Welcome everyone. My name is Rithi Solani and I'm the IGCS Education Committee Chair and Director of Division of Gynecologic Oncology and Professor of Obstetrics and Gynecology at UCLA in Los Angeles. I would like to welcome you to today's team report, How New Data in Cervical Cancer Affects Second Line Treatment Options, which is supported in part by CGen. IGCS is committed to meaningful opportunities to our industry colleagues to gain exposure to our gynecologic oncology community through a unique year-long educational program. This platform provides a level of strategic engagement and exposure needed to educate and inform gynecologic oncology professionals on current and future treatments to optimize patient care locally and globally. Before we get started, I wanna mention a few housekeeping items. We will have interactive polls and I encourage you to participate in them. If you have any questions, please submit them via the Q&A feature and we will do our best to answer these questions. Lastly, a recording of this webinar will be available on the new IGCS Education 360 Learning Portal, which launches this Tuesday, September 6th. This is a society's first ever learning management system and I encourage you all to visit next week. It's really impressive. So let's start by meeting our panelists. It is so wonderful to be with true experts in the field of cervical cancer, Dr. Nicoletta Colombo and Dr. Leslie Randall here today with us. Thank you both for joining us. If you would both please introduce yourself. Dr. Colombo, I'd like to first start with you. Yes, hi. Very nice to be with you today, this evening for me and afternoon for you. My name is Nicoletta Colombo and I am from the University of Milano Bicocca and I'm the Chair of Gynecologic Oncology Program at the European Institute of Oncology in Milan, Italy. Wonderful, we're so lucky to have you here with us. And Dr. Randall, please introduce yourself. Thanks so much. So great to be with all of you today and I see some familiar faces or names in the participants. So hello to everyone from Richmond, Virginia. I'm the Division Director of Gynecologic Oncology here at Virginia Commonwealth University. And I'm also the Cervical Cancer Advisor for the clinical trials and GOG partners. So really happy to be here today to talk about these great new developments in cervical cancer. It's our pleasure and I welcome both of you. And let's begin with a case presentation and our first polling question. So a 34 year old woman was diagnosed with stage 1B1 cervical cancer and undergoes a radical hysterectomy. The lesion is 1.8 centimeters with less than one third cervical invasion. Lymph nodes are negative although there is LVSI. She does well until about a year and a half out from surgery when she presents with an unresectable pulmonary recurrence. A PET CT scan is otherwise negative and the tumor is PDL1 positive. A clinical trial is not available. What is your treatment recommendation? So one platinum taxane, two platinum taxane bevacizumab, three platinum taxane pembrolizumab, four platinum taxane bevacizumab and pembrolizumab or five other. And we'll give you a moment to get your answers in. And team, do we want to share the results? You should see the results. Sorry. Oh, I'm sorry. Okay, great. And so a little bit of a wide variety here where you can see kind of a fair distribution across all boards with the kind of majority being platinum taxing, Bev and Pembroke. So I'm looking forward to hearing more on this. All right, let's go to our next poll. So she has a complete response to platinum taxing, Bevis's map and Pemberley's map after six cycles of chemotherapy, and she tolerates therapy without significant side effects. She completes eight cycles of Pemberley's map and Bevis's map following this. What do you do now? Do you continue the Pemberley's map and Bevis's map? Do you stop the Pemberley's map and Bevis's map? Do you stop the Bevis's map and continue Pemberley's map only? Or do you stop both? Okay, and it looks like a majority would continue the pepperless map and Bethesda's map. So once again, we'll hear a little bit more about this. But this is really, really great. And they can see the results, correct? I showed them to me. Okay, perfect. Thank you. Sorry. All right. Next slide. All right. Well, it's now my pleasure to turn it over to review Kino 826 data to Dr. Colombo. Okay, thank you. Thank you very much. Yes, so I would like to start with the NCCN guidelines, 2022. And as you can see, as first line combinational therapy, the preferred regimens should be pembrolizumab plus cisplatin paclitaxel plus or minus vivacizumab for PD-L1 positive tumors. Or you can use pembrolizumab plus carboplatin paclitaxel with or without vivacizumab again for PD-L1 positive tumors. So actually this patient had PD-L1 positive tumor. And I think the correct answer for me would be pembrolizumab together with chemotherapy and personally also in a 34 year old with vivacizumab. So can I have the next slide? Can we see which are the data supporting these recommendations? This is the Kino 826. As you know, it was a randomized double blind phase three study, including patients with persistent recurrent or metastatic cervical cancer not amenable to curative treatment without prior systemic chemotherapy. So this was a frontline treatment. And they were randomized to