Article: Transcript: EV-301 Stats: A Cheat Sheet for Oncologists Treating Urothelial Cancer - Jonathan E. Rosenberg, MD @DrRosenbergMSK @MSKCancerCenter @AstellasUS @Seage...
Enfortumab Vedotin was tested in a randomized phase 3 trial in patients with metastatic urothelial cancer who had previously received platinum chemotherapy and an immune checkpoint inhibitor and here we present updated data from the 24-month two-year follow-up for patients with advanced disease and I think the state is very important because it shows us that there are a proportion of patients who have durable responses the the survival rate at five years for metastatic bladder cancer has historically been around five percent and this and we've certainly seen some improvements although still not where it needs to be the data reported at ASCO showed a continued improvement in overall survival for patients treated with Enfortumab compared with standard chemotherapy like Docetaxel Paclitaxel or Vinflunine and that survival benefit was four months almost 13 months for
Enfortumab Vedotin almost nine months for standard chemotherapy that was the median survival and the hazard ratio was stable compared to the original analysis similarly the progression-free survival was improved and there was a suggestion of perhaps a tale on the curve that a small number of patients continued without progression and the median progression-free survival was no different than the primary analysis an improvement of about just under two months but and the response rate was also essentially the same 41 versus 18 and so we really see stability of the numbers from the original report and I think this is important to for clinicians who are using this drug to understand that these data have not changed dramatically with longer follow-up what I do think is interesting is that at the two-year mark there is an almost 10 percent improvement in landmark survival just under 30 for patients receiving in Enfortumab compared to just under 20 with chemotherapy and again not the best numbers that we would like to see but in fact the best numbers that we've ever seen to date in third-line therapy in advanced European cancer and so you know we're now seeing some patients doing well past two years even in the third line setting which is really I think impressive
Question - Common Questions from Your Colleagues?
So one of the most common questions is about toxicity from the clinical trial and use of Enfortumab and I think it's important to note that the safety profile has been stable after two years there were a few cases of rashes and and that were seen late but most of the events particularly the more serious rashes for which there's a black box warning occur within the first month of treatment I mean it's very important to be conscious of skin toxicity with Enfortumab Vedotin because there is a very small number of patients who can experience very severe skin reactions even like Stevens-Johnson's and TEN although I will say it's again a very small number of patients and early on in treatment being cognizant of skin reactions and risk and making friends with your dermatology colleagues is very helpful dose reductions and dose holds are also helpful and I think that that's a key point around this drug for physicians who are using it and may not have as much experience with it as of yet I see patients weekly during the first two cycles at a minimum I sometimes see them weekly even beyond the first two cycles in fact but certainly at the beginning it's worth seeing them every week and thinking doing a skin exam and asking for symptoms in order to understand whether patients have any skin toxicity and not being afraid to skip a dose hold the dose or reduce the dose if you start seeing problems and often these things get better with time and dose reduction but patients with mucosal involvement or blistering lesions probably should need more rapid evaluation by dermatology and are really at risk for serious complications and often shouldn't be resumed on treatment
Question - Will This Affect Clinicians Today?
The data that we have today I think will make physicians more comfortable with using Enfortumab Vedotin in this setting that it is a a very active drug in refractory patients who frequent who previously had no standard option and the fact that these that we now have data two years in on the trial with median follow-up over two years for patients is really reassuring that the drug is performing as we've seen in the past there aren't unusual late side effects that we did not know about before and so people can feel comfortable using it and that there are some patients who do do in fact do really really well with this agent
Question - What Are the Next Steps?
Enfortumab Vedotin is being tested in earlier lines of therapy in multiple clinical trials there is data that has been reported for the combination of Enfortumab and Pembrolizumab in untreated cisplatin and eligible metastatic patients these are first-line patients who can't receive cisplatin and the response rate in the in the phase 1b study of EV103 showed a response rate of 70 73% with a progression free survival and overall survival of about 12 and 20 more than 24 months respectively and these really represent a a very big improvement in compared to historical data and there are two randomized trials that are looking at this in the metastatic setting the first is EV103 cohort K comparing EV monotherapy to EV and Pembro with the idea that EV monotherapy we need to understand the contribution of UV monotherapy in this patient population and may lead to an accelerated approval in the united states for the combination depending on the results and we'll see that data I'm hoping within the next year the other is a randomized phase 3 trial comparing EV Pembro to chemotherapy in this first line metastatic urothelial cancer and this trials enrolling all comers randomizing to Gemcitabine and platinum either cisplatin or carboplatin or to EV Pembro and this would hopefully result in the full approval of the combination and perhaps replace chemotherapy in first line bladder cancer if it is positive there are also several trials ongoing looking at this as neoadjuvant therapy the combination of EV and Pembro and there's an ongoing study of EV monotherapy that's occurring patients in through EV103 an additional cohort on that clinical trial and so the development program for Enfortumab has taken some very interesting turns and i think this will be exciting to see the results of the of the combination studies that are going forward and we're going to see some more data on also pre-operative therapy in the coming years
Question – Final Thoughts
The data that we presented at ASCO 2022 is very compelling in terms of consistency with the primary data and consistency across trials and Enfortumab Vedotin has is one of the few drugs where the response rate in phase one phase two and phase three were essentially within a relatively small margin of error and we see tremendous activity in the first line setting in combination with EV Pembro so the future is is I think brighter for bladder cancer patients in general because of this drug although you know again mentioned must be made about the severe skin toxicities that that are sometimes seen early in the course of treatment and that can be limiting for certain patients and and even dangerous for very very very rare patients and so it is a drug that has a lot of promise and may move and transform early lines of therapy but the data that we have in third line for the long-term follow-up of this trial does show consistency across trials and including the long-term data with this trial