. Claim your credit at pce.is/GIGU.Contributors:Amit Singal, MD, MSMark Yarchoan, MDBridget O'Brien, DNP, FNP-BC, AOCNPDr Singal: consulting fees: AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech, Roche.Dr Yarchoan: consulting fees: AstraZeneca, Eisai, Exelixis, Genentech; other financial or material support: Bristol-Myers Squibb, Incyte.Dr O'Brien: fees for non-CME/CE services: Amgen, Novartis.

In this podcast episode from Clinical Care Options (CCO), Josep M. Llovet, MD, PhD, and Markus Peck-Radosavljevic, MD, MBA, discuss second line treatment of patients with advanced hepatocellular carcinoma. Topics include:Available agents for the management of advanced hepatocellular carcinoma in the second lineThe current role of tyrosine kinase inhibitors in second-line treatment of advanced hepatocellular carcinomaOngoing clinical trials in the second-line settingPresenters:  Josep M. Llovet, MD, PhD, FAASLDProfessor of MedicineDirector, Mount Sinai Liver Cancer ProgramDivision of Liver DiseasesMount Sinai School of MedicineNew York, New YorkProfessor of ResearchLiver Unit, IDIBAPSHospital Clinic BarcelonaBarcelona, SpainUniv. Prof. Markus Peck-Radosavljevic, MD, MBAProfessor of MedicineMedical University of ViennaVienna, AustriaDepartment Chair, Innere Medizin und GastroenterologieKlinikum Klagenfurt am WörtherseeKlagenfurt am Wörthersee, AustriaLink to full program, including accompanying downloadable slidesets:https://bit.ly/2ZL9bxq

Description: Metachronous colorectal liver metastasis (CRLM) is a complex clinical situation requiring multidisciplinary management. In this episode from the Hepato-Pancreato-Biliary team at Behind the Knife, we discuss a patient presenting with metachronous CRLM and how management may change with varying clinical scenarios.  Learning Objectives: In this episode, we review the initial workup and pre-operative considerations in a patient presenting with metachronous CRLM.  We discuss key aspects of resectability of CRLM, including physiologic and hepatic fitness, biology of the disease, and technical considerations.  We review the timing and common regimens of systemic treatment for differing clinical scenarios, as well as when adjuncts to treatment may be useful (e.g., portal venous embolization).  Finally, we highlight important aspects of intraoperative and postoperative management. Hosts: Timothy Vreeland, MD, FACS (@vreelant) is an Associate Professor of Surgery at the Uniformed Services University of the Health Sciences and Surgical Oncologist at Brooke Army Medical Center Daniel Nelson, DO, FACS (@usarmydoc24) is an Associate Professor of Surgery at the Uniformed Services University of the Health Sciences and Surgical Oncologist at William Beaumont Army Medical Center Connor Chick, MD (@connor_chick) is a PGY-5 General Surgery resident at Brooke Army Medical Center Lexy (Alexandra) Adams, MD, MPH (@lexyadams16) is a PGY-4 General Surgery resident at Brooke Army Medical Center Beth (Elizabeth) Carpenter, MD (@elizcarpenter16) is a PGY-3 General Surgery resident at Brooke Army Medical Center  Links to Papers Referenced in this Episode: NCCN Guidelines for Colon Cancer https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf Mutation Status of RAS, TP53, and SMAD4 is Superior to Mutation Status of RAS Alone for Predicting Prognosis after Resection of Colorectal Liver Metastases. Clin Cancer Res. 2019 Oct 1;25(19):5843-5851. doi: 10.1158/1078-0432.CCR-19-0863. Epub 2019 Jun 20. PMID: 31221662; PMCID: PMC6774854. https://pubmed.ncbi.nlm.nih.gov/31221662/ Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1208-15. doi: 10.1016/S1470-2045(13)70447-9. Epub 2013 Oct 11. PMID: 24120480. https://pubmed.ncbi.nlm.nih.gov/24120480/ FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015 Oct;16(13):1306-15. doi: 10.1016/S1470-2045(15)00122-9. Epub 2015 Aug 31. PMID: 26338525. https://pubmed.ncbi.nlm.nih.gov/26338525/ Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM). Oncologist. 2019 Jul;24(7):921-932. doi: 10.1634/theoncologist.2018-0344. Epub 2018 Dec 14. PMID: 30552157; PMCID: PMC6656450. https://pubmed.ncbi.nlm.nih.gov/30552157/ Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol. 2015 Apr;26(4):702-708. doi: 10.1093/annonc/mdu580. Epub 2014 Dec 23. PMID: 25538173. https://pubmed.ncbi.nlm.nih.gov/25538173/ Recommended Additional Podcasts on CRLM: The AHPBA Podcast: 1.     Episode 1: Dr. Jean Nicolas Vauthey - Colorectal Liver Metastases (https://podcasts.apple.com/us/podcast/episode-1-dr-jean-nicolas-vauthey-colorectal-liver/id1501441845?i=1000467381474) 2.     Episode 12:Dr D'Angelica - Colorectal Liver Metastases and Hepatic Artery Infusion Pumps (https://podcasts.apple.com/us/podcast/episode-12-dr-dangelica-colorectal-liver-metastases/id1501441845?i=1000521718184) Behind the Knife: 1.     Surgical Oncology-Hepatic Artery Infusion Pump (https://podcasts.apple.com/ye/podcast/surgical-oncology-hepatic-artery-infusion-pump/id980990143?i=1000525833877) Please visit behindtheknife.org to access other high-yield surgical education podcasts, videos and more.  

