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Latest Advances With Targeted Therapies for Advanced/Metastatic Urothelial Carcinoma: Evidence and Implications

  • Authors: Thomas Powles, MBBS, MRCP, MD; Yohann Loriot, MD, PhD; Jonathan Rosenberg, MD
  • CPD Released: 12/10/2021
  • Valid for credit through: 12/10/2022
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Target Audience and Goal Statement

This educational activity is intended for an international audience of non-US hematology and oncology specialists, urologists and pathologists.

The goal of this activity is to increase physician knowledge of the rationale and available evidence for emerging targeted therapies as well as their implications for the management of patients with advanced/metastatic urothelial carcinoma.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Rationale for emerging targeted therapies for advanced/metastatic urothelial carcinoma
    • Available evidence for emerging targeted therapies for advanced/metastatic urothelial carcinoma
  • Demonstrate greater confidence in their ability to
    • Understand the clinical implications of the available evidence for emerging targeted therapies for the treatment of advanced/metastatic urothelial carcinoma


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  • Thomas Powles, MBBS, MRCP, MD

    Professor of Genitourinary Oncology
    Barts Cancer Institute
    Queen Mary University of London
    London, United Kingdom


    Disclosure: Thomas Powles, MBBS, MRCP, MD, has the following relevant financial relationships:
    Advisor or consultant for: Astellas; AstraZeneca; Bristol Myers Squibb; Eisai; Exelixis; Incyte; Ipsen; Johnson & Johnson; Merck; Merck Serono; Merck Sharpe & Dohme; Novartis; Pfizer; Roche; Seattle Genetics
    Grants for clinical research from: Astellas; AstraZeneca; Bristol Myers Squibb; Eisai; Exelixis; Ipsen; Johnson & Johnson; Merck; Merck Serono; Merck Sharpe & Dohme; Novartis; Pfizer; Roche; Seagen, Inc
    Other: Travel: AstraZeneca; Ipsen; Merck Sharpe & Dohme; Pfizer; Roche

  • Yohann Loriot, MD, PhD

    Department of Cancer Medicine
    Université Paris-Saclay
    Institut Gustave Roussy
    Villejuif, France


    Disclosure: Yohann Loriot, MD, PhD has the following relevant financial relationships:
    Advisor or consultant for: Astellas; AstraZeneca; Bristol Myers Squibb; Immunomedics; Janssen; Merck Kg; Merck Sharpe & Dohme; Pfizer; Roche; Seagen, Inc
    Grants for clinical research from: Celsius; Janssen; Merck Sharpe & Dohme; Sanofi

  • Jonathan Rosenberg, MD

    Medical Oncologist
    Chief, Genitourinary Medical Oncology Service
    Division of Solid Tumor Oncology
    Enno W. Ercklentz Chair
    Memorial Sloan Kettering Cancer Center
    New York, New York, United States


    Disclosure: Jonathan Rosenberg, MD, has the following relevant financial relationships:
    Advisor or consultant for: Astellas; BioClin; Boehringer Ingelheim; Bristol Myers Squibb; EMD Serono; Immunomedicas/Gilead; GlaxoSmithKline; Janssen; Lilly; Merck; Mirati Therapeutics; Pfizer; QED; Roche/Genentech; Seagen, Inc; Tyra Biosciences
    Speaker or a member of a speakers bureau for: EMD Serono
    Grants for clinical research from: Astellas; QED; Roche/Genentech; Seattle Genetics


  • Megan Cannon, PhD

    Medical Education Director, WebMD Global, LLC


    Disclosure: Megan Cannon, PhD, has disclosed no relevant financial relationships.

  • Ryan Blanchard, BS

    Scientific Content Manager, WebMD Global, LLC


    Disclosure: Ryan Blanchard, BS, has disclosed no relevant financial relationships.

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  • Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance


    Disclosure: Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP, has disclosed no relevant financial relationships.

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Latest Advances With Targeted Therapies for Advanced/Metastatic Urothelial Carcinoma: Evidence and Implications

Authors: Thomas Powles, MBBS, MRCP, MD; Yohann Loriot, MD, PhD; Jonathan Rosenberg, MDFaculty and Disclosures

CPD Released: 12/10/2021

Valid for credit through: 12/10/2022


Activity Transcript

Chapter 1

Thomas Powles, MBBS, MRCP, MD: Hello, I'm Tom Powles from Bart's Cancer Center in London in the UK. Today I'm going to talk about the current challenges for managing advanced urothelial cancer.

