Transcript of I Can’t Get Chemotherapy to Treat My Bladder Cancer – Now What? with Dr. Guru Sonpavde

October 26, 2021

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Voice over:

This is Bladder Cancer Matters, the podcast for bladder cancer patients, caregivers, advocates and medical and research professionals. It’s brought to you by the Bladder Cancer Advocacy Network, otherwise known as BCAN. BCAN works to increase public awareness about bladder cancer, advances bladder cancer research and provides educational and support services for bladder cancer patients and their loved ones. To learn more, please visit bcan.org

Rick Bangs:

Hi, I’m Rick Bangs the host of Bladder Cancer Matters, a podcast for, by and about the bladder cancer community. I’m also a survivor of muscle invasive bladder cancer, the proud owner of a 2006 model of the year neobladder and a patient advocate supporting cancer research at the Bladder Cancer Advocacy Network, or as many call it, BCAN, producers of this podcast. This podcast is sponsored by Merck.

Rick Bangs:

I’m excited to have Dr. Guru Sonpavde bladder cancer director at the Dana-Farber Cancer Institute as my guest today. At Dana-Farber he leads multiple cutting edge clinical trials studying novel immunotherapy and targeted drugs to cure bladder cancer. He is also the national or international principal investigator of multiple clinical trials of bladder cancer patients, additionally, he is a member of the BCAN Scientific Advisory Board. Dr. Sonpavde, I am so pleased to have you here today to talk about a challenge facing many of our bladder cancer survivors, knowing that chemotherapy is the recommended treatment, but finding out that it is not an option available to them.

Dr. Guru Sonpavde:

Thank you Rick. I’m really excited to be on this podcast and thank you for the invitation. I agree that there are many patients who are not eligible for chemotherapy that do have bladder cancer. So, I think that in this situation that we have other options, thankfully, in the current day and age we have in patients with metastatic disease who need some form of therapy. Immunotherapy now approved couple of immunotherapy drugs, atezolizumab and pembrolizumab are approved in certain situations where patients are not eligible for cisplatin or not eligible for any chemotherapy where we can opt for these agents in specific situations.

Rick Bangs:

So let’s start with some basic understanding of chemotherapy to build on what you were just saying. We know that chemotherapy is often the most effective weapon available to somebody diagnosed with cancer and that’s true across the cancers, not just in bladder cancer. So chemotherapy is not just one thing is it, there are different types of chemotherapy, right?

Dr. Guru Sonpavde:

That’s right, Rick. There is a misconception out there that all chemotherapy is the same, there are multiple chemotherapy drugs and they all work in different ways. Chemotherapy has been around for a while now, at least about 50 years. As you know, they first came out in the realm of hematologic cancers, leukemias, lymphomas and we have been using chemotherapy, of course, for many of the so-called solid tumors like lung cancer, breast cancer, of course also bladder cancer. So the evolution of chemotherapy in bladder cancer is that we always knew that drugs like cisplatin, methotrexate, doxorubicin these are different chemotherapy drugs that work in different ways to slow down cell division, the division of cells that are rapidly dividing and growing yet it attacks them at the point of the cell division of the DNA apparatus around it.

Dr. Guru Sonpavde:

And so, some of these drugs were combined together to make a combination chemotherapy regimen, this happened back in the 90s with a regimen called MVAC. With that included four chemotherapy drugs, methotrexate, vinblastine, A is for adriamycin which is the trade name but the drug name is doxorubicin, and the C stands for cisplatin. So this four-drug chemotherapy regimen was found to improve survival, the length of life compared to just giving cisplatin alone. This led to the MVAC regimen coming as the new standard of care back in the 90s, early 2000s based on this data.

Dr. Guru Sonpavde:

So following that, you had a chemotherapy regimen called GC, gemcitabine plus cisplatin, which appeared to be more tolerable, less toxic. It’s been compared with the MVAC regimen in a head-to-head phase three trial in metastatic urothelial bladder cancer and it also had upper tract urothelial cancer patients in it that had metastatic disease. And in these group of patients, the GC regimen and the MVAC regimen showed similar survival, similar response rate and the GC regimen was less toxic, less side effects. So really, in the community the GC regimen has been favored based on this regimen.

Dr. Guru Sonpavde:

Yet another way of giving MVAC is give it in a dose-dense fashion, that is giving it every two weeks instead of every four weeks, which needs what we call growth factor support drugs like neupogen, neulasta, they boost the immune system, the neutrophil white blood cells to prevent infections. So along with this growth factor support MVAC can be done in a dose-dense fashion every two weeks, which has some benefits in addition to finishing the chemotherapy regiment quickly, the four to six cycles that you’re planning. There might actually be less infection risk than even the standard MVAC regimen.

