ESMO 2023 GU Cancer Highlights – SunRISE-1, EV-302, PSMAfore

Welcome to ESMO 2023 GU Cancer Highlights Hello everyone, I am Rahul Ghossein. And I'm Rohika Singh and we are oncology brothers. Even before annual ESMO 2023 meeting started, there was a lot of buzz around practice changing studies coming along in Gu oncology particularly with bladder cancer. There was a lot of data presented, but only one got standing ovation as a double the overall survival benefit. Today we'll focus on three key studies from ESMO 2023 and to go over this important data, we'd like to welcome Doctor Rayna McKay from UCSD. In our discussion. We'll start off with Sunrise one in non muscle invasive bladder cancer, then focus on EV3O2 for metastatic bladder cancer and then close with PSMA 4 and prostate cancer. Rayna, thank you so much for joining us. Speaker 2 That was my pleasure. Thank you for having me. Speaker 1 Rayna welcome. SunRISE-1: TAR-200 for BCG-Unresponsive Bladder Cancer To start, we picked out Sunrise 1A Phase 2B study because most of the patients with bladder cancer diagnosis present with non muscle invasive disease out of which 40 to 50% can in fact be BCG unresponsive. We have started seeing more and more of these patients in our practice as medical oncologists post approval of pembrolizumab in this space. Here in this study we looked at two different agents TAR 200 which is an intra vesicle delivery system giving chemotherapy locally versus cetralimab APD 1 antibody and complete responses with single agent TAR 200 are very impressive. Your thoughts here? Speaker 2 No, I mean I think this is an unmet need in bladder cancer for patients that have BCD refractory non muscle invasive disease. Right now the standard of care is largely moving forward with radical cystectomy in these individuals. And so you know developing treatment options that can help control the disease, prevent development of muscle invasiveness is really critical. So I think these data are very, you know, we certainly welcome such a high response rates in this setting. I think you know you know hopefully this is going to be something that's going to translate into you know clinically meaningful delays of radical cystectomy and and not you know compromising oncologic outcomes. You know, I think looking at the centrally assessed and investigator assessed, you know, CR rates particularly in individuals who have BCG refractory CISI mean that's a very high risk population for developing. Muscle invasive disease you know greater than 75% you know that's that's excellent. Speaker 3 You know their their numbers are are small but I think this is definitely signal finding and warrants further investigation in a larger study right now. Thank you for going over that. You brought up radical cystectomy. There was actually a clinical study that looked at patients preference being what are your options radical cystectomy versus any experimental arm and close to 90% of the patients said I would rather choose an experimental arm. And again the point being here is that the quality of life data and patient preferences to preserve that bladder and these results are very exciting because if not then our option like Roy had mentioned immunotherapy which has also not been a home run by any means. Speaker 2 Yeah, and I completely, completely agree. EV-302: Enfortumab Vedotin & Pembrolizumab in Urothelial Cancer So moving right along, in metastatic bladder cancer, the Cron standard of cure in first line settings has been chemotherapy followed by maintenance immunotherapy earlier this year. And fortumab with pembro was approved based on phase two study for CIS ineligible patients. This brings us to EV3O2A phase three study looking at and fortumab with pembro and CIS eligible and CIS ineligible settings versus standard of cure chemotherapy arm. The primary endpoint here was PFS and OS. Reyna, what did the study show? Speaker 2 This was a landmark study. I mean, slam you, you wait 30 years to see a study like this. I mean it was spectacular to see for our patients who have metastatic bladder cancer looking at overall survival that's approaching 3 years for this population. I mean, it is unheard of. What systemic therapy option in the metastatic setting is associated with complete responses? close to 30%. I mean, it was just astounding. I mean, being at ESMO, being in the room. Honestly, as soon as the OS curves were displayed on the screen, there was a. A standing ovation in the room because it was really a home run for patients. We actually witnessed the standard of care changing right there right before our eyes. I think no longer is it ethical to give any platinum based chemotherapy for frontline bladder and you know I think it I think this is a this is a win for patients. I think thinking about reducing this to practice a lot of questions are how can I use this sooner how can I use it. Earlier we saw data presented from. EV3O1 looking at neoadjuvant utilization of this regimen and you know even thinking about utilization across other tumor types that have high necked and expression I think is I mean this was a slam dunk. Speaker 1 It truly was, and I feel like now slam dunk home run boards don't even do justice looking at these overall survival curves. Now also we saw the data on Checkmate 9 O ONE with cisplatin, GEM Slider Bean, nivolumab. That combination data also has overall survival benefit. But here in US with EV and pembro being our new standard of care, any clinical pearls particularly for and fortumab in this setting? Clinical Pearls and Second-Line Sequencing for EV-302 You know I think just to step back and think, I think one of the issues with this study was thinking about post EV or utilization of immunotherapy in the maintenance setting in the control arm. But actually about 30% of patients received maintenance checkpoint inhibition. So I think it does reflect a real world patient population. I think EV is a very interesting agent that does require a specific. You know, focus on side effects. There can