Hi, good afternoon everyone. I'm Leslie Randall. I'm a GYN oncologist here in the United States. I'm the division director at Virginia Commonwealth University and I want to thank CGen and the GOG partners for sponsoring this symposium today and I also help with the clinical trial portfolio for GOG partners and we are so excited to have a cervical cancer symposium here for you today. I think we'll go through and introduce our esteemed panel. We have a really special treat for you all. This symposium is titled It Takes a Village because we have a village of people up here that represent different aspects of our discipline that help with the holistic care of our cervical cancer patients. So myself, you know me, I'm going to hand it over to my colleague, Dr. Solani. Good afternoon everyone. My name is Ruthie Solani. I'm at UCLA. I'm a gynecologic oncologist and it's truly a pleasure to be here and have a symposium dedicated to cervical cancer. Hi, my name is Megan Birkenstock. I'm from Johns Hopkins. I'm a humble ophthalmologist so I am happy to be here with you today to talk about the eye management of Tisodamab. Thank you for having me. Good afternoon everyone. My name is Sarah Hayward. I am the clinical pharmacy specialist at Stevenson Cancer Center at OU Health and here to talk about patient education and then a lot of the implementation of getting programs going to make sure your patients are treated safely and effectively. Hello everybody. My name is Chandra Hall. I am a 20 plus year cervix cancer survivor diagnosed at the tender age of 28 years old. I'm the Southwest Regional Director for the National Cervical Cancer Coalition and I also run a clinical research regulatory affairs division for an oncology division in Arizona. So thank you. Thank you everyone. So I think you can see that we're privileged here in the United States to already have access to Tisodamab for our patients and it really took a team effort to roll this out. We hadn't really launched a drug in GYN oncology before. Every drug that we've used in GYN oncology aside from maybe Distarlamab we already had on the shelf and that had been approved for other indications so this was the first time that we had to kind of do this ourselves and it really took a team and each member of that team is represented here today so I want to thank you all for joining me. I will serve as the moderator today and the learning objectives for this symposium are advancing this. There we go. The learning objectives are to increase provider knowledge related to clinical data for the FDA approval and newer therapies and advanced and recurrent cervical cancer. The current investigational agents that are under evaluation for early advanced and recurrence. Greater confidence related to selecting therapies and treatments for women with advanced and recurrent cervical cancer. Understanding appropriate biomarkers. Understanding antibody drug conjugates. Reducing treatment related side effects and issues in proactively managing those side effects. And we hope you gain greater confidence in the ability to counsel patients with cervical cancer on available therapies. Get the patient's perspective which is so important and discuss options with your pharmacist and your ophthalmologist. Thank you. So let's get started. Great and this is our agenda for today and I'm actually going to start with the landscape. So I think many of you are aware that a lot has been happening in the cervical cancer arena. And we've had two FDA approvals in the last year for cervical cancer here in the United States and I know that there have been some approvals in Canada and Brazil as well and we'll talk about those in the course of my talk. But things are really changing and forever and ever. We just and we had Bevacicimab in 2013 and after that we really just didn't have much going on in cervical cancer and it's as we all know a difficult disease to study because the patients who have cervical cancer often aren't in areas where we can get clinical trials to them. So progress has been slow but it's happening. This is the current treatment for cervical cancer. So we know for dysplasia we try to detect that at a pre-invasive stage and resect that. Same for early stage cervical cancer, we treat that with surgery and followed by adjuvant treatment based on any risk factors that patients may have. And then for locally advanced disease, we saw in the first opening plenary that the standard of care has not changed since 1999 and it didn't change with the presentation that was delivered yesterday, unfortunately. So we still have an immunotherapy trial in the front line pending and hopefully that one will be positive but that still remains to be seen. In the metastatic setting, platinum based chemotherapy has really been the mainstay of treatment and as I referenced the 2013 approval of Bevacicimab and then Pembrolizumab has really revolutionized the second line space and then that was the spark that sort of set off the development in cervical cancer. So this was keynote 158 where immunotherapy first came on to the sort of approval scene and this was a basket trial that included really all tumor types and there was an arm for cervical cancer patients and this was it was restricted to the common type squamous, adenosquamous and adenocarcinomas and what they learned in that study was that patients who were PD-L1 positive did respond to Pembrolizumab at about a 14.6% response rate but those responses, those patients had long duration of response. So if you did respond, you did very well. If you're a PD-L1 negative, there were no responses in that group. And so it appeared that this was a therapy that should be restricted to PD-L1 positive patients and that is in fact how it was approved for the second line or greater cervical cancer. And this concept, that was a single arm study, this concept was studied in a randomized fashion with another PD-1 inhibitor called Simiplimab and this was put against physician's choice chemotherapy with the primary end point of overall survival and Dr. Tewari presented this at ESMO last year and Dr. Hoaknin updated this analysis at ESMO this year and showed that Simiplimab significantly improved overall survival versus chemotherapy in the second and third line setting. So it was a phase three sort of confirmation of the concept that immune therapy worked in this setting. And if you look at this data, PD-L1 status didn't matter. Now they measured PD-L1 in a different way than was measured for Pembrolizumab and so that probably matters, the way in which you measure the PD-L1. You can't draw conclusions based on this data whether that played a role in showing no difference between PD-L1 positive and negative patients. So this was put forth to the FDA and was not approved in the United States. It's complicated most likely because we already had Pembrolizumab and there might not have been an urgency for another therapy in this space and I think there was confusion at the time about the PD-L1 status but this is now approved in Canada and Brazil. But interestingly, I've talked to my friends in Canada, even though they have this approval, it takes about a year for it to actually reach patients in Canada after the approvals and I'm not sure what the status is in Brazil. I know for Tisodimab, for Pembrolizumab, as soon as those were approved, we were using those in the clinic pretty soon thereafter. So a year to wait for a drug for patients who need it is a pretty significantly long time. So we don't have a lot of studies in GYN oncology that show an improved quality of life with a new agent but this is one of those trials. Simplumab did improve quality of life over physician's choice chemotherapy. Most of our studies show no detriment in quality of life and in most cases you'll have equivalent quality of life between an investigational agent and the standard but here there was a clear improvement in quality of life and I want you to remember this slide in just a moment. So the confirmatory trial for the Pembrolizumab approval was actually to move it up into an earlier line of therapy and that's what the Keynote 826 study did. So this was moving Pembrolizumab in addition to the GOG 240 regimen and we know that a lot of patients have contraindications to Bevacizumab and so this trial allowed for physician's choice Bevacizumab in that regimen and this was for persistent recurrent metastatic cervical cancer that is basically would be a candidate for the GOG 240 regimen. They couldn't have had prior systemic chemotherapy. They were stratified by metastatic disease at diagnosis, PD-L1 positivity and the CPS score and whether they were planned for Bevacizumab use or not. They were randomized one-to-one. The primary endpoints were a dual primary endpoint of both overall survival and progression free survival and this was the results for the progression free survival. It was significantly improved. The hazard ratio of .62 for the PD-L1 positive group and for the intent to treat which included the PD-L1 negative group was also statistically significant. Interestingly, 90% of the patients were PD-L1 positive and so before this study we thought the positivity rate was about, I don't know, what did we say, 80? Yeah, 50-60%. We talk about this all the time. It was about 50-60% but we realized in this study that it was much, much higher and when you look at the subgroups, the hazard ratio for progression for the PD-L1 negative group was one and so in the United States, the FDA only approved this for PD-L1 positive patients even though that small subgroup was not powered to draw the conclusion that it was not active in the PD-L1 negative subset. So we had this restricted to PD-L1 negative but this just got approved and I wish I could remember which country it was. It