receive the standard of care chemotherapy, which was carboplatin or cisplatin with paclitaxel and together with pembrolizumab or placebo. They also could be treated with vivacizumab. So the choice to use vivacizumab was actually left to the physician. And of course, this was related also to possible contraindication that, as you may know, sometimes in cervical cancer are quite frequent contraindication to vivacizumab. So pembrolizumab was given for two years, so 200 milligrams Q3 weeks for up to 35 cycles. And vivacizumab was given, in fact, without a specific duration. And the dual primary endpoint of the study was overall survival and progression-free survival per race is the 1.1 by investigators. Also you see the stratification factors, which were metastatic disease diagnosis, yes versus no, and the PD-L1 CPS score less than 1 versus 1 to 10 and more than 10. And the use of vivacizumab. Next slide, please. Okay, so this is the outcome in the old-comer population. As you know, we tested both progression-free survival and overall survival in these three different populations according to the CPS score, 1 and higher, old-comer, and 10 and higher. So these are the results for the old-comer population. And the addition of pembrolizumab to standard of care provided a benefit in both progression-free survival and overall survival. As you can see, the hazard ratio is 0.65 for progression-free survival and for overall survival is 0.67. So a clear and significant benefit with the addition of pembrolizumab to standard of care chemotherapy with or without vivacizumab. Next. What is for me extremely important is also to see that this treatment was associated with a better quality of life. As you know, it's very difficult to find any study where you can demonstrate an improvement in quality of life. And this is one of the fewer studies where a clear benefit in quality of life was demonstrated, which is quite understandable because, as you know, cervical cancer is very often a symptomatic disease when it is advanced and recurrent. So if you are able to control the disease, you should also be able to achieve an improvement in quality of life. And this was the case in Keynote 826. Next. In the original paper, we presented the forest plot for the pre-specified subgroup analysis, but this is a post-hoc analysis which was recently presented this year at ASCO. And we look at the efficacy of the addition of pembrolizumab in different subgroups, specifically according to histology, so squamous and no squamous, the use of carboplatin or cisplatin, the concomitant vivacizumab, yes or no, and also the prior chemoradiation therapy. And as you can see, the benefit for the old camera population and the CPS1 and higher was quite confirmed for all the subgroups that were analysed. So that's very important to keep in mind. Next. Okay, so I think that were the main results of Keynote 826. I think this is definitely a practice-changing study because as you have seen, the NCCN guidelines in fact report this as a new standard of care. Yeah, I couldn't say it better. I think that's perfect. And congratulations to you and the cooperative groups for this amazing study that's really revolutionized cervical cancer care. We do have a question in the Q&A, so I want to do this poll and then we'll do the question. And if you guys have other questions, please do submit them. So this case where we had this patient who had this pulmonary recurrence, the pembrolizumab was stopped and she's maintained on vivacizumab. And approximately one year later, she has new multiple pulmonary metastases. What would be your treatment at this time now? So platinum-based chemotherapy, non-platinum-based chemotherapy, three, restart the pembrolizumab, four, combination IO or immuno-oncology therapy, five, tacetamab, vidotin, six, hospice, seven, other. Okay, so it looks like a kind of a wide variety here with Tisotamabadotan having the most votes, so we're going to hear a little bit more about that. But there was an interesting question in the Q&A, and so I'll pose this to our panelists. The question is, if a single site recurrence, even if it's unresectable, why not give local high-dose palliative radiotherapy and keep systemic treatment in reserve? I'd love to hear your thoughts on this. Either way. Yeah, well, I think, of course, if this is feasible, I mean, I didn't prepare this case, but I thought that surgery was excluded, and I thought also for some reason radiotherapy was excluded. Because indeed, when we have an oligometastatic disease, you may consider for sure a local treatment, either surgery or radiotherapy. So I think that could be an option. My idea for this case was that, for some reason, this was not possible. So that's why I think it's important to go for systemic treatment. Yeah. And I agree with that. That's how I kind of read it. But I think it's a good thought to have. Dr. Randall, any thoughts? No, I agree with that completely, especially oligometastatic, try a surgical or a radiotherapy option. I see another comment kind of popping up here of SBRT. Maybe we should have made it a little bit more obvious that it was a systemic therapy case for discussion's sake, but no, these are very, very good points. But clearly, I mean, anytime you have distant metastatic disease from the initial site, that's hematogenously spread, and you can