Tag Archive for: Padcev

Bladder Cancer Breakthroughs: Immunotherapy and Preservation Strategies

Bladder cancer treatment has some new options for patient care. Expert Dr. Shaakir Hasan from Beth Israel Lahey Health shares an overview of the latest treatment options, how they work against bladder cancer, access to the treatments, and proactive patient advice to help ensure optimal care. 

[ACT]IVATION TIP

“…don’t kind of settle for just if they just give you one approach and that’s it, they don’t mention anything else. You’ve got to question that a little bit. But the vast majority of providers will at least tell you…acknowledge that there are other options out there.”

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When Is Immunotherapy Recommended in Bladder Cancer?


Transcript:

Lisa Hatfield:

Dr. Hasan, can you provide an overview of the latest treatment options for advanced bladder cancer, and in particular, the role of immunotherapy and how it works to treat bladder cancer?

Dr. Shaakir Hasan:

Absolutely. So this is a really exciting time in bladder cancer treatment because for a couple reasons. I’d say there are two kind of main frontiers. I’ll address the immunotherapy first. So for the longest time, we were treating bladder cancer, particularly metastatic bladder cancer, i.e., Incurable bladder cancer with platinum-based chemotherapy. So chemotherapy is cytotoxic, meaning it goes, and it’s all throughout your body. It’s systemic, and it kind of kills everything. It attacks everything. Tumor cells are more susceptible to this type of treatment because they have high cell turnover, and as they turn over, they’re more exposed. Your DNA is more exposed to these mechanisms of cell kill. And so they’re differentially affected, but it still does a number on the rest of the healthy tissue in your body. Immunotherapy is newer, and it’s a type of treatment that inhibits the inhibition of your own immune system.

In other words, it helps the immune system work better. And that’s important, because the immune system is one of the main tools in fighting cancer. It does recognize these cancerous cells as not necessarily foreign, but abnormal cells that shouldn’t be there. And so it does help your body attack those cells. And when it does that, it’s more selective than the cytotoxic classic chemotherapy that we use. And so we’re adopting this immunotherapy in more and more cancers. Bladder is one of them, and just, I want to say in the past six months, they had a really big study that compared classic platinum-based therapy to a combination of pembrolizumab (Keytruda) and enfortumab vedotin-ejfv (Padcev), which it’s called an antibody drug conjugate, an ADC. It’s another mechanism that it works in conjunction with immunotherapy to kind of better isolate these tumor cells to destroy them.

And that showed a dramatic increase in survival and disease control compared to classic chemotherapy. So, that’s doing really well, and we hope to see that more earlier in more curable stages of disease as well. So that’s an exciting frontier. The other aspect I would say is we’re seeing more and more bladder preservation. Now, I’m a radiation oncologist. I might be biased in this topic, but historically we’ve always treated curable bladder cancer with a combination of chemotherapy and surgery. So you remove the bladder in its entirety, you remove the cancer with it, and then you give systemic therapy to prevent any stragglers, we’ll call them cancer cells that are just left behind.

And this has been effective, but of course you lose your bladder. And so this is some at the end of the day, if you can preserve it, if you can preserve the organs you were born with, you want to do that. And if you, instead of doing a cystectomy, which is removal of the bladder, if you do a combination of chemotherapy and radiotherapy, and probably in the future immunotherapy altogether, you can have the same chances of cure, same chances of survival, but preserve the bladder. So we’re seeing that more and more these days.

Lisa Hatfield:

Okay, thank you. I do have a follow-up question to that also. So if a patient’s watching this maybe lives in a smaller community, doesn’t live near a big academic center, are these immunotherapies in clinical trials only, or are they being used at more local centers? And then also for things like radiotherapy how about that type of therapy also, can they access that at their local cancer center?

Dr. Shaakir Hasan:

Great question. So immunotherapy at this point really should be everywhere. It really really should be everywhere. It should not be difficult to access, whether you’re in a rural community or in a big level four academic center. Radiation can be more variable, not because of the access, because frankly, you should be able to find a radiation oncology clinic within I don’t know, a half-hour of anywhere that you are in the country there are enough of those clinics in the country. However, it just varies place to place as to the types of treatments that they’re comfortable doing. And also as an institution it is a multimodality approach. You have to have a urologist to buy in. You have to have the medical oncologist to buy in and the radiation oncologist to buy in. And that can just change institution to institution.

In either scenario, when it comes to an [ACT]IVATION tip, I would say do not settle for what’s offered to you if you know that these other options are available. So, you do a simple Google and you find out what are the treatment options available, and then you just mention them to your local oncologist. And the vast majority of them, whether they provide them or not, will tell you, oh yeah, that is an option. We don’t do that here, but please check out these other places. And, so don’t kind of settle for just if they just give you one approach and that’s it, they don’t mention anything else. You’ve got to question that a little bit. But the vast majority of providers will at least tell you…acknowledge that there are other options out there.