Interview with Robert J. Motzer, MD, author of Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. Hosted by Jack West, MD.

Dr. Iyad Alnahhas interviews Drs. Vinay Puduvalli and Ying Yuan about their paper "A Bayesian adaptive randomized phase II multicenter trial of bevacizumab with or without vorinostat in adults with recurrent glioblastoma" published in Neuro-Oncology in March 2020

Dr. Philip Hykin discusses the LEAVO trial which was a large prospective trial comparing the efficacy of three main anti-VEGF intravitreal injections (bevacizumab, ranibizumab and aflibercept) for treating macular edema secondary to Central Retinal Vein Occlusion. The discussed article: Clinical Effectiveness of Intravitreal Therapy With Ranibizumab vs Aflibercept vs Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion: A Randomized Clinical Trial. Hykin P, Prevost AT, Vasconcelos JC, Murphy C, Kelly J, Ramu J, Hounsome B, Yang Y, Harding SP, Lotery A, Chakravarthy U, Sivaprasad S; LEAVO Study Group. JAMA Ophthalmol. 2019 Aug 29. doi:10.1001/jamaophthalmol.2019.3305.

This week, we summarize two studies presented at the recent ESMO Asia Congress—one on a novel combination therapy for unresectable liver cancer, and the second on the activity of a Chinese-manufactured trastuzumab biosimilar. We'll also discuss last week's FDA approval of acalabrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma.Coverage of stories discussed this week on ascopost.com:ESMO Asia 2019: Combination of Atezolizumab and Bevacizumab for Unresectable Hepatocellular CarcinomaESMO Asia 2019: Trastuzumab Biosimilar HLX02 Shows Activity in HER2-Positive Metastatic Breast CancerFDA Approves Acalabrutinib for CLL/SLL as Part of Project Orbis

According to findings from a phase II trial, the combination of nivolumab and bevacizumab has shown activity in relapsed ovarian cancer—we discuss those findings reported in JAMA Oncology. Next, we'll move on to a session from CHEST 2019 which outlined palliation techniques that may be of use to oncologists and pulmonologists in treating patients with end-stage lung cancer. Finally, we'll discuss two recent FDA drug approvals for patients with hematologic disorders.Coverage of stories discussed this week on ascopost.com:Nivolumab Plus Bevacizumab in Relapsed Ovarian CancerWhat Is the Best Palliation for End-Stage Lung Cancer?FDA Grants Accelerated Approval to Zanubrutinib for Pretreated Mantle Cell LymphomaFDA Approves Luspatercept-aamt for Anemia in Patients With Beta Thalassemia