almost assume that eventually you'll have more hematogenous disease pop up, but surely that could sort of improve or add some survival time. Yeah, great. Great questions. All right. And we'll go back to the slides. Okay. Dr. Randall. Great. So it's so, I love a little bit of a challenge. And so it looks like our second line choices are kind of very widely distributed there. I think that I'm going to try to convince you that really the next go-to treatment would be, next slide, to sodum abvidotum. And for reasons that, number one, really, we don't really have any data yet on checkpoint after checkpoint. So I'm not sure how far you would get adding back single agent pembrolizumab possibly. And this is one of the choices, and some of you picked this, was doing an IO combo, but we don't really have any data on that either. So switching to a different type of therapy or a cytotoxic therapy may be the better way to go. We don't have a lot of data on platinum after platinum in the second and third line. We do have data from the EMPOWER study on kind of the modern era response rate to chemotherapy. And in the physician's choice chemotherapy arm of EMPOWER, the response rate was 6%. And we sort of point estimated it to be around 10 to 15%. And six was much, much lower than that. And so I think that just maybe reflects our more modern treatment paradigms and what we can expect. So keep that 6% in mind as we sort of talk here about Tisodamabidotin. If you're not familiar with this drug, it's an antibody drug conjugate, the first one approved in GYN oncology, which is fun for those of us that do cervical cancer research, but we rarely get the first of anything. So this was the first ADC, and it targets tissue factor and it binds with a linker monomethyl or a statin ear MMAE as its payload. And so as you can see in this diagram here, the antibody binds to tissue factor, it's brought into the cell, the linker releases the MMAE, which has a direct cytotoxic effect. When that cell dies, the MMAE is released into the microenvironment, causing a bystander cytotoxic effect on the surrounding cells and potentially even an immunologic type of reaction in the microenvironment. And you can see that that's the antibody dependent cellular phagocytosis and cellular cytotoxicity. So this drug may be working by multiple mechanisms of action. Next slide. So this is the first study that established the efficacy of Tisodamabidotin. This is a great partnership, you'll see many of these GOG NGOT partnerships coming online. Studies that are getting these drugs approved, this study got this drug approved in the United States under an accelerated approval mechanism. Of course, other countries are awaiting the availability of this drug. This study was a single arm phase two trial that enrolled 101 patients. And these were patients in the second and third line. So they had progressed on prior platinum-based chemotherapy with Bevacizumab if they were eligible. This study was done in the era prior to Pembrolizumab being available in the front line. So these are not necessarily Pembrolizumab treatments, but could be had they gotten in the second line. So Tisodamabidotin was given to these patients, open label, two mgs per kg every three weeks intravenously, and it was continued until progression or unacceptable toxicity. And for the accelerated approval, the primary endpoint was an objective response rate measured by RESIST 1.1 by an independent central radiologic review. And the secondary endpoints were duration of response, time to treatment response, progression free survival by both independent review and the investigator, toxicity, overall survival, and health related quality of life. Next slide. So these were the results that we saw. We had seven complete responses in this sample and 17 partial responses for a complete objective response rate of 24%, which again far exceeds that 6% and 6% chemo responses even excluded from the 95% confidence interval that surrounds the 24%, because the confidence intervals are important, especially when you've got a smaller sample size. Next slide. Oh, and this is the accelerated approval that was granted back in September, which was about three weeks ahead of its expected date. Next slide. So these are the most common adverse events noted with Tisodamabidotin. You can see alopecia, epistaxis, and if you look across here, there are several ocular side effects. And this is sort of the special AE of interest with Tisodamabidotin. Most of these are low grade. Most of these are reversible when the treatment is held and or dose reduced. Next slide. And these are those other AEs of interest to include the ocular are bleeding because this does target tissue factor, which is in the coagulation pathway. There was low grade bleeding seen with TB, but rarely high grade bleeding. And then the last AE of interest that in my mind, and in my practice has been the one that's a little bit more difficult to manage or more concerning than really any ocular or bleeding side effects or peripheral neuropathy. So clearly patients that are coming into this therapy have been most of the time pretreated with Paclitaxel. They should have a grade one or less baseline peripheral neuropathy to go on this therapy. And as you can see here, some patients did experience a higher grade neuropathy, 9% at grade two, 7% at grade three, and