just got approved in another country for PD-L1 agnostic. So it's really sort of interesting how this PD-L1 story is playing out. I think it is a predictive biomarker, there's no question. However, it's not a perfect biomarker and we have, it's so ubiquitously positive that drawing conclusions better trying to study it is a little bit difficult. So this is the PFS and OS in the all comers population. Again, the PFS significantly improved and then the OS an improvement in survival as well. So you remember the GOG240 improvement in survival and now we've got an increment better for overall survival. And in fact, Dr. Tiwari who's done a lot of this work in this space published a review that showed kind of how far we've come from cisplatin alone where we couldn't even get patients a year out from their diagnosis. Really, cisplatin paclitaxel was the first time we broke that 12-month mark and Bevacistamab added another five months of survival to that. So here's where Keynote 826 takes us. So to me, I mean, I see this slide all the time and it gives me chills every time I put that up because if a patient walks into my office with stage four cervical cancer and she's PD-L1 positive, it's not unreasonable that her median overall survival could be 24 months. Now that doesn't apply to an individual patient, but to me, that was never possible when I was five years ago. That was just not something that we ever hoped for with a very acceptable safety profile. I will say that about 60% of patients in the 826 study did get Bevacistamab and in the sub-analysis, they did better if they had Bevacistamab, but there was still a benefit if they did not receive Bevacistamab. Again, so Simplamab showed improved quality of life and so did Pembrolizumab in the front line. So again, we have two trials, which is a rarity to show an improvement in quality of life in GYN cancer, but we've shown that twice now with immune therapy and cervical cancer. So this is a very consistent theme. So this is a very important therapy for our patients. So there are combinations of immune checkpoint inhibitors that are in the pipeline. We've got Nivolumab combined with Ipilimumab and the Checkmate 358. You can increase the response rates, especially in the PD-L1 negative population by adding CTLA-4 inhibition. We also have a combination, Valstilumab, Zalfrelumab, that's been presented and you can see the response rates there. AK-104, ooh, I need to update that. That has been approved in China. It is PD-L1 agnostic. It's an improved response if you're PD-L1 positive, nearing 60%, but about 36% if you're PD-L1 negative. So that's a very active therapy. Ventrafuse-alpha was a combination with a TGF-beta. That may not go forward. We have Teregolumab, Atezolizumab that Dr. Solani is studying in the Skyscraper 4 trial that we're awaiting those results, and we have Tisodamabidotin in addition to Pembrolizumab, which shows a very high response rate independent of PD-L1 positivity. So these are really interesting things coming down the pike. So this is how treatment paradigm is evolving for metastatic disease. It's based on PD-L1 positivity. It's the keynote 826 regimen. For PD-L1 negative, GOG240 remains the standard of care. In recurrent disease, no prior checkpoint. You're going to Pembrolizumab or Simiplumab where it's available, and if patients have had prior checkpoint, really we have one key player in that space currently, and that's Tisodamabidotin, and if you don't have access to that, then it's other chemotherapies, which, you know, unfortunately are marginally active, and the response rate of chemotherapy in the Simiplumab trial was 6%, so not great, and you saw the PFS curves in the control arm for that trial. So this is Tisodamabidotin. It's an antibody drug conjugate that targets tissue factor. It's conjugated to a monomethyl R-statin E, which is a microtubule poison, so it's somewhat like a taxame, but not exactly. Each molecule has four drug moieties attached to it, so it's a high drug concentration, and the point is to take the drug into the cancer cell, basically where it belongs and where it needs to be. So most cervical cancer expresses tissue factor. That's over 90% expression, so we don't do tissue factor testing, and it's not required, and this drug is approved for any tissue factor expressing. In fact, you can get an assay to check that. It's only investigational. So when the drug goes into the cell, the drug is endocytosed. The drug's released. It has its own cytotoxic effect, and then the cell dies, and then there's bystander effect from the soluble drug in the tumor microenvironment, and it also induces an antibody-dependent phagocytosis, which is almost like an immune response, which is very interesting. So this works in multiple ways. This is the study that got accelerated approval in the United States, the GOG3024 and GOT-CX Inova TV204. Single-arm study, again, for accelerated approval. This is the second and third line cervical cancer. 101 patients were treated with tesotamabidotin. This is the starting dose, 2 mg per kg. IV every three weeks. They were treated until progression or unacceptable toxicity, and the primary endpoint was objective response rate by resist, and you can see the other secondary endpoints here. And these were the results. So we had seven complete responses, second and third line cervical cancer. These are chemo-progressions. So just think about these patients that you take care of, what this means for them to see seven complete responses, 17 partial responses. So the overall response rate was 24%, but if you look at the stable disease, that was 50%, so the disease control rate is really approaching 75% here. And importantly, the median duration of response was 8.3 months. So it's not enough just to respond. That response needs to be durable, and in this case it was. So interestingly, and this is why we have a whole panel here today, ocular toxicity comes along with this drug, and it was really sort of a kind of a dreaded potential complication. Most of the adverse events seen in the trial were grade one or two, or really just grade one, and mostly grade one, and we've learned over the programmatic development of this drug ways of mitigating and preventing that, and we're going to talk about those today. Tissue factors and the coagulation cascade, so bleeding can be a side effect. Again, this is mostly grade one. Peripheral neuropathy, because of the MMAE, it's not a taxane-like neuropathy. It's a motor sensory neuropathy, so it presents often as weakness. So it's an interesting side effect there. But patients who have grade two neuropathy should not go on this medication, and I wouldn't say in my practice that persistent neuropathy from prior therapy is really much of an issue. So these results led to the approval of Tizotimab in the United States. This was back in September of last year, so I guess we're on the anniversary of this approval, which is really exciting. And this is the confirmatory trial for that that's ongoing. This was open in the U.S. It closed when we had commercial availability of the drug. This is now continuing in the rest of the world. It's open in Europe and Asia and other countries, and it's the Tizotimab-vidotin versus investigator's choice chemotherapy. So it's very almost identical design to the Simiplimab trial, and the primary endpoint here is overall survival. So this trial is ongoing. So thank you for your attention. I'll turn it over to Dr. Slavany. Thank you. So we thought it would be fun to just kind of go through a case. We're going to have some audience response questions as well, and we really welcome – there's microphones throughout the room, so really welcome comments or questions. We have a great panel here to kind of review different things. So I just wanted to start with a case presentation of something that we commonly see with cervical cancer. So as we know, the median age is pretty young in these patients, so 46-year-old with stage 3C1 squamous cell cervical cancer who received chemo radiation with cisplatin and brachytherapy, which she completed in February 2019. So then in January 2021, she presents to you. She has a cough, and her scan confirms a pulmonary lesion, which is then biopsied, and confirms recurrent squamous cell carcinoma with a CPS of 5. We didn't talk about biomarkers, but if there's questions, we can definitely discuss that as well. So now with the new Keno A26 indication, she receives six cycles of carboplatinum, paclitaxel, bevacizumab, and pembrolizumab with a partial response, and continues on with maintenance bevacizumab and pembrolizumab as per the protocol. She's been on maintenance therapy for a year, but she knows return of her cough, and she undergoes additional imaging, and her scan now reveals progression of disease with pelvic lymphadenopathy and increasing size of pulmonary metastasis. So we wanted to kind of discuss treatment options. This is not the correct question. It is. Okay. Oh, wait. Go back. Let me go back. Sorry. Okay. That's it. Yeah. Okay. I don't know if there's a poll option here, but we just figured we'd think about treatment options. So things to consider, you know. So this patient's received PembroBev now for maintenance for a year. Would you consider adding a CTLA-4 inhibitor to her maintenance regimen that she's on? Would you change her to Tisodamab-Vidotin? Would you change her to platinum-based chemotherapy? It's been a year since she's been off. Or would you consider a non-platinum-based chemotherapy regimen? So if you could put in... How did they vote? They did a QR code in the beginning. Perfect. Yeah. Can you go back to the results? Great. All right. So I think there's not really a wrong answer here. So all of these, and we're going to talk about Tisodamab-Vidotin because