Chapters Transcript Video Update on Metastatic Urothelial Carcinoma Back to Symposium Dr. Ghatalia discusses updates on Metastatic Urothelial Carcinoma. Hi everyone. My name is pushpa natalia. And today I'll be giving you an update about metastatic curatorial cancer in uh just a few minutes. Um so as everyone knows this platinum based chemotherapy with those dents and back or genocide being cis platinum have been the first line standard of care treatment for metastatic curatorial cancer patients for a long time now. And that's based on these historic clinical trials where an overall response rate of about 50-70%, including a cr rate of about 15-20% is seen in patients as you can see based on the tail of the carving these graphs. Uh however, uh the question is whether based on some of the newer data that have come out in 2020 has the standard of care. First line treatment changed any and the quick answer is no. And I'm going to have some data to show that. So in vigor 1 30 was a phase three clinical trial in patients with frontline setting for metastatic your material cancer where patients got randomized to uh I owe chemo with kessel is a map plus chemo. And the chemo included either jim side of being systematic nor James had been carbo platinum versus I alone versus placebo class chemotherapy. And one of the clinical trial primary endpoints was progression free survival and overall survival comparing patients getting I. O. Plus chemo versus chemo alone. And as you can see on the left, the final result of the median progression free survival. They were it was considered positive, positive but there was just a two months E. F. S. Benefit. And on the right, the interim median overall survival results have so far not been shown to be so promising and based on that we don't necessarily give combination of I O. T. G I in the front line setting in clinical practice at this point. Another primary and part of the study was overall survival comparing patients getting immunotherapy versus uh chemotherapy immunotherapy single agent. And uh as you can see her that initially patients getting chemotherapy or doing better. And then after about 12 months, the curves crossed. Uh the FDA had issued a mandate last year uh based on some of the early results of the study, where they were concerned that patients receiving single agent immunotherapy may not be doing so well in the front line setting. And so further analysis of those graphs actually showed that patients who are Pd L one negative that you can see on the right. That separation was much more pronounced compared to patients who are Pd L. One positive. And based on that in patients who assist latin ineligible in the front line setting based on the F. D. A. Mandate. Uh If they were PD L. One negative, but if they were eligible for platinum based chemotherapy then they should receive receive combination treatment with carbo platinum gem side of being. Uh But if they were PD L. One negative and not eligible for platinum based treatment, then immunotherapy can be considered Another clinical trial. Looking at frontline treatment. He north 361 was recently presented at as more and very similar design to the previous one. Except that you're the use Federalism MAB with chemotherapy versus chemotherapy versus Federalism. My balloon. Unfortunately Another more than 1000 patient study uh was negative although numerically the PFS and OS are better with the I. O. Chemo combination. It did not meet the boundary for significance. And there's another negative clinical trial. Um uh There was another clinical trial that I'm not going to be presenting named Danube which also looked at frontline to really um optimal um Ahmad versus Darrell Hammond versus chemotherapy which was again a big clinical trial that was negative. And so the frontline standard of care treatment for patients with metastatic your material cancer at this point remains CISplatin based chemotherapy. Uh huh. What about maintenance immunotherapy? So clinical trial that was presented recently named Javelin 100 had patients who received CISplatin based chemotherapy in the front line setting. Or actually even carbo platon gem carbo platon. And if those patients had either a C. R. P. R. Or stable disease with that particular combination then patients went on to receive maintenance immunotherapy with Vilma versus best supportive care. This was a 700 patients study with a primary and point of overall survival in all patients and PDF. One positive patients. This was a positive study and practice changing and patients who received maintenance A value map had about a seven month improvement in their overall survival. Uh of note in this clinical trial, there was no crossover. Um and about 50% of patients on the best supportive care did not end up receiving immunotherapy alone. Based on the fact that this trial was opening a lot of countries outside of the US. And um there was benefit noted in both Pd L. One positive and negative patients, although the benefit was greater in the PD L. One positive patients. Another clinical trial looking at the same similar question was by the Hoosier Oncology group and uh they used maintenance federalism mab versus placebo. And although the median overall survival here, the curves don't don't separate out so much. Uh It should be noted that this was a small study with about 100 patients and crossover was allowed. So a lot of patients on placebo did end up getting immunotherapy later. Uh The progression free survival graphs of this particular study, they did separate out and so maintenance immunotherapy should be considered to delay progression and especially in patients where progression will be symptomatic and you certainly don't want that or if there is a patient where you are not sure if uh they will be able to receive immuno therapy in the in the uh second line or future line uh step setting, moving on to the second line therapy for metastatic material cancer. There's a lot to talk pure and I'm going only going to be talking about some of the treatments listed here. Uh So everyone knows about the pd one pd L one therapy and there are five currently approved pt one pd L. One therapies that are used for metastatic curatorial cancer patients. Um And the response rate of these studies have been around 15 to 20%. It's interesting that recently data from a combination of new volume map and papilloma map study uh was recently published. And in this particular study, patients who progressed on platinum based therapy with in new york or who were not chemotherapy candidates received the volume app versus two different doses of Nero and hippie Nero three plus 81 or never, one plus 83 for four cycles followed by the volume at maintenance. Um And I find I find the results of this study intriguing, especially in patients receiving no volume app one plus diplomat three mg per kilogram dozing where uh a response rate of about 38% and uh an improvement in overall survival was also noted. However, this drug combination is not currently every year approved and more mature results are awaited. Uh Another new drug, which is not so new anymore is in Fort Mac video button which is an antibody drug. Conjugate where the antibody is directed against necked and four next and four is a protein very commonly present in your ethereal cancer patients. And E. V. Is attached to a particular drug mm. A which is like a chemotherapy agent on binding to next and for the drug delivers the chemotherapy component inside the bladder cancer cells and causes apoptosis. Uh There have been a lot of ongoing clinical trials using in Fort um Advil Gotten. Um and I'm not going to be able to go into each of these But to start with The one of the studies, every two or 1 looked at patients in the receiving immunotherapy and chemotherapy and then progressing and showed uh an impressive response rate. Uh And another clinical trial in the face. Three settings also showed uh an overall response rate that is positive in the study uh Find the outcomes are not yet out. It was just a positive press release E. V. 21 cohort to included patients in the second line setting, post immunotherapy and also showed an overall response rate that was in the 50% range. Uh And most recently, E. V. 103 is a clinical trial in the front line setting for patients who are CISplatin ineligible and received E. V. Plus. Pembroke is a map and had a very impressive response rate of 73%. Uh In Fort McMurray. Horton Plus Federalism had was granted FD breakthrough designation recently. Uh E. V. Is a medication with quite a few side effects uh not as easy to tolerate. Um And about 60% of patients on these studies did end up having some of the other 33 side effects. The most commonly fatih alopecia and neuropathy have been seen with this particular drug. Um I'm not gonna have time to go into order fitness, which is an f g f R inhibitor. Uh And society is um Abdal gluten, which is an anti troop to antibody drug conjugate, which uh has also shown very promising results. Um And so the last two summary points are that second line treatment options that are currently available for patients with metastatic curatorial cancer include all the fitness, especially in patients who have f g f R three mutations and fusions in Fordham Advil Houghton and future promising treatment options include uh P. T. One C D. L. A. Foreign better combinations and systems A map Go over it again. Thank you very much for the opportunity to present today. Created by Related Presenters Pooja Ghatalia, MD Assistant Professor, Department of Hematology/Oncology Assistant Professor, Department of Hematology/OncologyCollaborating Member, Cancer Epigenetics