then a bulk of patients having grade one neuropathy. The neuropathy with TB is different than the toxin neuropathy. It's not just a sensory. It can also be a motor neuropathy. It can be somewhat of a central neuropathy and patients often won't really complain of the typical symptoms. They'll say things like, I had trouble getting to the bathroom. What do you mean? Well, I fell down. That's how you start to notice these neuropathies associated with TB. Next slide. I think we're back to our poll. Yeah. So thank you. That was a great overview. So one additional poll question here. So what do you see to our audience? What do you see as a future frontline therapy for advanced recurrent cervical cancer? Platinum taxane, Pembro plus Bev, plus Tisodamab, and I'm sorry, I forgot, I skipped the first one here. Platinum taxane, Pembro Bev. Platinum taxane, platinum plus taxane, plus a PD-L1 or PD-1 inhibitor, plus a CTLA-4 inhibitor, plus or minus Befacizumab. Oh, these are hard to read. Platinum plus or minus an IO plus CTLA-4 inhibitor plus Befacizumab. Tisodamab, a dotin plus an IO plus CTLA-4 plus Befacizumab, IO plus CTLA plus Befacizumab, or something else. I might have confused you by reading this, so I'll just let you sit down. Yeah, that's a mouthful. I'm glad I can't vote. This is hard. These are all exciting. I agree, and I think we're going to hear a little bit more exciting data about what's to come, so this is really, really exciting to see. So here you can see the results. A majority of almost 50% of folks picked four or five drug regimens. So I think it'll be really exciting to see what's kind of on the horizon and what actually happens. So I don't see any other Q&As from the audience, but I'd love to hear, Dr. Randall, what do you think? Yeah, I love that. I don't know, can we put the poll back up because I don't have very good memory. I just have to look at it. I think, you know, it's really interesting. Thank you. It's interesting. You know, I've convinced you a little bit that Tisodamab is a good drug for cervical cancer. I'm glad of that. I think that I love the, you know, it is gonna be hard to beat Kenoate 826. The overall survival in Kenoate 826 with the addition of Pembrolizumab is what, Nicoletta, 24 months. I mean, it's just really remarkable. So you have a patient with metastatic disease sitting in front of you, and it's the median overall survival with that treatment regimen is 24 months. I mean, that's just not something that happened five years ago in cervical cancer at all. So I think, you know, at a minimum, patients need to continue to receive platinum taxing with Pembrolizumab, with Bevacizumab if they're candidates. And I could, I don't think you could give the taxing and the Tisodamab together because of the neuropathy and really the mechanism of action of MMAE, which I didn't mention, is that it's a microtubule poison, much like taxane. So I think the sweet spot might be this second option where you replace the taxane with Tisodamab-vidotin. I think that's really exciting option. You know, this single agent, this PD-1 CTLA-4 combo is really interesting. And we saw data, Checkmate 358 of high response rates in the frontline for patients. I think there's more to come in the future on that, but don't count that out. But that's definitely not ready for primetime in the frontline because Keynote 826 was so positive and so successful. Yeah, I believe there's gonna be an update of Checkmate 358 at ESMO this year. So we're looking forward to hearing that. Dr. Colombo, what are your thoughts? Yeah, well, I do agree. I want to see in my regimen for sure Pembrolizumab and Bevacizumab, I think these are crucial and platinum so far, I think. And I agree, I would possibly substitute taxane with TB if, you know, if we can prove and maybe we will see some data on this combination. So I think that would be probably my choice, my first choice. Of course, as you said, it's very interesting also the dual blockade. So there are trials ongoing, but we don't have data yet. So basically I want to have a IO either alone or in combination and Bev, because I think they're very crucial and platinum. And then yes, I think probably TB with platinum would be my choice. Yeah, I mean, I agree with everything you guys said. And I think the interesting thing, Dr. Colombo, that you shared was the quality of life data. And I think that's really important to kind of continue to monitor for these patients as we get more sophisticated with our regimen. So continue to look at how that impacts not only the outcome data, but how the quality of life impacts our patients as well. A really provocative, I think really exciting. You know, we have talked about how there was a long pause in cervical cancer updates until recently. So really robust and exciting studies coming out. And I agree, I think checkpoint inhibitors are definite in cervical cancer frontline. And so what we add to it or how the combinations are what I think are interesting to explore. All right, next slide please. All right, Dr. Randall, I think I'm gonna turn it back over to you. Great, so what's coming with TB and we're already starting to work on this and presented the toxicity data from this study, this follow-on study to the single agent TB at an IGCS. I think it was last year, but I've lost track of my years with all these virtual