You can see from this slide here that there are a number of treatments, this algorithm shows us there are a number of treatments for urothelial cancer. If you go back 5 years or 10 years, chemotherapy was actually the only treatment for advanced urothelial cancer. The first issue is around this unmet need issue, and people have talked about carboplatin patients being this unmet need. Actually, I would argue the whole of urothelial cancer is an unmet need. The most recent data suggests the outcomes for gem/cis, gemcitabine cisplatin, gemcitabine carboplatin, are more similar to each other than different, and actually the survival is in the region between 12 and 15 months. That's actually much shorter than we'd like it to be. Certainly, shorter than the other cancers I treat.

And actually, although we've developed these immune therapies and they've certainly helped subsets, perhaps 20% of patients a great deal with long term durable remissions, the majority of patients are still dying of their cancers quite quickly. How are we going to address this? Well, you can see from this algorithm, the current standard of care is gem/cis gem/carbo, followed by maintenance avelumab, with level IA evidence. There is an option giving frontline immune therapy with atezolizumab or pembrolizumab. This has only got level III evidence, and actually's more risky. And the reason why that's the case is many patients can get frontline immune therapy, their cancers grow quickly, and many patients don't get the opportunity for second-line therapy.

What happens to those patients, and let's face it, it's still most patients, that progress after chemotherapy and immune therapy? Well, the first thing to say is we now have level IA evidence for enfortumab vedotin. This an antibody-drug conjugate targeting nectin-4. It's got a survival advantage versus what was previously standard chemotherapy. This is very exciting, and we're going to learn more about that today in our program. Also, sacituzumab govitecan is an antibody-drug conjugate. This also has activity. It's not a randomized trial, it's a single-arm study, however it has FDA approval, and we will also talk about that.

If we put the antibody-drug conjugates to one side, what other opportunities are there for our patients with platinum-refractory and immune-refractory disease? Well, there's targeted therapy, and Yohann Loriot is going to talk today in our program about that. The key targeted therapy is FGFR targeting those patients whose cancers have DNA alterations to FGFR, which is about 20% of patients. We can give erdafitinib with a 40% response rate in platinum refractory disease. We're going to learn more about that today. And of course, there are other targeted therapies as well in this area. Finally, Jonathan Rosenberg's going to talk about a combination of immune therapy and targeted therapy, immune therapy and antibody-drug conjugates, which we hope will move into the frontline space and replace chemotherapy altogether.

Please continue on to listen to the next section on the role of antibody-drug conjugates for advanced urothelial cancer.

Chapter 2

Thomas Powles, MBBS, MRCP, MD: Hi, I'm Tom Powles from Barts Cancer Institute in London in the UK. Today, I'm going to talk about the role of antibody-drug conjugates for advanced urothelial cancer.

I think there is clearly a need for new treatments in urothelial cancer. The issues we've had with chemotherapy and immune therapy have taken us so far. This new class of drug, which is specifically targeting cancer cells with an active payload, is a very new, attractive option, and has shown efficacy which is actually greater, in my opinion, than expected.

Of course, it has new challenges with toxicity issues, which we're going to talk about today. Enfortumab vedotin and sacituzumab govitecan will be covered, and I'll also talk about the clinical implications for treatment.

Enfortumab vedotin, on the left-hand side of this slide, you can see here targets nectin-4. Over 95% of urothelial cancers overexpress nectin-4. You can see here the processes of internalization and targeting with MMAE, which is the chemotherapy payload.

On the right-hand side of the slide, you can see sacituzumab govitecan. This has an SN-38 payload and targets tropTrop-2.

The linker molecule is key for both of these drugs. The linker molecule has to come undone to allow the payload to deliver. So, there are 3 parts to these molecules, and actually all 3 parts are crucial: 1 for targeting, 1 for allowing administration, and the third, clearly, the payload, is also very relevant.

The first trial I'm going to talk about is EV-301. EV-301 is a randomized phase 3 study. It compares enfortumab vedotin, at standard doses, with pre-selected chemotherapy. The chemotherapy consisted of docetaxel, paclitaxel, or vinflunine. These patients' cancers had progressed previously after both chemotherapy and immune therapy, making it a third-line trial, or, if patients had progressed after chemotherapy and maintenance avelumab, a second-line trial. Overall survival was the primary endpoint of the study.