I think this is what's kind of becoming the now contemporary standard of care for these options. We don't have data on CTLA-4 inhibition adding to this at this time, but I think it's something that's compelling and I think combination immunotherapy will be explored more. And I'm actually kind of glad that nobody picked chemotherapy. We know this is toxic. We know there's a lot of side effects and quality of life issues as Dr. Randall demonstrated in her presentation. So excited to talk to you a little bit more about this regimen in more detail. I'm going to insert a poll question that you'll just have to do the old-fashioned raise your hand. How many of you picked Tisodamab-Vidotin and you have access to it? How many picked Tisodamab and you don't have access to it yet, but you would use it if you did? Great. Great. Great. Thanks. Okay. So we are fortunate to have a patient advocate with us as well, but what treatments do you think patients have the most concern over treatment side effects? So think about it from a patient's standpoint. Platinum-based chemotherapy, Bevacizumab, Pembrolizumab, or Tisodamab-Vidotin. And obviously, we talked about this a little bit. Chandra, I love your input, but how your counseling influences this as well. All right. And so I think this is a... I'll let you guys answer a little bit more. And so definitely, definitely a lot more on chemotherapy, but Tisodamab-Vidotin, Bevacizumab, not so much for Pembrolizumab, and I think that's some of our familiarity with this agent as well. Before we move on, Chandra, I know we've talked about this a little bit, but I'd love to hear your input. So from a patient's perspective, this question actually is a little misleading. It's based on the assumption that you've got a very sophisticated, clinically educated patient. The answer from the patient's perspective is, give me where I want, something that's not going to make me feel so sick, what is going to be my quality of life, and what's going to give me extended life, and have that quality while I have it. And so when you discuss treatment options with your patients, keep in mind, that's what's going through their head. They don't want to die, they don't want to be so sick they want to die, and they want to live as long as they can. So based on that, that's what I would just ask that you keep in mind while you're talking to your patients and presenting these options to them. Thank you. Yeah, thank you. And I think that's super insightful because I think we do review response rates with patients and putting it in context, and I think one of the other key things is how do we mitigate these side effects so that patients do have an optimal quality of life, which we're going to have our panel speak about a little bit further. Did I skip a question? Okay, and if efficacy were equal, what do you think a patient's choice would be adding a CTLA-4 inhibitor to regimen to sodamabidotin, platinum-based chemotherapy, and non- or non-platinum-based chemotherapy based on your experience of toxicity? All right, so it looks like a majority, as answers are still coming in, looks like about half of the group would say to sodamabidotin, and I think, you know, if efficacy were equal, I think this does become a little bit more nuanced, so I think this is a very interesting question here and responses. Can I ask Shonda a question real quick? Do it. Yeah, what do you think about, I mean, so can you go back to that result? I just want to ask you about, so this eye toxicity to sodamabidotin, like, from a patient perspective, you know, how scary is that to hear, that it might affect your eyes? You know? Quite, but knowing, so the general consensus is that they know that there's going to be some toxicity on some level, it's just assumed when you're diagnosed with cancer especially. However, the messaging regarding eye toxicity, we're aware of this, we're going to manage this, it's important that you partner with me to make sure that we stay on top of this. And again, you've got to leave that decision to the patient, you've got to present them with all the options, all the risk benefits, and then let them make that decision. But, you know, not to get too graphic, if I'm going to have some eye toxicity, but it's going to let me watch my kids get another birthday or have another holiday, start school, I get another anniversary with my husband, and the eye toxicity is manageable, especially since we're going to do it together, then I would take that chance. Yeah, and it, go ahead, yeah. I was just going to say, it really also making sure that the patient has just reasonable expectations of something like that, it's making sure that you're not scaring them too much, but yes, we know this is a risk, but this is the percentage and this is what we really see, and this is how we're going to support you through the process and follow up and check on you and make sure that we're doing all of these supportive care agents so that you have the most successful, hopefully, and at least safe treatment through this therapy. Yeah, and I just want to add to that, I think that's exactly right, and I think partnering with our pharmacists, we've, you know, we have Epics, we have Beacon as our chemotherapy plan, and we have like these hard stops in there that we check and make sure the cooling packs are placed, and, you know, all these measures are done, which you're going to hear a little bit more about, and I think talking to the patient and just, you know, making sure the mitigation plan for the eye toxicity is in place, they understand it, because we want to keep you on a therapy that's going to work, and one of the most heartbreaking things is stopping a therapy that's working because of a toxicity, and so ways that in making sure that the patient's bought into this and is committed and that our team is committed to dealing with these issues is really key. It's new, though, right, like for some of us in the room. I remember when we first got Doxil, and I laugh because Leslie and I were sort of fellowship at the same year, 2005. Survival for cervical cancer was median of nine months, so, you know, it's really exciting to see that slide, but it just reminds us how much more we have to do, but when we had Doxil, we had this new skin toxicity, and I remember we were kind of a little bit up in arms about it, like it's so new for us, but, man, it's so manageable, right, and I think with the proper counseling, this is really something we can overcome. I mean, some of you may remember when we gave Taxol in an intensive care unit because of the hypersensitivity, and now, you know, that's just, you can't imagine that now, so we just evolve as we learn to manage toxicity. I think, you know, you all are exactly right, like you have to qualify. You can't just say, oh, this has eye toxicity and then end it there, like that, if you end the discussion there, then that's just, you know, that does incite fear and anxiety. You have to qualify it, so most of it's low grade. It's preventable. It's reversible. It's, we can detect it easily, monitoring, and we're going to get into Dr. Birkenstock's talk, and I hope we don't, like, interrupt you too much on that, but I think this is what a lot of people are really interested in learning. I will say, you know, because we're going to talk about eye toxicity a lot in just a second, I will say that, you know, the neuropathy for me is like the more difficult toxicity with sodium avodotin, and a patient doesn't, like, anticipate that one. They get more scared of the ocular, but in terms of, you know, what they think the patient's choice would be, I think the ocular might drive their decision a little bit more than what drives my decision, which is more of the neuropathy. So, just a quick anecdotal story. So, I've been in oncology in various forms for over 20 years as a patient advocate. I'm not clinical. The science freaks me out, but I'm doing the best I can to learn it, and I have so much love for all of you in this room because you're trying to save the lives of women like me. But let it be said, I had a colleague who always said, if they ever got cancer, they would never get chemo, they would never get radiation, they would never go through treatment because it's so very toxic. Guess what? They got cancer. And her husband told me that if somebody took a plate of human waste to her and said, this will give you another day of life, she would eat that every day. So, it's very, very heartbreaking for the patient when they're presented with all of these options. They're trying to navigate all of this when they're newly diagnosed. What am I going to do? How am I going to do it? Who's going to take care of my family? You know, the women in a lot of cultures are the hub of the hub and spoke model of the family. When that hub is broken, that family breaks down. So, the eye toxicity is something that you can easily partner with and communicate. And same with the neuropathy. Just, you've got to just be honest with them, set up realistic expectations. Don't freak them out. But your partnership with that patient is going to help them navigate all of that more than you would ever know. So, thank you. Thank you. That's actually very empowering to hear as a doctor because we get so freaked out. Like, we don't want anything bad to happen, you know. You know, we don't want our patients to have these toxicities. We don't like it. But that's actually very empowering. Thank you. All right. Okay. Thank you. So, we have another case. And so, just a little bit of different spin but kind of same concept. This is a 37-year-old with adenocarcinoma in April of 2021. She had a 2-centimeter tumor, negative imaging. She undergoes surgery. Final stage is a 1B1. She now, it's now two years later, August, or