meetings. I believe it was last year's IGCS presented by Dr. Monk. But this is a trial looking at not only, it's looking at TB in combination with Pembro, Lizumab and Carboplatin. It's looking at it in both the frontline with Pembro and in the second line with Pembro and then in the frontline with Carboplatin. So we just talked about potentially substituting out pathway tag cell for TB and here's some data, preliminary data on that. So this is the design of the study. It was a little bit complicated. There was a phase one B dose escalation of the combinations. There were no DLTs seen in that and the both drugs, each, gosh, I'm tripping on my words. So each drug can be given at its standard single agent dose in the combinations. And so those were expanded in the phase two setting in about 30 to 35 patients, depending on the setting. And you can see that here on the slide and objective response rate is the primary endpoint in the phase two expansion as was the primary endpoint for the TB single agent study. So you can go to the next slide. So Dr. Vergoat presented these data that I found to be really exciting. So I told you the response rate with TB alone. Oh, sorry, this is frontline. So frontline, the response rate for chemo Bev is 50%. Pembro takes that up to about 65%. Here frontline TB with Pembro, the response rate here is about 41%. So just not exactly, not as good as what we saw with the chemo quad or even the triplet of platinum taxing a Pembrolizumab without Bevacizumab. But certainly interesting for patients who aren't candidates for platinum or who wouldn't be candidates for a multi-agent treatment. This might be an option. Now, this is just preliminary data and this is not definitive data yet. And so this doesn't support its use currently in the frontline, but it's certainly provocative data. Next slide. And so here's frontline TB with carboplatin and you can see a response rate here coming up to 55%, getting closer to what we saw with Bev, closer to what we saw with chemo Pembrolizumab and 826. But certainly, and again, an option for patients who can't tolerate quad therapy, but again, not ready for use alone in this setting, still investigational. Next slide. And then here is what actually we're using in some cases here in the US is second, third line TB with Pembrolizumab. The combined objective response rate, you can see there on the left, 38% compared to 24 with TB alone, compared to 14 with Pembrolizumab alone. So it appears to be more effective to get this together. This is independent of PD-L1 status. This is not approved as a combination, but because we have availability, at least in the US, of Pembrolizumab in a second line and third and TB in the second, third line, you can give this to patients who have not received Pembrolizumab yet in the frontline. So we still have some of these patients. I think, obviously, these patients are going to be fewer and fewer as Pembro continues to be taken up in the frontline. I probably wouldn't give Pembro again in the second line unless a patient had had a long Pembro-free interval. I'm making that up. There's no data to support that. And just like we had mentioned before when considering giving Pembro again after having received it in the frontline. So next slide. I think that's all I had there. Great. This is a great review, and I just want to thank both of you. But before we go, there is one more question, and I think it's a really interesting question, once again. So thank you for the audience for participating and submitting questions. But looking at toxicity and non-curability of recurrent cervical cancer, should one start systemic chemotherapy in asymptomatic patients? Okay, maybe I can start. I don't agree with this statement about uncurability. I must say that with these new agents, we are now seeing something we have never seen before. And I'm talking about both Bevacizumab and Pembrolizumab. And really every day we are discussing some clinical situation that we were not used to. I give you an example. Sometimes you might have a patient candidate for exenteration, and we sometimes use neoadjuvant chemotherapy because we want to decrease the tumor size and make the patient more operable. And we faced a few times this situation where the response by using not only chemo, but also Bevacizumab, for instance, and Pembrolizumab, you achieve a complete response. And now we are in doubt what to do, whether to perform exenteration or not, because we were not expecting a complete response. And some of these, I can tell you, are long lasting. And so I think really the landscape is completely changing. And so that's my point. Of course, most of these patients are uncurable, I agree. But I wouldn't say that all of them are uncurable. So that's why I think it's worth it trying to use our best treatment, particularly if they are fit, if they are young and so on, because actually you can reach some unprecedented results with these new drugs. So that's my point. I don't know what you think. I could not have said that better myself. And we've definitely seen it. We've seen these complete responses. We've seen these sustained responses. I've gotten, I have a lot of faith that we may actually be seeing not just rare cures, but a fair number of cures. And you don't wanna say it right until you actually have the data to really support that. But yeah, I