Dr. Guru Sonpavde:

So these are all the chemotherapy regimens we have in the first line setting, we have late salvage chemotherapy approved for patients where the cancer is growing and these are moved down the line because of the advent of immunotherapy drugs and other new classes of drugs like antibody-drug conjugates. But these late chemotherapy drugs now include drugs like docetaxel, paclitaxel and in Europe there’s also a drug called vinflunine which has been used and is approved for late salvage chemotherapy.

Rick Bangs:

So cisplatin is a platinum chemo, right?

Dr. Guru Sonpavde:

Right.

Rick Bangs:

And the docetaxel, paclitaxel are those platinum or are those something else?

Dr. Guru Sonpavde:

Those are not platinum, those drugs work in a different way. They are the class of drugs called taxanes, so they work on the tubulins which are involved in cell division so it’s not the DNA directly. So indirectly all of these chemotherapy drugs will prevent cell division, either by attacking the DNA or the cell replicating machinery which includes the tubulin which is wrapped all around the DNA. In fact, the DNA wraps around it, so these structures help the cells divide.

Rick Bangs:

For a lot of patients, I think the recommendation is typically to go with the platinum chemo versus some of the other alternatives. So without getting to technical, do we know why the cancer responses better to the platinum chemos?

Dr. Guru Sonpavde:

That’s a good question Rick, we have been struggling to find a biomarker for platinum. It is thought that cancer cells that have a defect in DNA damage repair, so the cells cannot repair themselves quickly, is where the platinums work better because the damage cause by platinum is unable to be repaired by the cells. And so, people have looked at things like mutations in DNA damage repairing, enzymes in the tumor cell far predicting response to platinum based on the hypothesis that tumor cells that have these mutations, i.e. that cannot repair damage, should be more sensitive to platinum.

Dr. Guru Sonpavde:

So that is an easy, simplistic way of looking at it but I think that we have a long way to go actually, believe it or not, to tell why exactly tumor A is more responsive to platinum but tumor B is not. But, in general, the more rapidly diving tumors with DNA damage repair defects tend to be little more sensitive to platinum.

Rick Bangs:

And that’s true not just in bladder cancer, right? That would be true in other cancers so what don’t know in bladder cancer is also what we don’t know in other cancers.

Dr. Guru Sonpavde:

You are exactly right, this is also something we don’t know. Unfortunately, studies have tried to look at this DNA damage, repair, defect for predicting response to platinum in lung cancer, and actually they could not validate it. And in bladder there is similar interesting data to show that DNA damage, repair or defects in the tumor might make the cells more sensitive but they were not quite there yet in terms of using it in the clinic, but there is some interesting data to suggest that.

Rick Bangs:

And then, some patients would get something called carboplatin. So carboplatin is also a platinum drug but it’s more tolerable, what’s the difference between carboplatin and dose-dense MVAC which includes cisplatin and the gemcitabine cisplatin combination? What makes carboplatin different and preferred in some cases?

Dr. Guru Sonpavde:

So carboplatin is a kinder, gentler platinum. They made structural changes in the chemistry of the platinum so that carboplatin is a less toxic platinum, less kidney toxicity, less nerve toxicity or neurotoxicity. So this is really an agent we have used commonly in patients who are not eligible for cisplatin. It does seem less active than cisplatin which is why we prefer to use cisplatin whenever possible, but some patients are not eligible for cisplatin because of either poor kidney function, poor performance status which is medical lingo for poor physical activity of the patient. And also, other illnesses like congestive heart failure, peripheral neuropathy, severe hearing loss might all make you somewhat ineligible for cisplatin given the toxicities of cisplatin on all of these organs. So in those situations we use carboplatin-based chemotherapy.

Rick Bangs:

Okay. So you use the term less active. I would translate that, and correct me if I’m wrong, less active means that it is less effective in combating my cancer.

Dr. Guru Sonpavde:

You are exactly right, Rick. When you look at data across trials, when you look at the combination of carboplatin plus gemcitabine and then you look at data with cisplatin plus gemcitabine, you will see that the overall response rate. So the tumor’s shrinking significantly. Response is loosely defined as a 30% decline in the maximum dimensions of these tumors, this is seen in an approximately 45, 50% of patients with cisplatin-based chemotherapy. With carboplatin gemcitabine it tends to be around the 40% range so not bad but where the big difference was is in complete remissions, so that is the disappearance of all tumor on the imaging on the scans. That happens with cisplatin-based chemotherapy in approximately 15% of patients, one five, in different cities, 10 to 20% range I would say. But with carboplatin-based chemotherapy you rarely see complete remissions, occasionally you do but rarely, I would say it’s clearly under 5%.