Patients' demographics of the trial was well balanced. Here you can see a significant survival advantage for enfortumab vedotin: a 30% reduction in the risk of death. The curves go apart and they stay apart.

The progression-free survival advantage is also significantly better for enfortumab vedotin; the response rate of 40% is in line with the phase 2 data. Indeed, these data, which were very similar to the phase 2 data, really reinforce the activity of this agent.

My experience of the activity of the drug is that patients who have aggressive disease, we are able to get in rapid control of the disease within enfortumab vedotin, making it for some patients, a really big difference in not only cancer control, but also extending life.

The drug's associated with key adverse event profiles, 3 adverse events that need attention. It's associated with a rash, it can also cause peripheral neuropathy, and thirdly, it can be associated with hyperoglycemia. However, you can see here it didn't lead to more treatment discontinuations compared to chemotherapy, and the serious adverse event profile was similar to chemotherapy in terms of the percentages.

Therefore, overall, it's fair to say it has similar toxicity to previously used agents. However, the toxic profile is different to drugs being used in other studies, and this is a phase 2 study, for patients whose cancers have progressed after just immune therapy. This is essentially a second-line post-immune therapy study.

You can see here that there is 89 patients included, with a 52% response rate. 20% of patients had a confirmed complete response, and only 9% had progression of disease. Again, this data looks... I realize the numbers are modest, but it looks very provocative and active in this space, with overall survival within the region of 14 months. The adverse event profile, very similar to as I've said before.

Let's move to sacituzumab govitecan. As I said before, this is a drug which is targeting Trop-2 with SN-38 as the payload, so completely distinct from enfortumab vedotin. And this is a phase 2 study for patients whose cancers have progressed after platinum-based chemotherapy,

113 patients, response rates of 27% progression-free survival of 5 months, and OS of 11 months. Overall, again, this drug looks active. We can't make cross-trial comparisons with such small numbers. We shouldn't do that anyway, but particularly in this setting. The adverse event profile, well, this is different. So, this is associated with more SN-38-type adverse events, with hematological toxicity including neutropenia, GI toxicity including diarrhea, and general toxicity including fatigue.

This is the TROPiCS-04 trial, which we're doing at our centers, including many other centers, and you can see in this trial, we are comparing sacituzumab with standard chemotherapy. The trial design is actually very similar to the 301 study, so patients whose cancers have progressed after immune checkpoint inhibitors and chemotherapy, either sacituzumab govitecan or chemotherapy in a 1-to-1 randomization.

The clinical implications of the data I presented today are really profound, because for the first time, we have something genuinely active to give patients after chemotherapy and immune therapy. We all know those patients that we have that have done well with chemotherapy, initial responses have been okay with immune therapy, but the cancers are progressing. And now we have enfortumab vedotin with level IA evidence to support these patients with a 40% response rate; remember, historically, response rates in the region of 10% for standard chemotherapy; but also, a 30% improvement in survival.

And as I said before, other drugs are coming through in this space, including sacituzumab govitecan, which is FDA-approved, and we have randomized trials ongoing, which we hope will also be positive. One of the exciting questions will be: do these drugs have cross-resistance or can we sequence them? One of the important questions is about education and training for the community regarding the adverse events of these drugs, which are distinct from chemotherapy.

Please continue to listen to the next section of our program on the role of FGFR inhibitors for advanced urothelial cancer.

Chapter 3

Yohann Loriot, MD, PhD: Hi everyone. I'm happy to discuss today FGFR inhibitors for advanced urothelial carcinoma at this digital webinar. I'm Dr Loriot. I'm a medical oncologist at Gustave Roussy in Villejuif, Paris.

So FGF receptor alterations are frequent in advanced urothelial carcinoma. FGF receptors are tyrosine kinase receptors, and 4 FGFR receptors have been identified, and 18 ligands which act as paracrine or autocrine factors. FGF receptors are activated upon FGF binding. And upon dimerization, FGF receptors activate downstream signaling pathways such as RAS, MAP kinase, and PI3 kinase pathways.

A lot of FGF alterations have been described and the most relevant in advanced urothelial carcinoma are mutations and fusions. The most frequent mutations are located in the FGF binding region like S249C mutations. FGFR Other mutations have been found in the transmembrane helix and less frequently in the kinase domain. So globally, FGFR3 mutations are found in 15% of MIBC and up to 50% in non-muscle invasive bladder cancer. On top of mutations, there are also some fusions that affect either FGFR2 or FGFR3 genes. And overall, they are quite rare and found in 2% to 3% of MIBC.