one year later, excuse me, August 2022. She presents with abdominal pain and she now has pelvic lymphadenopathy and peritoneal nodules consistent with recurrent disease. Her original tumor is tested and is PD-L1 negative. So, she's given six cycles of cisplatin, paclitaxel, and bevacizumab. And a CT scan is performed to assess treatment response and reveals disease progression. So, at this time, what would be your treatment options? Tisodamab, idodine, pembrolizumab, or simplumab, non-platinum-based chemotherapy, or nivolumab and ipilimumab? Oh, do I have to? Sorry. I might have advanced that too much. Yeah. And please keep responding. But just to talk while answers are still coming in. I think this is exactly right. I think there are some places where pembrolizumab or simplumab has approval in these patients. We always question the accuracy of the biomarker. So, I think we still need to explore more. Tisodamab, idodine has the indication here in the United States. It does not matter on your PD-L1 expression. And as Randall mentioned, you don't have to test for tissue factor because it's ubiquitously expressed. Before I move on, I just want to highlight one thing and compliment your talk is that the patients who went on tisodamab, idodine, about 54% of them had progressed on their most recent line of therapy. So, this was kind of high risk, high prognostic group. And there was a 24% response rate. You heard it was about 14% in PD-L1 positive patients with pembrolizumab in the recurrent space and 6% with chemotherapy. So, we have yet to see how this really impacts our survival outcomes. But I think this is really promising. And I think what we have to do is really work hard to get comfortable using this, get our patients comfortable with, you know, taking this medication or receiving this medication. And this is where our colleagues come in. So, with that, I will pass it on. Yeah, that's great. I do want to add one quick thing about those treatment options. Right now, tisodamab and Pembro or Simipumab, well first of all, so for the U.S., we don't have an IO option in the front line space for patients who haven't had, or the second line space for patients who haven't had prior. At the bottom of the pipeline chart, I showed you the combination of TV and Pembro. And I went through it really quickly, so you may not have noticed. It is a 38% response rate. And those are very durable responses. So, in a patient where I have an opportunity, and right now these are my PDL1 positive patients who haven't had checkpoint in the front line because it wasn't available when they had their front line therapy. I'm giving the combination. The, you know, the FDA label doesn't say that you can't. So, I have given the combination. And in fact, almost all of my patients on tisodamab or don't right now are on the combo with Pembro. You could do that potentially with Simipumab in places where it's available. I think that's an approach that's hard to get access to, but it does, it can work. And the reason I bring it up is because it's, if giving IO, the sooner the better is probably when it will work the best. So, if you, but you can also use the tisodamab. You could also sequence it and save it, you know, save it for later sort of approach. But saving drugs for later in cervical cancer is sort of a difficult concept. It's not like ovarian cancer that has a long post-progression survival. So, in order to get the best long-term, I tell my patients, Shonda, I tell them we're going to play the long game here. We're going to like try to get the most mileage out of each treatment that we can possible. And I think possibly combining that, and I don't know that for sure, and I tell them that, but it looks to me like giving that combo will give them the most time without the trade-off of toxics, with manageable side effects, yeah. I think another really cool thing, this was presented at ASCO this year, is longer-term data with a combination. Your median, I think 14 months follow-up had not even been reached. And we're talking about a median duration of response with single-agent, eight months for Tisotamab. So, I really do think the combination is going to be very powerful, but it's not quite mature yet. So, stay tuned, but I think that is going to impact us. How patients who've received prior IO therapy will influence that, I think, is yet to be determined. There were a couple of patients who did receive prior IO on that combination, but it's only about 30 patients. So, stay tuned. Great. Dr. Birkenstock. Okay. We can't wait to hear from you. This is what everyone, who's excited to hear about ocular toxicity with Tisotamab? Thank you. Oh, you make me feel so welcome. I love this. Thank you. And if you have questions, please, there's microphones everywhere. I will take any questions about this. I'm going to just start with a case and do a little basic review of the eye. 56-year-old female with metastatic cervical cancer had grade one and two keratitis during treatment. They were seen by an outside provider, normal baseline ophthalmic exam, and required eye care plan was followed to a T, received nine cycles of Tisotamab, four full, five reduced doses. After cycle three, patient presented to the oncology clinic for an unscheduled visit due to red eyes, and on the same day, we were consulted because we have same-day availability for patients, and when they came in, you can see how the cornea, and I don't have a laser pointer, but the cornea looks a little irregular, and that is the external surface, which is in front of the anterior chamber, in front of the iris, in front of the lens, and you can see it has almost like a pitted orange surface to it, and that's what we call keratitis, or superficial punctate keratitis, because it looks like little dots, and so we started steroid eye drops, and we'll talk more about the different varieties that you can use in addition to artificial tears for extra lubrication, and the patient, again, experienced red eyes five days later. We reassessed. We said, oh, it's grade two keratitis. There's a, not confluent, but there's still these punctate areas on the surface, and then repeat with the lubricating drops, and in a week later, it had decreased to grade one, and even though the tesotomab was, again, reduced, they were able to complete their treatment regimen. So how do we deal with this? We know it exists. We know it happens in a significant portion of patients treated. We do our baseline eye exam, and then we do one every three weeks before each infusion. We really advocate for no contact lens use, simply because we want to avoid any infections associated with contact lens use and or increased surface dryness. Prophylactic steroid eye drops should be given prior to starting the infusion to be continued 72 hours after the infusion, and then also the same time vasoconstrictor eye drops are given prior to the infusion, along with the cold packs, and this allows for a decreased blood flow to the ocular surface, whether it be the cornea or the conjunctiva, which are the outer layers of the epithelium on the eye, and we have a variety of drops, including your everyday Visine or Bermonidine, and finally, lubricating eye drops are key, and they're used both prophylactically and throughout treatment in order to relieve dry eye and overall irritation, and for self-use by the patient at home. So this is a nice three-pronged approach of how we deal with the eyes. First is make friends with your local ophthalmologist. You're going to need them. We are around, and we are happy to help, and one thing that we do, or at least I do in my own practice, is when I get a patient, no doubt they are scared, they are afraid of going blind, and I just assure them, look, we have all these points in place. We use the eye drops. They're ready for use. You will get the cooling packs. These are all standard regimens, and not only that, but I will be there for you. I'm not going to abandon you. It is rare to go blind with this. I can treat you. You call me, and we have an after-hours phone number. Rare. It never. Yes. Has anyone gone blind? There's a corneal perforation. Right, one corneal perforation, yes, exactly, so very, very rare, so I never say never, but I always say rare, and that helps alleviate some of the anxiety here, and also know that we can do dose modifications if necessary, and how do we monitor? So obviously, we want to know, as the ophthalmic professionals, if there are any dose changes. How is the patient doing systemically? As ophthalmologists, we are MDs. We still want to know how they are systemically. We repeat our slit-lamp exams, like I said, every three weeks, and after referral, oncologists on your end can help remind the patient, make sure they come and see us, because sometimes you can have toxicities associated with the treatment, i.e. steroid drops in long-term use can cause increased intraocular pressure leading to glaucoma and or cataract progression. Ocular adverse events are primarily confined to the ocular surface, whether it's the bulbar conjunctiva, which is the conjunctiva on the surface of the eye, and also the palpebral conjunctiva underneath the lids and or the cornea itself. And again, as I think was already mentioned, the majority resolve in a relatively short period of time. And then finally, if you don't have a friend in the ophthalmic community near you, you can also look at the Tosodamab dosing instructions. There is a link to WebMD where you can type in your zip code and you can find local eye care professionals. I also have a list of resources here if you're looking for general ophthalmologists and or cataract and refractive surgeons. It may be hard to find an ophthalmologist in your area, so if you have a trusted optometrist or other eye care professional