be some distinct side effects associated with EV as individuals start using this agent. In practice, given in the US, it's actually already FDA approved, things to watch out for include the dermatitis, the rash, the hyperglycemia, the peripheral neuropathy. So I do think that there's going to be a learning curve with utilization. And ensuring that patients have appropriate supportive care, there's appropriate dose modification as needed to ensure that patients can really, you know, maximize the benefit of this treatment. Speaker 3 Absolutely. This indeed is going to be our new standard of care. However, this poses some unique problems. What to do in second line as we do not have much data for chemo or even or defetinib after progression on IO and antibody drug conjugates. Reyna, what are you going to be doing in your practice? Speaker 2 So very interestingly in the in the treatment arm about 1/4 of patients went on to receive platinum based chemotherapy. And so I do think subset analysis from this study looking at the types of therapy that people received is going to be critically important. I don't think that this study results in removal of platinum from the treatment landscape for for bladder cancer platinums are are clearly very effective. And my suspicion is that that that may evolve into a second or third line setting to patient on the depending on the patient profile. But you know the EV arm, like I said, 1/4 of patients did receive second line or later line of platinum. PSMAfore: Lutetium PSMA in Castrate-Resistant Prostate Cancer Thanks for that. Now moving right along, taking the limelight away from bladder cancer for next few minutes, let us focus on PSMA 4 study in prostate cancer. In this study, Lutetium Plavito was looked at mainly for metastatic castration resistant prostate cancer patient population after they've progressed on first line androgen receptor pathway inhibitors and patients were rather chemo naive in this setting. Rayna, your thoughts on the study design and its findings. Speaker 2 So this was a very important study building off of the early data from the VISION trial. The VISION trial led to the introduction of Lutetium PSMA into clinical practice. That study was designed specifically for patients having received a prior taxing and having progressed on an ARSI, and patients were randomized to receive lutetium plus standard of care versus standard of care alone. And so at the prior to these these data we were largely utilizing you know Lutetium in the post taxing post RISIRSI setting. So this trial actually demonstrated that there is efficacy of Lutetium both pre and post chemotherapy. This trial doesn't really answer the question of what's the most appropriate sequence. But it does provide efficacy data on the utilization prior to chemo. The study was designed with crossover allowed in the ARPI control arm and 80% of patients approximately went on to receive LUTETIUM in the control arm, which is obviously going to affect that overall survival signal. But we saw pretty dramatic response rates with prolonged PFS. With this agent in the pre chemotherapy setting. Speaker 3 So I think you know the hope is that potentially the label for this agent could be expanded to especially include patients that have not received prior chemotherapy really to give patients more options as you're sequencing therapies in the MCRPC setting, absolutely. Utility of PSMA PET Scans in Prostate Cancer Staging This of course is a very active agent. I think that the bigger thing is accessibility. We really hope that this is going to be more accessible to more and more institutions for us to use this. Rayna, in your day-to-day practice, are you now using PSMA PET Scan for all your patients to be staged over other imaging modalities? Speaker 2 So, very good question I think in the context of MCRPC. The utility of Apsma PET is largely for eligibility for radio ligand therapy or potentially clinical trials. It is not for assessing disease progression or disease response. Those criteria to define progression and response with PSMA PET have just really not been defined. We don't really know what an increased SUV means in an existing lesion. Is that progression? We don't know. It's certainly being utilized for those patients that have newly diagnosed disease, particularly those individuals with high risk localized to assess for occult metastases. It's also being utilized in the biochemically recurrent setting to assess for you know algo metastatic disease. I would warn against use of PET imaging for. Speaker 3 Volume Assessment of disease in the MHSBC setting, you know these criteria for high and low volume have been largely defined based off of conventional imaging and not PSMA PET imaging, absolutely. Key Takeaways from ESMO 2023 GU Cancer Studies Those are such great points. Thank you so much Rena for going over these practice changing studies with us today. Post SMA 2023, we certainly have new standard of care treatment for bladder cancer. While the rest of the data is still evolving, do those who are listening stay with us for a short summary? As community oncologist it is exciting times to see so much happening all around us in this segment. We have covered three important studies in Gu oncology space post ESMO 2023 with doctor Rayna McKay, Sunrise one for TAR 200. Speaker 3 With such promising results and complete responses, this will hopefully fill a big unmet need, particularly in BCG, unresponsive non muscle, invasive bladder cancer patient population post asthma 2023 and fortimab vidotin. The pembrolizumab should be our new standard of care in first line metastatic bladder cancer as it has doubled the overall survival benefit in this patient population. Speaker 1 Lastly, we covered PSMA 4 study and the significant improvement in PFS with Lutitium PSMA in metastatic castration resistant prostate cancer patients. Make sure to check out our highlights on breast cancer, GI malignancies and lung cancer post ESMO 2023. And we are the oncology brothers.