So, what are the available clinical evidence for FGFR inhibitors? Historically, non-selective FGFR inhibitors have been developed, but the activity of this component was low. The last one, derazantinib, is more specific, but targets also other enzymes and is currently investigated in early-phase clinical trials.

More selective FGFR inhibitors have been developed. And you can see the 2 that are approved in oncology, so erdafitinib in urothelial cancer and pemigatinib in cholangiocarcinoma.

The FGF receptor inhibitors are currently investigated in all disease stages. And of course in late-stage setting in pretreated metastatic patients, but also in perioperative setting and also in earlier stage in non-muscle invasive bladder cancer.

So what is the efficacy? On this slide you can see the response rate. The response rate in patients with FGFR2,3 alterations and treated with FGFR inhibitors that have been generated by phase 1 and phase 2 trials. We don't have so many data from phase 3 trials so far. And what we see is that the responses are observed mainly in patients with FGFR2 or FGFR3 fusions and FGFR3 mutations. Other FGFR alterations, for example, FGFR1 amplification, FGF amplifications are not associated with good response.

Erdafitinib is the only one approved in urothelial cancer. In the phase 2 trial, the BLC2001 study in , heavily pretreated metastatic patients with specific FGFR3 or FGFR2 gene alterations were treated with erdafitinib. So dose regimen was quite original since the drug was given continuously with dose titration based on the phosphate level assessed early during the first cycle. Indeed, phosphate level was shown to be associated with better response and considered as a biomarker of activity of the drug.

So overall response was 40% and median PFS around 6 months, so better than the expected activity of chemotherapy used in this setting. So, based on this data erdafitinib was approved by FDA 2 years ago.

So what are the next steps? First, we have to fully demonstrate the efficacy of this drug. And a couple of phase 3 trials are ongoing. The FORT-1 trial was a phase 2/3 trial which compares rogaratinib and chemotherapy in patients with advanced urothelial carcinoma and FGFR3 overexpression. FGFR1/2/3 mRNA was tested by in situ hybridization of archival tissue. The patients were assigned to rogaratinib or to chemotherapy. And actually the trial stopped early. Response rate was around 20% in both arms. And median PFS was not different between the 2 arms.

In another phase 2 3 trial, the THOR trial is ongoing comparing erdafitinib to standard of care. The patients are selected based on RT-PCR to detect several prespecifying mutations or fusions affecting FGFR2 or FGFR3 genes. The patients are treated with erdafitinib or either pembrolizumab or chemotherapy based on the prior treatment that the patients have received. Overall survival is the primary endpoint.

So what is the safety profile of this drug? As we order target therapy, patients may develop toxicities. FGFR-related adverse events affect mainly the eye with the risk of CSR, hyperphosphatemia, dry skin, and nail toxicity, and less frequently, diarrhea or hepatic cytolysis.

Usually, the FGFR inhibitors are well-tolerated and most common adverse events are grade 1, grade 2. But the patient needs careful examinations with regard to hand and foot syndrome, nail toxicity, and CSR. So, education, training, and multidisciplinary collaboration are of utmost importance.

What are the next steps? Of course, we have to fully demonstrate the efficacy of this drug. This is a goal of THOR. So enroll your patient in a clinical trial. Then, this drug should be assessed in earlier stage in first-line metastasis setting or even earlier in perioperative setting and in non-muscle invasive bladder cancer. So lastly, some combination and especially with immunotherapy should be tested.

So here, an overview of the clinical development of FGFR inhibitors as you can see. Almost all settings are covered by the development of FGFR inhibitors. So international and national guidelines have integrated this class of drug. Here is an example with the ESMO guidelines. Erdafitinib is an option in platinum- and immune checkpoint inhibitors, -refractory tumors. NCCN guidelines also indicate that erdafitinib is an option in metastasis setting for patients with prespecified gene alterations.

The question is when should we test the tumors? So usually, FGFR3 mutations and fusions occur early during disease evolution. So it means that we should test the tumor as early as possible when the patient is diagnosed with metastasis. If there is a mutation, you can enroll patients in a clinical trial in first-line. Or you can treat the patient with standard of care, so chemotherapy, and switch the patient to erdafitidnib if there is any disease progression on chemotherapy and/or immunotherapy.