that you trust, that might also be another ally. And when do I stop? When is it really getting rough? Well, we always refer to the current prescribing information, and the hard stops here from at least my end of the world are if simplefron, which is when the eyelids abnormally adhere to the eye itself, and or ulcerative keratitis, which can eventually lead to corneal perforation requiring transplantation. And those are the hard stops for discontinuation. The median time to onset of the first corneal disorder is usually between the second and third infusion, and then resolution is around a month. And so the oncology team should add to the review of systems. Are you having blurred vision? Are you light sensitive? How about eye redness or dryness or simply irritation? And all those should prompt referrals back to ophthalmology to make sure that there's nothing that could be treated early on that could progress to something more later. And finally, close communication, i.e., friends with your ophthalmologist, and make sure that we are doing you our service. Some of us may not be familiar with CTCAE and grading criteria, and we might just need a little nudge from medical school and also the newest literature of how to do this. But if you let us know, we can easily tell you the ophthalmic side of things, and then together collectively grade appropriately. Okay. I'm going to shake things up a little bit. We have a lot of time. Okay. Okay, great. On time. Thank you. Oh. You're welcome. Excellent presentation. Sorry. I'm excited to talk about this. So can we go back through her slides in the back? Can we just go to her? Because we're just going to pick this situation apart. Oh, I love it. Please. Please. Yeah. Go all the way back to the beginning there. Okay. And then go advance two more. Oh, I'm sorry. Go forward. Oh, that's right. Oh, thanks. I got it. I got it. Now you're in control. Yeah, yeah. I'm in control. Oh, I'm never in control. Okay, great. So first of all, I mean, make good friends with your ophthalmologist. Well, I'm great friends with my ophthalmologist, but they can't get my patients in. And I'm putting patients on treatment faster than they can see them, and they can't see them every three weeks. And when I say I need you to see them every three weeks, they look at me like I'm completely insane. So I mean, I think, you know, for us, we really had to rely on optometrists, and we've had to make it to where, you know, we're not going to know. We have patients coming in from all over a couple, you know, two, three hours away. They need to get these eye exams done closer to home. Like they're not going to come to our center ahead of time in time enough to have their eye exam completed by the time they get their infusion. So for us, it's been like we haven't had that upper, you know, that access. And I'm a little jealous of our colleagues at Hopkins who do have you on their team. I think our ophthalmologists would love to be on our team. They just don't have the bandwidth to do that. And so what we've done, and I think this is important if you don't have access to, you know, every three-week ophthalmology. And you may think this, and I want to hear your opinion, I want to hear from the patient's perspective and Dr. Hayward's perspective is operational implementation as well. Like, you know, if you don't have access, like how acceptable is it to use that optometrist and basically give them a paper that says they need a slit lamp exam and visual acuity and these are surface toxicities and this is what we're looking for. I mean, that's how we have had to do it and we've had good success with that model and then refer to ophthalmology when we find anything abnormal. So I'm just interested in others' experiences too. Well, I'm a little partial, but I think it's who you can partner with, right? I mean, if you have only one provider and it's optometry in an area, then you have to rely on who's close by. And I think getting the exam is very important, especially if you're laying out what toxicities you're looking for. Ideally, if there is any kind of increased grade or question on the grade, then you should involve your ophthalmic colleagues. So like I said, the main difference is as ophthalmologists, we are MDs, we went to medical school with you. We just do eye surgery for a living, different fundus, but we do take care of all kinds of emergencies including this and I would say this is an urgent thing. And so one thing to have the conversation, even if you haven't made friends with the ophthalmologist yet, is that these patients have a very complicated medical history. They're on a immunotherapy. This is what I'm looking for. Can you please help them? And I think most ophthalmologists, even though we see anywhere between 30 to 60 patients a day, if you're very concerned about something and you understand medically because you're telling us exactly what you're looking for, we can do a targeted exam for you. So I think it's location, location, location, and then trying to open up that door to availability. Great. Let's go down the line. Yeah. Sure. Yeah, I just want to echo exactly what you guys have spoken to already is just making that connection, that professional connection. Luckily, at our institution, we do have an eye institution on our campus that we've been able to partner with. But also, I'm from Oklahoma. We have a lot of very rural patients just like you who drive in two to three hours and trying to coordinate all that care to make sure that they get to see in the same day that we see them. And that's not always an option for them, for whatever reason or resources for them to come in and come to your fancy eye institute. And so what we did is we created our own paper-based form that we could send with the patient or fax or whatever it is and just some educational background and material like this is. And usually, we've been, and I apologize if I'm going to the optometrist because of accessibility. We can get in to see them rather quickly. This is what we need. This is why we need it. Can you please provide this information XYZ and fax it back to this number in a timely fashion so that we know we can make a proper decision in being able to treat the patient? And that's even what we've had to do because our eye institute, we don't share the same electronic medical record. So we just can't pop in there and see what their note said from that day or the day before. So that's how we've gone about it and just also having a lot of follow-up. Part of your team or nurse navigators, your nursing staff, your pharmacy staff, your infusion staff making sure that all those pieces are in place before you treat the patient. So me being from Arizona, we've got a lot of reservation land. My heart is also with a lot of the rural communities and, you know, they are way out there in the middle of nowhere in many instances. And so when they come in and they present, a lot of times it's with advanced disease and of course you as a clinician are thinking, okay, this is great, I've got to partner with this, I've got to partner with that. We've had good success using the marketing department. We've had our marketing department go out and try and make these relationships, especially with these particular instances where we have certain particular needs of a trial. Also nurse navigators, if you don't use nurse navigators, they are a beautiful complement to in the clinical setting because they're going to help get that patient, they're going to help with that relationship, they're going to find out where that patient is and then hopefully find, you know, an ophthalmologist. We're following. Thank you. They're going to help you find an eye doctor that can help you with this circumstance. So, you know, you're all amazing people and clinicians and you're used to being creative and so these are just some of the suggestions, you know, use your team, use your marketing department, use your nurse navigators to help you build those bridges so that your patients can get the care that they need from these other amazing specialists as well. I think navigation is key and it's a really important point. How many of you have access to navigators? Just a show of hands in your instances, put them up high, yeah, don't be shy, yeah, okay. So not a lot and, you know, we're really, I guess, you know, we're spoiled, we have navigation, I can't imagine functioning without navigators and so, you know, that's a very small portion of this audience that has access to navigation, yeah, okay, well, I'm privileged and grateful. Great. Okay, let's talk about contact lenses. How big of a deal is it, you know, to the patients not to be able to wear their contact lenses during? About a quarter of my practice is dry eyes and one of the main culprits is contact lenses and so it really helps and I get it if you are a high prescription and your glasses look like Coke bottles, you love your contacts, it gives you your peripheral vision back, you see so much better but at the same time, it's just another key that if you're going to wear them, you really have to use the artificial tears a lot and it's a risk-benefit discussion, you know, maybe wear them every once in a while, just not every day. Dr. Hayward, what about your patients, do they, their contacts, a problem? That has never been a concern, honestly, we had a patient turn down the therapy because the eye drops, quote, creeped them out and they couldn't do that. That would be me, if this happened to me, I would really have a hard time, I hate eye drops. Phobia, I suppose, is what it was but that's not something that I've run into that anyone has immediate concern with, they just go, okay, but it's also just, and along the lines with the eye drops themselves is accessibility. There's