think especially with these agents and they're tolerable. I think for, especially for this audience, international, the real challenge is just access. And really it's probably the places that will need these therapies the most may or may not have access to these treatments. And I think that's really a disservice, but having the dialogue that it's not just, it's not just palliative therapy necessarily may help some of these, may help some of these countries get access to these treatments. Yeah, I had a mentor who once said the best time to treat the patient is a week before she develops symptoms, right? Kind of jokingly. And I think the key is you wanna make sure you're treating these patients. I mean, as soon as you recognize that there's disease recurrence, but we don't wanna wait until these patients get sick and we know that things can become catastrophic quickly. So I think one really compelling thing, and it's very anecdotal, but you see the complete response rate with Tisodamath and Pembro alone at 12%, right? And what the duration of that is not known yet. But when you're looking at carboplatin or platinum taxane and bevacizumab from GOG240, it was 8%. And now you have two agents that are kind of challenging that. So I really do think, even though it's a small percentage difference, I really do think it's a tell that we are kind of really attacking the biology of disease. And so I think that's really compelling. There's a couple more questions coming in. For patients that achieve a complete response on immunotherapy-based treatment, how many cycles past a negative scan should we treat? So Dr. Colombo, I'll turn this over to you. Well, I would stick with the Keynote 826 regimen. So it's two years of Pembro. Maybe in the future, we will try to decrease this, but the good results came with this duration. So I would like to stay with this duration of treatment for Pembro, actually. You know, 35 cycles every three weeks, or yeah, that's worst. And one of the most brilliant things was to have that maintenance strategy kind of built in. I think that really kind of helped reduce some of the toxicities and kept patients on instead of the full regimen. There are a couple of attendees who have their hands up, and I'm gonna allow you to talk if you do have a question. If you don't, you can put your hand down, but Sergio Nicolau, did you have a question? You can unmute yourself if you do. Oh, sorry. I think I pressed that. You can just say hi. Well, you're welcome. Hi, thank you. Sorry, sorry. No worries. Thank you for joining us. And then I have Venia Van Herp here, and I apologize if I mispronounce your name. Did you have a question? You can unmute yourself, and we'd love to hear from you. No, I don't have a question, but thank you. Thank you for being with us. No, thank you for being here. All right, and I have one more. Dr. Narayan, go ahead and unmute yourself and ask your question. Well, I think if we start treatment with asymptomatic patient, and if they develop drug resistance, and when they become symptomatic, we actually don't have anything to offer. So the question of drug resistance being developed in treating patients who are not symptomatic and getting toxicity of treatment. So just for the benefit of one or 2% patient, who you think are going to be long-term survival, is it actually rational? Well, as we said, I think Ritu said very well. I may agree that you don't have to start when they are totally asymptomatic, but on the other hand, you don't have to wait too much and too long because sometimes they can go very quickly. And so then the patient is not fit anymore to tolerate treatment. So I think it's difficult to decide that it's a very subtle boundary. But I think, yeah, of course, if you have a completely asymptomatic disease, you may want to start, you may want to wait. But actually, I wouldn't wait too long. That's my point. Yeah, I think the beauty of the novel treatment options are that they aren't as toxic as our prior options and they have durable responses. So when all we had was platinum and taxane, you would do an induction cycle, patient would most likely have some level of a response to that, but then that response is not durable. You have to continue the treatment for the disease to stay for that, to continue that response. But now that with these Bevacizumab, Pembro, TV, they're much better tolerated in the longterm. You continue them as sort of this maintenance and their responses are durable. So I think now that we're shifting away from those older cytotoxic treatments that weren't as effective, that led us to develop sort of these paradigms in breeding toxicity and resistance and waiting to treat the patient and keep the therapy kind of in your back pocket for later, like these newer treatments sort of challenge those paradigms in my mind. Yeah, I agree. And I think your point, Dr. Narayan, is very well taken that until we know that this actually has an impact on survival, it's gonna be a question that nobody's gonna have the right answer to. But I do think that we are making progress. And I think this is something that our patients, rainy day is today, so we're not saving anything for the future. The reason for my asking this question was that when the Bevacizumab trial was first published, they registered improvement or median survival by three months. So from 15 