How can we test the tumors? The easier way is to collect the part of a archival tissue and to test a tumor. But as you know, sometimes it takes a long time to collect this sample. So, what we can do is to test cell-free DNA. In our experience, for example, there is a good concordance between cell-free DNA and tissue testing.

So as a conclusion, FGFR2 and FGFR3 alterations are common in advanced urothelial carcinoma. The most oncogenic alterations are mutations and fusions and affect FGFR3 gene. Only 1 FGFR inhibitor is approved by FDA so far, erdafitinib, which is approved for pretreated metastatic urothelial carcinoma with prespecified DNA alterations. And there is a lot of clinical trials ongoing in first-line and in pretreated patients like the THOR trial.

Thank you again, and now please continue on to listen to the next section on combination strategies for targeted therapy with immunotherapy. Thank you.

Chapter 4

Jonathan Rosenberg, MD: Hello. My name is Dr Jonathan Rosenberg from Memorial Sloan Kettering Cancer Center in New York in the United States. Today, I'm going to talk to you about combining targeted therapies with immunotherapies, where we are now and where we're going. I'm going to start by talking about the rationale for combining targeted therapies with immunotherapies, and review the data from several clinical trials that are either ongoing or have been reported, and what the implications may be of these in the future.

The first study that I will be talking about today is EV-103. These are the first-line cohorts of enfortumab vedotin and pembrolizumab in combination therapy. The recommended phase 2 dose data was reported in 45 patients. And these data show that the response rate was 73% in this patient population, not really depending dramatically on PD-L1 status in the combination therapy, that 93% of patients had tumor reductions in this modest size cohort of data. And these data have led to the FDA breakthrough therapy designation for EV and pembrolizumab. We see here on the spider plot that the majority of responses happen very quickly. The median time to response was 2.1 months, and almost 90% of responses were observed at the first tumor assessment. And so responses are rapid and many of them appear durable as we see patients continuing on therapy, even beyond 2 years. The progression-free survival for EV and pembrolizumab in this study was 12.3 months.

Then, when we put it in context, this cisplatin-ineligible patient population when treated with carboplatin, we expect a progression-free survival of 6 to 9 months, rather than over 12 months. In addition, the observed overall survival in the cisplatin-ineligible population was 26.1 months. Again, double what we might necessarily expect from historical studies of carboplatin-based chemotherapy. And so, this represents a potential game changer in the future for patients with cisplatin-ineligible advanced urothelial cancer.

There are currently 2 clinical trials that are ongoing that are randomizing patients with enfortumab vedotin and pembrolizumab. The first one is cohort K of EV-103. This is randomizing patients to single agent therapy with enfortumab compared to combination therapy, enfortumab vedotin/ pembrolizumab. And this trial may result in an accelerated approval for the combination therapy in cisplatin-ineligible patients.

In addition, there's a randomized phase 3 trial of enfortumab vedotin and pembrolizumab compared to gemcitabine and platinum chemotherapy. Patients are randomized 1 to 1 to either gemcitabine and cisplatin or gemcitabine and carboplatin or enfortumab vedotin and pembrolizumab. We look forward to the results of these trials as these are very likely to be practice changing in the future if the results of the phase 1b/2 study hold up.

Sacituzumab govitecan is another antibody-drug conjugate that's approved for use in advanced refractory bladder cancer.

Here are the data from TROPHY-U-01 cohort 1 testing sacituzumab govitecan in patients with metastatic platinum- and checkpoint-refractory disease. And we see that the response rate is 27% and that 5% of patients had complete responses and the median duration of response was 7.2 months. These are the data that led to the accelerated approval of sacituzumab in urothelial cancer.

There is a combination trial ongoing of sacituzumab and pembrolizumab in checkpoint-naive patients who've progressed after platinum therapies of the combination of sacituzumab and pembrolizumab as noted here. Accrual is ongoing and we eagerly look forward to the results of this trial.

FGFR3 mutations are present in a minority of advanced bladder cancer patients, about 15% to 20%. There is conflicting data whether FGFR3 mutations are associated with a lower response rate to immune checkpoint blockade. Some clinical trials suggest yes, others suggest no. It is possible and we think that FGFR inhibition might lead to priming of the tumor immune microenvironment, setting up the tumor for a better response to immune checkpoint blockade, providing the rationale for the combination trials of immunotherapy and FGFR3 inhibitors that have been undertaken.