lots of different versions and I'll let Dr. Birkenstock kind of speak a little bit more of this but, you know, what is it you have on formula, what's cheap, what's available? Yeah. The question is, is the oncologist going to prescribe it, is your ophthalmologist going to prescribe these, at our institution, we just kept it with the oncologist so we had a bit more control and knowledge of knowing where it was sent. We have a specialty pharmacy as well, which we're very lucky to have, that we're able to connect those patients with that pharmacy to get those products, but just know that you have those different options. They even have a text service available that can help remind patients when it's time to take their drops, if they're the forgetful type person, and then really kind of, while on that subject, preservative free eye drops, and you can touch on this a bit more, but that's really the key point. The only thing is you have, they're a bit more expensive, they're little individual droppers and so they're not quite as handy to tote around all the time when you're expected to put them in your eye at least four times a day. And so just making sure you have access to that, being able to give them examples of what that means as opposed to having one that doesn't say, but it has to say preservative free. See, all the things you're saying are just an example of why we need this team to manage these newer therapies, and it's not just to SodaMab, you know, this is just, will be one of many. But, you know, we didn't really have, we had PharmD that was part of our team, but really got fully engaged with our, you know, our trials program and our TB program. And we couldn't run, you know, we could not have implemented it as quickly without her. It really sped up our startup process by months to have our PharmD. And honestly, you know, I think as GYN oncologists, realistically, if we continue to operate and give chemotherapy, like that, with all these new treatments coming around, like how are we going to keep up with all of the safety and the toxicity management without partnering in that way? So that's interesting. I was going to ask you about the eye drops next, so you read my mind. That's great. Yeah. Chandra, what do you think about, you know, patients like, I can't use my contacts, I have to do these eye drops, like what is that like from a patient's perspective? I think it's a non-issue. You know, they're dealing with, seriously, I think that they're dealing with a really serious illness. And if those eye drops are going to give me my sight, let me keep my sight. If they're going to help me get better, I'm going to do whatever I can do to stay compliant. Women seem to be a little bit more compliant than men when it comes to treatment. I found anecdotally across the board, I don't know if you found that as well, but I really don't think that that's going to be. No, no reference. We don't treat. We only have one. No men. No boys. We have no frame of reference. Yeah. I see it both ways. But in any case, yeah, I don't think it would be problematic. I think maybe after a while, if it becomes inconvenient, they might need a little, you know, pat on the back and a little more encouragement. But at the end of the day, if it's going to help them stay better, you know, and get better and have better QOL, they're going to do it. So don't be upset with me. I didn't say this, but, you know, there's some, like, thought out there that, you know, cervical cancer patients aren't compliant. They have cervical cancer because there was no pap smear. How can they be compliant with all of this eye care? It's so laborious. Like, what are your thoughts on that? I've never heard that. You don't want to hear that, do you? Because it's just not true. They just need support. Yeah. They just need support. This is what you want to get better. I want you to get better. This is our recipe. Right. And having somebody to have your back, I think, helps, too. If you have a phobia of drops or you can't remember to take your drops, especially with the individual vials, they look like trident gumsticks, and you just literally rip the cap off, put the drops in, and throw them away. But they're very small. So folks with arthritis or even a peripheral neuropathy, because I've heard this mentioned multiple times, have a really hard time touching, feeling, and manipulating the bottles. So sometimes having somebody who is like your co-caregiver, almost at home, is so important. And especially somebody, if you're not feeling well, to be your eyes on the road and bring you back and forth to appointments. I just want to piggyback a little bit on the types of drops. We use what's on formulary, too. And there are some steroids that have a decreased risk of cataract progression. And also, eye pressure increases. And so you might have heard of them, Lodimax, or sometimes Bexol. And we'll use them in addition to what's on Tier 1 of a lot of formularies, which is more in the prednisolone family, or dexamethasone. I believe we talked about it before. Dexamethasone was used because of the more global availability of that particular drop. But here in the United States, we've been using prednisolone acetate 1%. And that seems to work rather well. Great. I'll share a patient experience that I had. I had a patient, the last one I started on, to Sodamab. I counseled her through all the things. And this is the eye, and this is what we're going to do, and blah, blah, blah. And I got to Colpax last. And I told her about the Colpax, and you wear it during the infusion for 30 minutes, 30 minutes, like an hour of time total. And then I said, but you'll have to bring something else to do besides watch your phone or read or Netflix or whatever, because you'll have this eye pack on. And she lost it. That was kind of like, and I think it was building up, but just the stress of all of it, but that was the thing that just kind of pushed her over. And then she's not my 12-year-old teenager who can't put her phone down. She is a very successful business person, very reasonable, but that was just the thing that was like, ugh, I can't connect to the world for a whole hour. And so she clearly is coping with that really, really well, but it just was a wake-up call to me. I just didn't expect her to have that reaction. So then what was your response? Was it, we'll put your earbuds in for you. You can listen to music. I mean, did you have something at the ready to respond to her? Because I think that that is a valuable piece for this room, too. Yeah, I mean, I think organically, my instinct was just to validate that and comfort her and just, okay, let's come up with the, what are we going to do instead? She and I had a powwow about it, so she's doing audiobooks, just like you said, bring your earbuds. There you go. Yeah. I had a patient who I talked to about this, and after her first cycle, she's like, oh my God, this is the easiest thing. I think I had scared her so much and prepped her that she was like, this is a non-issue. But she's a personal trainer, and the neuropathy was something that she was more concerned about, and I know we kind of touched upon it a little bit. I just want to highlight it, because we do focus a lot of the eye toxicity, and we're lucky to have, many of us are lucky to have partners, but it is something to think about. And Dr. Birkenstock mentioned in her talk, there are kind of dose reductions or holding therapy that can help you strategize on how to best deliver this effective agent to your patients. So it is something that I also like to talk to about patients. Many of these patients have received Paclitaxel, so they may know what neuropathy is, but this is a little bit of a different neuropathy. So my patient's a personal trainer. She was just saying that she has trouble, like when she washes her hair, she feels it. So it's kind of like that proximal weakness that she was experiencing. So it is something to also remind your patients of and talk to them, and then dose reduce or hold therapy if it's becoming an issue. So I just, I didn't want that to fall by the wayside. Yeah, I'm glad you interjected that. That is really important, and honestly, like it took me a while to learn to recognize it, because the patient will come in. I mean, they won't say, oh, I have numbness and tingling. You know what that means. They'll say, oh, I couldn't get to the bathroom. What do you mean you couldn't get, well, you know, all these patients have fatigue, and they're tired, and there are disease-related symptoms. I couldn't get to the, what do you mean? I fell when I went to the bathroom. Okay, did you trip? No, every time I get up out of the bed, I fall down. Okay, that is like a warning sign that they may have a motor component, and we just partner with neurologists, and, which are also very hard for our patients to get into, and physical therapists, actually. So, you know, with Tisodamab and with our surgical prehab programs, we've gotten really friendly with our physical therapists, and patients freaking love physical therapy. Like, it changes their life to do physical therapy, and we, you know, I didn't use physical therapy that much until probably more recently in my career, and I guess I, you know, we just don't know how much our patients suffer, because they don't want to tell us. They want us, they are grateful that, you know, we're taking care of them, and we sometimes minimize, or just don't understand that they're suffering white knuckling, all that debilitation. Is that the right word? Yeah. Debilitation. Yeah. And especially, generally speaking, I've found that a lot of patients, they do thrive on the physical therapy. They feel like they're actively engaging in their treatment, they're doing something that boosts