Dr. Guru Sonpavde:

So this is where the big difference is and also when you look at the median survival of patients who got gemcitabine carboplatin… And I can use different studies comparing them head-to-head is a little bit fraught with risks but the median survival of gemcitabine carboplatin treated patients was around eight to nine months. While with cisplatin plus gemcitabine or the MVAC, the median survival is in the 14 to 15 month range. So, again, this is comparison studies and these are different populations but those are the data.

Rick Bangs:

So it’s kind of a directional read?

Dr. Guru Sonpavde:

Yes.

Rick Bangs:

You kind of hinted at this but I want to come back to who gets platinum chemotherapy because we know chemotherapy’s going to be the standard option but we do have groups of patients who can’t get platinum chemo. So let’s talk about bladder cancer. Bladder cancer is not one thing, as we know, and so there’s different types of bladder cancers. And are there people who would respond to platinum chemotherapy based on the type of bladder cancer they have or is it kind of a universal thing that platinum works across?

Dr. Guru Sonpavde:

Good question. The standard of care, just to go with metastatic disease first, the patients who are eligible for cisplatin are those that have urothelial carcinoma. So they have to have the most common type of urinary tract cancer which is urothelial cell type. Most of the trials have included patients with pure urothelial or predominant urothelial carcinoma, meaning some of these patients can have a component of another cell type like squamous or adeno or something else, sometimes heart cormitard micropapillary. There are other cell types that can be found so as long as the majority component with urothelial or it was pure urothelial, these patients are the ones that have been included in clinical trials. So we extrapolate from that to other patients who may have, maybe a minor urothelial component and a major non-urothelial component like squamous or adeno where the data is less certain because we just have not included those patients. Now the vast majority of patients will be pure urothelial or predominant urothelial. So really when we talk about these various cell types, you’re talking about, fortunately the minority of patient in the 20, 25% range.

Dr. Guru Sonpavde:

In predominant urothelial carcinoma, patients who are cisplatin eligible because they have good performance status. They’re fit or fit enough, they don’t have to be perfectly fit. Good kidney function which is estimated with a blood test where we measure creatinine and something called creatinine clearance where we like it to be over 60, some people we’ll consider even over 50 creatinine clearance to be adequate for cisplatin. And then, none of these other illnesses like no significant neuropathy, no significant heart failure, no significant hearing loss. So these patients would qualify for first line cisplatin-based chemotherapy. If they’re not eligible for cisplatin, then we would go with the carboplatin-based chemotherapy and here I’m talking about metastatic disease, so far.

Dr. Guru Sonpavde:

Now the other situation we think about cisplatin is the neoadjuvant or preoperative chemotherapy from muscle invasive bladder cancer and muscle invasive upper tract, urinary tract cancer for example, would also be in this bracket. So in this situation we really, really want to go with cisplatin because that’s the only regimen with which we have data for improving survival. A couple of big studies have been done where patients were randomized to going to radical cystectomy upfront or three months of MVAC chemotherapy in the very important swab trial, followed by radical cystectomy. And basically the neoadjuvant of preoperative cisplatin-based chemotherapy improves survival, the five year survival went up by about 14% from 43% to around 57%. And so this really changed the standard of care. While we don’t have similar data for somebody who’s not eligible for cisplatin, so with carboplatin-based chemotherapy we don’t have data to show benefit with neoadjuvant carboplatin-based chemotherapy. So these are the two situations where we use platinum-based chemotherapy first line metastatic disease and in the neoadjuvant.

Dr. Guru Sonpavde:

Now I’ll say a word about adjuvants… And some patients might go to upfront radical cystectomy or upfront nephroureterectomy, the kidney, the ureters come out for an upper tract cancer and they still have not received preoperative chemotherapy. So in patients like that we would give adjuvant or postoperative cisplatin-based chemotherapy. There is not great data for adjuvant chemotherapy in terms of a phase three trial in bladder cancer but in upper tract urothelial cancer there actually is, with a trial called the POUT trial that came out recently last year. There was an improvement in disease free survival, I should say, with adjuvant platinum gemcitabine so most of the patients had received cisplatin gemcitabine. There was a smaller group of patients that had received carboplatin gemcitabine and overall the trial was positive, it was stopped early because the disease-free survival improved with platinum gemcitabine. That was the primary endpoint but when they looked at the subgroups of patients, it looked like the patients who got carboplatin gemcitabine after surgery had a somewhat lower benefit than the ones who got cisplatin gemcitabine.