And there are 2 trials that have reported data thus far, looking at the combination therapy of FGFR3 inhibitor and an immune checkpoint inhibitor.

The one reported recently at ESMO by Dr Powles was the randomized phase 2 NORSE study randomizing patients to erdafitinib or erdafitinib plus cetrelimab. That is an investigational immune checkpoint inhibitor, not yet approved. The eligibility criteria were patients with mutations that are activating in FGFR3 and who are ineligible for cisplatin-based chemotherapy. They were randomized to monotherapy with erdafitinib or erdafitinib plus the checkpoint inhibitor.

The number of patients in the trial were relatively small in the interim analysis that was reported and for efficacy, 18 patients with erdafitinib and 19 patients with cetrelimab. And so, keep that in mind when you're seeing the data. However, these data are impressive. The response rate for erdafitinib monotherapy in untreated patients was 33%, but in combination with a checkpoint inhibitor, that response rate was 68%, including 21% of patients with complete responses. And many of those responses are still ongoing.

We see on the spider plots that the responses with the combination therapy appear to be deeper, perhaps more prolonged. And so, we look forward to mature data from this clinical trial and completion of accrual of the combination randomized phase 2 study here.

FORT-2 is a study of rogaratinib, which is a pan-FGFR3 inhibitor, and atezolizumab. And we saw similar results with a 58% response rate of the combination. This was a single-arm study. The notable difference between rogaratinib and erdafitinib selection strategies is that rogaratinib has been developed with a companion diagnostic, looking at RNA overexpression of FGFR3 while erdafitinib focuses on mutations and fusions. But we see this high response rate in patients in a predominantly low PD-L1 population suggesting that there may be some real effect of FGFR inhibition in this patient population in combination with immunotherapy.

Thank you for listening. We are in an exciting time in advanced bladder cancer, and we're seeing combination therapies with response rates that we have not seen previously and I hope that these translate into true clinical benefits for our patients in randomized trials.

Please continue to listen to the final session. Thank you very much.

Chapter 5

Thomas Powles, MBBS, MRCP, MD: Hi I'm Tom Powles from Barts Cancer Center in London. In this segment, I'm going to summarize what you've heard so far from our program.

Initially, I presented some information around the unmet need for these patients. Tragically, the vast majority of these patients with metastatic urothelial cancer succumb to their disease. And actually, chemotherapy and immune therapy for the majority of patients only takes us so far.

We initially went on and talked about the role of antibody-drug conjugates. I focused on enfortumab vedotin, which has level IA evidence for patients whose cancers have progressed after chemotherapy and immune therapy. We talked about a high response rate of 40%. We talked about a 30% reduction in the risk of death for that drug. We then went on and talked about the phase 2 data for sacituzumab govitecan. This antibody-drug conjugate has different targets and a different payload, different drug, different activity. And we talked about some of the ongoing trials for sacituzumab govitecan, which is not quite as advanced in its development as enfortumab vedotin.

Yohann Loriot then came on and talked about FGFR inhibitors. He focused predominantly on erdafitinib, which has FDA approval. He also described a 40% response rate in individuals whose cancers have FGFR DNA alterations. He talked about the toxicity profile of the drug, and he also talked about ongoing trials, including the THOR study, which potentially would change global practice outside the United States of America.

Jonathan Rosenberg came on and talked about what was perhaps the most exciting chapter for the future, which is the combination of these drugs with particularly immune checkpoint inhibitors. He talked about studies, which could change practice, including the EV-302 trial, which was pembrolizumab and enfortumab vedotin versus frontline chemotherapy. The phase 2 data for that combination looks so promising that we hope we can replace chemotherapy altogether in the not too distant future.

All 3 of us talked about some of the challenges around the drugs and this includes issues around toxicity. We're going to have to learn how to use these drugs better from a global perspective, because although the drugs aren't necessarily more toxic or less toxic than immune therapy or chemotherapy, each of them has different toxicity profiles, including things like neuropathy or nail toxicity, which requires attention.

I'd like to thank you very much for participating in this activity. I hope you've enjoyed it. I hope we've explained to you how quickly we think things are moving in this cancer. Please continue on to answer the questions that follow to complete the evaluation.

This program was presented by Medscape Education Global.

This transcript has been edited for style and clarity.

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