their endorphins, makes them feel better. Especially with gyne patients, you know, any physical therapy that involves a pelvic floor and trying to rebuild that is extraordinarily important. It is so overlooked and I know it's a little off topic, but since you brought it up, I wanted to throw that out there. Yeah, I think we need to be thinking about it when we're thinking about this neuropathy because clearly you're gonna hold the drug and get them to recover, but they're gonna recover faster if they're, and you're gonna get them back on treatment faster at a reduced dose if they're in therapy. And like you said, like it gives them something to do and they don't feel as anxious just waiting, you know, waiting, you know, I'm off treatment and I feel like crap, like I'm just sitting in limbo. They hate that, like probably more than anything. Great. Okay, let's see. We talked about monitoring and we talked about stopping. Great, those were the points, the high points that I wanted to hit. So thanks for going back through that. That was awesome. No problem. I'm still open for questions. All right, so we're gonna bring up your audience response again. What do you all think is most important to patient? You have to pick one here. I had an all the above, but that was too obvious. So we took that out. So we're gonna make you choose. What do you think is most important? And I'm sure this varies. All right. Has everybody voted? Wow, people just wanna live. I get that. That's what we think is most important. That's what- Do you agree? I agree. Yeah. I think that's what we think. We think that's the most important, but we worry that we're focused on the wrong endpoint a lot. I think we worry that we really should be more focused on quality of life and less focused on efficacy. But what do you think, Chandra? I think it's right on. Yeah. Yeah, I do think it's right on. And this just ties in back to that story that I shared earlier, that people pretty much do anything they have to do. If that's gonna get them another day of life, so. Yeah. And I mean, obviously there's variation in that, right? But I think it's more of a focal concern. Or, you know, that's the focal. That's what they're focused on. And that's also empowering to know as doctor. Oh, here comes quality of life. Good. Yeah. That's important too. It's definitely important too. Absolutely. All right. You can go to the next slide. Great. So for a moment, I'm gonna put Dr. Hayward on the spot just to kind of go over some really important points that she wanted to cover for the group. Thank you very much. A lot of this we've already discussed, but just to hit on a few points that we have not, I think another very important aspect of getting this therapy going at your infusion center and within your clinic is good education for your staff, for those nurses in the infusion center, understanding why these cold packs are so helpful. And in the infusion center, understanding why the drops are necessary. Also along that lines and just discussing the actual drops. And so what we do is we send a prescription to the patient. They pick it up from their pharmacy, but you have to keep reminding them sometimes to bring the drops with them because what happens if they show up with their infusion and they forgot that vasoconstrictor I dropped that they really just use the one time prior to infusion, then what do you do? And so some centers just keep extra bottles at their disposal in their infusion center. We have our specialty pharmacy onsite so we can do that. Any other? That's, yeah, that's what we do in that regard. Just something to keep in mind, making sure you have ample cooling packs and also keeping in mind that whatever cooling pack you might be using, you need to just stay cold for a while. And that might mean switching them out throughout the process as well. Also something that we've noticed as we began treating patients is anti-emetic therapy, so nausea, vomiting, and this is something that's come up with patients we initially didn't add it as a premedication but found that we should and we did. Just one agent of your choice, 5-HT3 antagonist, perhaps a steroid, maybe both. Also having that available for them at home. And also educating your clinic nurses for when they get those triage phone calls or whoever is answering those calls to have an idea of what that means and what they're looking for. We discussed establishing a relationship with your local eye care professional and how to connect even if they are not local and your patient has to see them outside of that. And then we talked about the various eye drop selections as well for the center. But then patient education and follow-up is just really having that navigator in place, having those continuous follow-ups, having good communication, setting realistic expectations for the patient. And then the other thing that we haven't touched on, I think, is some of the bleeding that we can see with this. I just tell patients, it's usually nosebleeds. It's usually nosebleeds and this is okay. And nose, bladder, vaginal, actually. Oh, as well, yes. Especially in the irradiated patients. So we'll see, but as far as what. Just like the trial, in my experience, it's been low-grade. Yes, yes, it's pretty minimal. It's interesting, it just kind of comes and goes, oddly enough. I'm not sure how to explain that, but it's probably just off and on tumor, anti-tumor effects. Yes, and along the lines of those patients that try to tough it out, you're right. Sometimes they don't tell you. It's just making sure to reiterate that if you don't tell me, I can't help you. So just that as well. Thank you. This is great, yeah. And I just want to continue to thank you guys for being engaged in the discussion. You bring so much to the table. I'm going to open, we're running a little bit ahead of time, so we want to open it up to some audience questions. You've got so many different perspectives and expertises up here on the stage, so we want to give you an opportunity to ask any burning questions that you might have. And it doesn't have to necessarily be about ocular toxicity or tisotamib, can be about cervical cancer in general. Just the floor's open. Well, I have a quick question. If a patient is insistent on wearing contact lenses, but is okay with just doing it as needed, when is the safest time for them to wear it? Is it after that 72 hours after the infusion? Is there a better time? That's a great question. We always counsel folks to not wear contact lenses in the presence of ocular steroids. So we use ocular steroids for a variety of things, postoperative care, uveitis, which is inflammation in the eye. And because of the risk of immunosuppression of the ocular surface, you're at higher risk of infections of the cornea. So we really, I would wait the 72 hours and then have that discussion, PRN use, lots of artificial tears. Yeah, I mean, I think technically it's best to just avoid them if you can for the surface toxicity, right, it can exacerbate that. So agree, so agree, yeah. The contact lenses just act as sponges and just pull the moisture right off the tear film. And if that's what's supplying your cornea with its nutrients, because it's avascular, I look at it as you're cutting off your oxygen and nutrient supply to the cornea. And sometimes that's how I rationalize it with the patient. But that's really what contact lenses do. Contacts are more toxic than to Sonomat. Once you become an ophthalmologist, yes, you would agree with that statement. Yeah, you know, it's funny you brought up the tears because I think it's good for them to have, I have this like chapstick addiction and I have chapstick like in my car and in my backpack and on my desk. You know, in all my offices. So I think the tears thing, artificial tears, is like they should kind of like plant them strategically so that when they need them, they use them. It's like your cheaters or your over-the-counter readers or those who are presbyopic, you have them all over your house, just put some tears with them and then you will have them everywhere. Oh, that's good to know. I literally want you to give me an exam after we're done with this. Oh, I get hugs too. I mean, I really get into it with them. I mean, you know, ocular adverse events are my thing. So we are really, yeah, that's good. You know, while we're waiting for folks to step up to the mic, you had said something about the patients toughing it out and that is so true. We've got, I can't tell you how many times that I've spoken with ladies and they've just like, well, I'm having this or this is happening or that's happening to my body and then they just kind of brush it off because they're like, I've got cancer. I'm going through all this toxic treatment. This is just part and parcel of how these treatments go. And I'm like, no, no, no, you've got to talk to your clinician. You got to let them know, you know, just any of the least little bit of things that are happening with you because chances are that they can help you manage that. And if you let it go too long, then it can really do some permanent damage. So it's tough. That really is a thing where they're, you know, it's that toughing it out syndrome. So I'm glad you brought that up. We're not going to let you guys leave unless somebody asks one question. You're on the hook. How many people in the audience have actually used Tisodamabidotin on a patient? So new experience? Yeah. All right. Oh, great. Yeah. Would you, can we put you on the spot and ask you to share your experience? Just like, how does your patient do? Would you mind to come to the mic so that everyone can hear? This is Dr. Christina Washington from Oklahoma who works with. I can't see. So I've had a handful of patients that we've put on Tisodamab in the past