Dr. Guru Sonpavde:

So, again, the message is that we really want to stick with cisplatin-based therapy in the neoadjuvant or adjuvant situation and also in the first line metastatic disease situation as much as possible.

Rick Bangs:

Okay, so that makes sense. Then as I get older it’s normal for some of these things that you mentioned to get worse, so my kidney function is going to get worse as I get older and our bladder cancer population average age is 72-ish. So the older I get, the more likely I am to have poor kidney function, right?

Dr. Guru Sonpavde:

You are exactly right, there is a age relative decline in kidney function.

Rick Bangs:

And same with my hearing?

Dr. Guru Sonpavde:

Yes.

Rick Bangs:

So lot of these factors kind of come together, because I am aging I’m more prone to getting cancer because older people tend to get more cancers. And bladder cancer patients tend to be on the older side of the cancer spectrum, so these are kind of competing against my ability to get a platinum-based chemotherapy, right?

Dr. Guru Sonpavde:

You are right and one of the things I did not mention when I mentioned patients who they are in eligible criteria for cisplatin, I did not mention old age as a criterion. Now, thing is, turns out that if patients have good kidney function, good performance status and none of those comorbidities like neuropathy, heart failure or hearing loss, we don’t deny such patients cisplatin just because of age if they’re otherwise fit for cisplatin. But, I agree that with age having one of these comorbidities is just much more likely to happen and so I do pay attention to age and look at this. I will also say that, having said that, some of us do still feel uncomfortable giving standard full dose cisplatin-based chemotherapy to somebody who’s 85 or 90 years old.

Dr. Guru Sonpavde:

So I think that there is probably such a thing as age by itself being a problem to tolerate full doses of cisplatin-based chemotherapy or any chemotherapy. I think it needs further study. We do know that there is a geriatric nomogram that was presented many years ago and in fact in that geriatric age group of patients, they looked at factors that cause toxicities of chemotherapy. And actually, GU cancer like bladder or prostate cancer, was actually a risk factor. So GU cancers might be somewhat prone to toxicities simply because of age, that is something to keep in mind. So I do pay age some attention, it is not something to be totally ignored but right now the standard criteria actually defines cisplatin eligibility based on comorbidities, kidney function and performance status and not just age by itself.

Rick Bangs:

I hear many of your friends and colleagues talking about something that I think relates to what you just said, they talk about chronological age. So that’s the birthday that I just had or I’m going to be having versus, I think the term is, biological age which is, “What’s my kidney function? What’s my hearing?” And I might be better than my chronological age would continue. Is that the kind of distinction we’re making here?

Dr. Guru Sonpavde:

I think that is good point. Yes, you’re exactly right but however you can also have a patient who is chronologically high age, let’s say 85. It looks good in terms of performance status, he’s doing everything, good kidney function, none of those comorbidities, yet can be frail. So there is such a thing called frailty in the presence of reasonable performance status, that is actually a different parameter that also needs to be looked at. The level of social support the patient has, cognition. If you recall cognition was not a reason we deemed somebody cisplatin ineligible but all of these things could have an impact and do factor into this geriatric scores, geriatric models. So I think that these are separate parameters that should all be examined, like you said.

Rick Bangs:

Okay, so it’s not kind of, “One size fits all.” Which is why you need to work with the doctor and have the doctor help you make some determinations as to what can work and what can’t work in your particular situation.

Dr. Guru Sonpavde:

Right.

Rick Bangs:

Okay, so now I’ve come to you and you’ve just told me that I can’t have chemo for any one of these reasons that we still talked about, can I still have surgery? If I needed surgery would I still be able to have surgery even though I can’t have the chemo? And are there some of these things that make me ineligible for chemo making me ineligible for surgery also?

Dr. Guru Sonpavde:

That’s a good question. So the answer is, there is clearly an overlap of patients who are no eligible for chemo or let’s say, not eligible for just cisplatin, who may be eligible for cystectomy or may not be eligible for cystectomy. I have seen instances of both happening where patients are eligible for chemo but not cystectomy and the other way around. Now there are reasons why that can happen. So we went over the reasons why somebody might not be eligible for cisplatin-based chemo. The reasons for not being eligible for cystectomy are more of a certain domain, but for example a patient might be frail, very old and despite having good performance status and good renal function, the frailty and the advanced age could render somebody ineligible for radical cystectomy.