months, it became 18 months. So I went back to my database and I looked at all the patients who recorded cervix cancer. And in Melbourne, we do not, if it is palliative radiotherapy can be given, then at least in the beginning before the trial, we would not start chemotherapy straight away. So when I looked at the median survival of all relapsed patients, it was already 18 months. But I agree that it was a prospective database collection and I did not plan in any prospective sort of study. So the median survival in my database turned out to be 18 months, even without doing any. So my argument was that when they become symptomatic and then you add all these things, you may be able to extend survival even more. Yeah, it's a great comment. And I don't know if Dr. Colombo from the database for 826 recurrent patients, if it was recorded on who had symptoms and who didn't. No, I don't think, you know, I'm trying to imagine which kind of patients with recurrent ovarian cancer does not have symptoms. You know, I don't understand what you mean. Probably these are patients with just isolated lung metastasis, something like that, because otherwise I cannot imagine a patient with relapsing cervix cancer without symptoms really. I don't know which kind of patients you are referring to. We have two more questions. I'm hoping to get to it, but this is a really provocative discussion, but you know, we're a little bit over and I want to give everybody a chance. So we'll just do two more questions and we'll close out if that's okay. Maxwell Chimina, if you could unmute yourself, we'd love to hear your comment. You're still on mute. I don't know if, or we can come back to you. And then I have Adrian Meyer. I'm sorry, Ming-Yin Lin. Do you have a comment or a question? I guess the question I had, I guess it just depends because I would imagine in the context of a clinical trial, patients are being screened regularly or restaged. So asymptomatic recurrences would be detected. I think, I guess, outside the context of a clinical trial, there isn't actually any clear evidence of how often or if any, you know, there's any worth screening or imaging asymptomatic patients. So I think that's why it's difficult to compare, you know, trial patients versus non-trial. That's my comment. And the question comes back to, now that we've got these agents, should there be screening and can we justify the additional cost then? I might not be framing this question very well, but that's just my thought. I have that same burning question every day. You know, I'm very passionate about surveillance and minimizing over-utilization of tests that don't impact survival. And I think we abuse that to some degree. I think your question is right on. And that's why I think looking at a prospective study, you know, kind of retrospectively or ad hoc to see if you can tease that out. But I think Dr. Colombo brings up a great point that, you know, many of these patients probably do have symptoms and it's, you know, outside of those clinical trials where we are scanning them, we probably aren't detecting a lot of asymptomatic unless you're doing routine surveillance, which I don't support, but is done. I think those are great questions. It's something we should probably think about incorporating into future studies. Before we close, just like to give Dr. Randall and Dr. Colombo another chance, one last point to leave the audience with. No, I think it's an exciting time for me. I mean, cervical cancer now is, you know, there was nothing until very recently. We could not use anything. And now we have so many drugs and so many trials ongoing for the future. So I think it is an extremely exciting moment for our patients. I couldn't agree more. And, you know, I'll say it again, like these are so effective and tolerable and I'm so passionate about it that I just, you know, I wish there was a way to get this into the places that really need it. We know that cervical cancer happens in low resource settings and not all, there's plenty of it in the high resource setting as well, but just to be able to distribute the drugs where they need to be is really my passion. Well, thank you to both of you guys. This was really informative, excellent presentations. And we are so lucky to have, you know, experts in our field here engaging with us live. So, and to our audience, thank you for your time and your questions and participation. We really, really appreciate it and look forward to providing you with more educational opportunities. In closing, we are gonna record this and it'll be available on the IGCS Education 360 Learning Portal, which I'm sure you will check out. It will be available on September 6th and igcs.org has a preview of this portal. So make sure to look at that. And lastly, if you are not already registered, please join us in New York City for the IGCS Annual Global Meeting on September 29th to October 1st. You can visit igcs2022, 2022.com for more information. And we really do hope to see you there. We wish you all continued health and safety. Thank you so much for your time and participation today. And to our panelists, a very sincere thank you was amazing. Thank you. Thank you. Bye-bye. Bye.

cervical cancer

second-line treatment options

Rithi Solani

KINO 826 study

pembrolizumab

tisodamab vedotin

personalized treatment decisions

patient outcomes