Expert Update: Bladder Cancer Treatment & Research News

Expert Update: Bladder Cancer Treatment & Research News  from Patient Empowerment Network on Vimeo.

Dr. Fern Anari reviews highlights from the ASCO 2022 meeting and shares her expert perspective on the future of bladder cancer treatment.

Dr. Fern M. Anari is a genitourinary medical oncologist and assistant professor in the department of hematology/oncology at Fox Chase Cancer Center. Learn more about Dr. Anari, here.

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Transcript:

Katherine Banwell:

Dr. Anari, cancer researchers recently came together for the 2022 ASCO meeting. Were there any highlights from that meeting that bladder cancer patients should know about?  

Dr. Anari:

Yes. So, our annual meetings are always a really exciting time to learn about and share the results of really cutting-edge research that’s been going on. And this year at ASCO 2022, I think there were several standout studies for various stages of bladder cancer. 

So, in patients with localized bladder cancer, again, similarly to what we discussed with immunotherapy and what we call BCG unresponsive bladder cancer, they looked at combining BCG with another new drug. And what they found is that the cancer shrunk down completely in over two-thirds of cases. 

And those responses tend to last over two years of follow-up. The drug was shown to be safe and tolerable. So, I think that’s a really exciting potential future treatment for people. There was another study that looked at a targeted treatment called enfortumab vedotin, which is typically used in the metastatic setting after someone’s received chemotherapy and/or immunotherapy. They looked at using that before surgery in localized muscle-invasive bladder cancer. 

The reason it’s important to look at drugs like this is because the standard of care right now is to give cisplatin-based chemotherapy before surgery to remove the bladder.  

But not everyone is eligible to get that cisplatin drug for various reasons. So, the current standard of care is to just go straight to surgery. But we know that by giving some form of a chemotherapy before, that helps increase cure rates. 

And what they actually found in this study looking at enfortumab vedotin is that they were able to shrink down cancer completely, meaning at the time of surgery there was no cancer left in the bladder 36% of the time, which is actually on par with our standard of care treatment that we use today.  

So, I think this also shows a lot of promise in patients who historically would need to go straight to surgery without any preoperative treatment. And then, lastly, HER2 is a type of targeted therapy as well that’s most commonly known in the breast cancer treatment world. But it’s also been looked at in bladder cancer.  

And there’s a new drug that’s being studied that really strongly targets HER2, which is expressed on some bladder cancer cells. So, they’re looking at this new drug in combination with immunotherapy, which is already approved in bladder cancer. And, again, I think this is another really promising combination for patients who’ve already received other treatments for their bladder cancer.   

Katherine Banwell:

It sounds like a lot of progress is being made in the field.  What are you excited about when it comes to bladder cancer research?   

Dr. Anari:

I think what excites me the most is being able to offer patients both the standard treatment options where, really, the clinical trials of yesterday are our standard treatments today. So, I’m excited to be able to offer them the standard treatment but also give them the background of why that’s approved and why we use it but also give them the hope that we have these really promising drugs.  

And, luckily, at our cancer center, we have access to a lot of these before they’re approved by the FDA. So, it’s really exciting to be able to offer this cutting-edge research in the form of treatments to our patients. 

Emerging Approaches in Bladder Cancer Treatment

Emerging Approaches in Bladder Cancer Treatment from Patient Empowerment Network on Vimeo.

Dr. Shilpa Gupta of the Cleveland Clinic shares a promising update in bladder cancer treatment and research, including the benefits of patient participation in clinical trials. 

Dr. Shilpa Gupta is the Director of the Genitourinary Medical Oncology at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. Dr. Gupta’s research interests are novel drug development and understanding biomarkers of response and resistance to therapies in bladder cancer. Learn more about Dr. Gupta, here.

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Transcript:

Katherine:                  

So, Dr. Gupta, are there emerging approaches for treating bladder cancer that patients should know about?

Dr. Gupta:                  

Yes, absolutely. I would say that the field is so rife with so many different treatment approaches and ways to offer more personalized medicine. We know, for example chemotherapy followed by surgery has been the gold standard, but we have seen data that there are certain genes in some patients’ tumors which may predict how well they will respond and potentially we could avoid a life-changing surgery like cystectomy.

And we have trials with immunotherapy adding to chemotherapy in bladder preservation approaches along with radiation. So, these are some of the new work that’s been done. Approaches to intensify the effect of BCG in newly diagnosed non-muscle invasive bladder cancer patients are also ongoing. Then, in the metastatic setting, we have so many treatment options that have become approved in the last couple of years, now the goal is, well, how to sequence the therapies best for the patient and whether in the front-line therapy we can actually get rid of chemotherapy.