few months. Early on, getting some of the phone calls was very confusing because I didn't know what to do. So I had to do a lot of research on my own and reach out to some of the other people that we have supporting us like Sarah. But some of the toxicities that I've seen that I don't really know, didn't know what to do with were like fevers and things like that, which were not what I expected as well. But patients were able to tolerate the drug just fine and we are able to get them through the toxicities. But I haven't seen any weakness at all with it so far. So, yep. That's great. Thank you. Thanks for sharing. Well, I wanna devote the rest of this to our patient advocate because I think, you know, we don't get the opportunity to have you here with us, you know, very often on these panels. And this is why we do what we do. And if we, you know, forget that the patient's at the center of everything that we do, we're totally gonna miss the mark on the care that we're delivering. So I'm gonna bring up your points. And I'm gonna give you the floor and we're gonna respond to you, so you're in charge. Thank you. So again, my name's Chandra Hall. I was diagnosed in 1998. My husband and I were fairly newly married, trying to start a family after a year, couldn't get pregnant and surprise, cervix cancer, immediate hysterectomy, no kids. And so if that hadn't happened, I wouldn't be here with you today. And so I wanna thank C-Gen. I wanna thank GenMab, of course, our panelists here because it's pretty incredible that a terrified 28-year-old girl who's having a major, major surgery and finding out she's never gonna have her husband's kids is sitting up here with you learned folks today. So the fact that you are in this industry and trying to save lives, let me tell you that there are tens of thousands of us across the country that have so much love and appreciation for what you do. So all the clinical information aside, the consistent feedback and conversations that I've had with other survivors are, they wanna know, am I gonna die? Am I gonna die? And if so, when? And how, while I'm still surviving and while I'm still alive, how bad are those treatments going to make me feel? But the one thing that I certainly experienced privately that I did not share was about my sexual health. I was 28. I was newly married. And so there was no conversation with my gynecologist. They didn't bring it up. They didn't let me know that because I was able to at least keep my ovaries that I could have a gestational carrier surrogate. So it really wasn't until I was older that I found out that that was even an option for me. So once you get past all of the clinical and treatment conversations you have with your patients, it is so important to have the sexual health conversations because that is part of quality of life. So many gals I talk to have internal brachy and their vaginas are fused shut and they've got the scar tissue and they've been given these clinical dilators that are horrible. They don't know how to use them. Thank God for YouTube. I just had a conversation in a meeting, lunch meeting with a gal last week. She's had a pelvic exoneration, cervix cancer twice, pelvic exoneration. She's 30. She just graduated while she was going to medical school to become a gynecologic oncologist. Thank you very much. And there's just no conversation around that. And you have to have those conversations with your patients because it is important to them. And they're too embarrassed or too terrified to bring it up with you. But you, if you're truly invested in their overall health and their overall treatment, you're gonna bring that up. You know, all patients should be assigned a nurse navigator. We talked about it. I know it's not an option for some of you, but those nurse navigators can then help them get with sexual health counselors, can help them get with psychologists, psychiatrists. I remember my gyne, he put me in a private room back then. And he said, I'm gonna put you in a private room because we found that in addition to all the surgical things that are going on, a lot of women, especially younger ladies that lose their fertility have a whole host of emotional baggage that comes along with that. And he wanted me to be able to grieve that in private without another patient in the room with me and their family listening to all my business. So I love him for that. You know, again, getting back to the hub and spoke model, you know, so many women in many cultures are the hub of the family. And so when they're also newly diagnosed, they're like, oh, you know, how sick is this gonna make me? Can I still get my kids to school? If not, how are they gonna get to school? What if I live on a reservation? What if I am in a rural setting? How am I gonna get to my treatments, how am I gonna live my life with as little disruption as possible? And that's where those nurse navigators and social workers come in and they're so wonderful because they can help them get connected to all those resources without necessarily having to go out and do everything themselves and try and get online if they have access to the internet. You know, I really, it's just such a comprehensive disease, gynecologic cancers, it's just not an organ. And it really takes people who really give a crap about their patients and have to invest in them comprehensively. I can't just be a six minute clinical visit, I just can't because it affects all of them, it affects their community, it affects their family unit, it affects their work, not that other cancers don't, they certainly do. But again, gynecologic cancers are just such a different, different dynamic than any other kinds of cancers. And I, you know, here, I'm 20 some years out, I still get joked up about it, I'm kind of proud that I'm not shedding tears right now, but my own parents, and another aspect where you're so valuable to your patients, my own parents were ashamed that I got cervix cancer, they wouldn't talk about it, they didn't tell anybody in the family, I had to do all that myself. My colleague, you know, when she disclosed she had an HPV related cancer, her colleagues said to her, well, isn't cervix cancer the whore cancer? Why? So this is the kind of stuff we're dealing with from our friends and our family. So the more time you can just really take the time and draw those questions out of them, because we as a patient, especially a newly diagnosed, terrified patient, we are feeling like we're wasting your time. We don't wanna ask you questions that we're afraid to ask, because we know how busy you are, we know you gotta turn the room over, we know you got other terrified patients waiting to get their diagnosis. And so I would just ask that you continue to draw those questions out of them, continue to ask them about what's going on in their life. So many times I've heard where the patient's waiting in the room, clinician comes in, so how are we doing today? It's like, well, I freaking have cancer, dude, what do you expect I'm doing today? You know, and I know that that's the way you need to approach your patients, but I would just ask that you just, in this setting, just take a little bit of extra time to ask the extra questions, to make sure you really are giving them the best treatment and the best care, and you're treating them as the whole patient. And the fact that we have our eye doctor and our pharmacist here with us today, it just warms my heart, because they're vested too, and this is the way that they can also make a difference with their patients and being here and learning more about these diseases and these treatments. So I'll tee it back over to you, but I think I've gotten everything out that I wanted to say. Gosh, well that, I mean, come on, that was amazing. Um. One more thing. Go ahead, I'm a little speechless, you go ahead. The National Cervical Cancer Coalition has chapters across the country, and we are grassroots, we don't take paychecks, and we have advocates that wanna help you. So wherever your practice is, I would ask that you reach out to the National Cervical Cancer Coalition, because our patient advocates want to be a bridge for your patients. We wanna help them navigate what they're going through because we've been there, and we've gone through it. And we wanna give them a shoulder to cry on, and we wanna give them an outlet. So nccc-online.org, we've been around for 20 some years, we are under the American Sexual Health Association now, who is, again, an amazing resource, especially for those that are having sexual dysfunction or sexual challenges, sexual health challenges. So keep in mind, the American Sexual Health Association is also here to help you with all of that. Okay. That's a great resource. And I think the conclusion is the same as the beginning, is that it does take a village to really do this well. You have a good friend that says, anyone can do cancer care poorly, but it's very hard to do it well. And so I think all of us wanna strive to do it well. And I know certainly that's the mission of the society, the IGCS. Great. Thank everyone so much for being on the panel today. You're wonderful. Another round of applause. So this concludes the symposium. Thanks to our presenters, panel members, and our audience for joining us this afternoon. The session will be available as part of the IGCS On Demand program following the meeting. And the GOG Foundation and GOG partners would, again, like to thank our industry supporters for this symposium, Sijin and Jen Mabb, and have a great afternoon. Thanks, everyone.

Tisotamab

cervical cancer treatment

FDA approvals

immunotherapy

patient outcomes

ocular toxicity

eye exams

prophylactic steroid eye drops

vasoconstrictor eye drops

lubricating eye drops

ophthalmologist

patient understanding