Some of these antibody drug conjugates and immunotherapy combinations are proving to be very effective and the hope is that one day patients may not need chemotherapy because we have chemo-sparing regimens. So, there’s a lot going on and I think the progress has been tremendous in the past few years.                                            

Katherine:                  

Some patients may be fearful when it comes to clinical trials. So, what would you say to someone who might be hesitant to consider participating in one? 

Dr. Gupta:                  

I would say there’s a lot of misconceptions out there that going on a trial is like being a guinea pig or you get a placebo. For the most part, patients are getting active drugs whenever possible. The only time where we have placebo-controlled trials is if, for that particular setting, there is no approved treatment. But I think patients should get all the information from their doctors and the study teams about the pros and cons.

Many times, it’s about – you could do the study because the patients meet the criteria and are fit to do it and if they wait for later, they may not be eligible anymore for whatever reasons.

I always put it this way, that standard of care therapies will still be available, but studies are sometimes with a tight window and tight criteria. So, I think patients should know that all these studies that are out there are very ethical and use the best possible control arm. So that even if they don’t get that experimental drug, they still get what is the standard of care unless it is something really being compared to nothing.    

Current Treatment Approaches for Bladder Cancer

Current Treatment Approaches for Bladder Cancer from Patient Empowerment Network on Vimeo.

Dr. Shilpa Gupta provides an overview of available bladder cancer treatment approaches and discusses the factors that impact therapy decisions.

Dr. Shilpa Gupta is the Director of the Genitourinary Medical Oncology at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic. Dr. Gupta’s research interests are novel drug development and understanding biomarkers of response and resistance to therapies in bladder cancer. Learn more about Dr. Gupta, here.

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Transcript:

Katherine:                  

You’ve touched upon treatment options but let’s walk through the treatment approaches for bladder cancer and who they might be right for, and I’d like to start with surgery. Who would be a good candidate for surgery?

Dr. Gupta:                  

I think patients who are otherwise fit, that is, they have good performance status, don’t have a lot of cardiac or other comorbidities, are not very obese, and of course have to be fit for any major procedure are usually considered good surgical candidates. But, as far as – In terms of staging, the patients with stage I, if BCG does not work in them or immunotherapy doesn’t work, they are recommended surgery if they are good candidates.

If they are not good candidates, we then – our role as medical oncologists is to offer other systemic therapies. As far as stage II cancer is concerned, the gold standard has been chemotherapy, followed by surgery but that’s the gold standard.

It may not apply for every patient. Depending on how fit patients are. Are they – we don’t usually just go by their chronological age but how fit they are? What are their comorbidities? If surgery is going to be a big burden for them moving forward, then we do talk about radiation and chemotherapy and other bladder preservation approaches.

Katherine:                  

What about immunotherapy and targeted therapies? Who would you use those on?

Dr. Gupta:                  

Well, since the advent of immunotherapies back in 2016 they’ve really – we’ve made a lot of progress and changed the way treat bladder cancer and the overall survival has improved by leaps and bounds with all these drugs.

Immunotherapy now plays a role in different stages. It is approved for superficial or non-muscle invasive bladder cancer if, let’s say, BCG doesn’t work. In muscle invasive disease we have along with others shown that immunotherapy is safe and effective, although it is not yet FDA approved, so there is a lot of clinical trials going on to prove its superiority in combination and by itself.                                   

And, in metastatic disease or locally advanced disease immunotherapy plays a huge role for patients who have either disease recurrence after chemotherapy or are not good candidates for any chemotherapy.

I would say that immunotherapy is a very big – plays a very big role in the treatment. Unfortunately, not everybody responds to immunotherapy only about 20 to 25 percent of patients do.

 That’s why we have these other novel therapies that have been coming through, like antibody drug conjugates, namely enfortumab vedotin, sacituzumab govitecan, and targeted therapy in the form of an FGFR inhibitor was the first targeted therapy that was approved a couple of years ago for patients who have a mutation in their tumors.

That’s really personalized medicine for those patients.

Katherine:                  

Right. What about biomarker testing? Does the presence of certain biomarkers impact certain treatment options?

Dr. Gupta:                  

That’s a great question and we’re all striving to find the perfect biomarker in bladder cancer. In the past we thought that expression of PD-L1 in the tumor cells and immune cells is a marker of how well the immunotherapy will work, but we have learned over the past couple of years that biomarker has turned out to be quite useless.

We don’t really need that to guide our treatment. We’re still depending on clinical biomarkers for immunotherapy use or chemotherapy use. I would say that the biomarker question is still being looked at and eventually I would say it’s not going to be one biomarker, but a composite of several different biomarkers that we will be able to use comprehensively.