Dr. Guru Sonpavde:

I have seen in my experience surgeons and also neurologists who do radical cystectomy, do pay attention to age. And age by itself can sometimes be a factor that renders any major surgery like radical cystectomy fraught with risks. So I think that the factors are different for a surgeon as opposed to a medical oncologist doing chemotherapy. And also, somebody might be very fit but have had a recent significant medical event. For example if you had an MI, a heart attack three months ago within six months, that’s a problem.

Rick Bangs:

Right.

Dr. Guru Sonpavde:

To go through radical cystectomy within six months of a major cardiovascular event can be a problem. So all of these things can make someone eligible for one but not the other sometimes.

Rick Bangs:

In that example you gave, that would be tricky from a chemotherapy point of view too, right? If I have cardio issues-

Dr. Guru Sonpavde:

You are right, it can be problematic for chemotherapy. However, having a myocardial infarction a few months ago is not an absolute contraindication for chemotherapy, I would say. As opposed to radical cystectomy where the surgeons are usually more nervous taking a patient to radical cystectomy within six months of a myocardial infarction.

Rick Bangs:

Okay. All right, so now a different scenario. I can’t have chemo, can I have immunotherapy? I hear a lot about immunotherapy, we know that some good things are happening with immunotherapy for some patients. So if I can’t have chemo, can I have immunotherapy?

Dr. Guru Sonpavde:

Yes, you can in certain situations. Let’s talk about metastatic disease first. So metastatic bladder cancer patient comes in, he’s not eligible for chemotherapy, let’s say not eligible for cisplatin, potentially eligible for carboplatin or there could be category of patients where you think is not even eligible for carboplatin. So basically, ineligible for all platinums, all chemotherapy. So in somebody who is not eligible for cisplatin you can always do carboplatin gemcitabine chemotherapy, followed by maintenance immunotherapy which is the current standard of care for most patients with metastatic disease now is followed by switching immediately to maintenance immunotherapy, the drug called avelumab.

Dr. Guru Sonpavde:

Now in patients who are not eligible for cisplatin, you have another option which is starting with immunotherapy instead of platinum chemotherapy. So there we have two drugs available right now, one is pembrolizumab it’s an immune checkpoint in the immunotherapy drug given intravenously and this drug is approved for patients who are not eligible for chemotherapy as first line therapy in the first line setting. It’s also approved for following the chemotherapy for progressive disease. But the other drug you can give in the first line metastatic disease setting is atezolizumab. Atezolizumab currently has a slightly broader indication in the first line so it’s approved for patients who are not eligible for any chemotherapy and is also approved in patients who are not eligible for cisplatin and have a PDL1 high expressing tumor. So little bit broader indication at the moment for the first line setting for atezolizumab and that’s just based from the data we have so far. So those are the options we have in the first line setting.

Rick Bangs:

Okay, so I could have some options? All right. Let’s talk about something that I think a lot of patients wonder about which is, why can’t we compensate for some of these obstacles? So the nausea issues with chemotherapy are better today because we have better anti-nausea drugs. Couple examples, so if I have poor kidney function, why couldn’t we use something like dialysis to compensate and push me into an eligible category?

Dr. Guru Sonpavde:

That’s a good question Rick and dialysis is a major procedure really. And in somebody who has kidney function poor enough to need dialysis we have actually done chemotherapy. You have to play around with the timing of the dialysis because these drugs can be dialyzeable you want them to hang around in the blood long enough but not too long. So it is actually a tricky timing with dialysis so that is really an impractical solution to someone having poor kidney function receiving full doses of chemotherapy. So, no that’s not something we’d consider actually in somebody with kidney failure poor enough to need dialysis, but somebody who’s on dialysis, has received chemotherapy we have to play around the dialysis.

Dr. Guru Sonpavde:

So if the dialysis is happening three days a week, we tend to use the day in between the two dialysis sessions so that we have the chemotherapy hanging around long enough for activity but not too long, and can be dialyzed the following day.

Rick Bangs:

Okay, all right. And then hearing loss, so those of us who have some hearing loss… I’m deaf in one ear, can we get platinum chemotherapy with the understanding, because you would tell us, that hearing loss is likely going to get worse?

Dr. Guru Sonpavde:

It’s a good point. I have made a distinction between whether you’re doing chemotherapy in a curative setting or a non-curative setting, for example patients who have metastatic cancer where it’s unlikely you can kill this patient in most cases. Some patients with only lymph node spread can be cured with cisplatin-based chemotherapy but if any other visceral sites of metastasis are present like liver or lung, these are not curable patients. So it makes sense to give it gentler version of chemotherapy that is not too toxic in a patient like that, that you cannot cure with chemotherapy so I might want to use carboplatin gemcitabine and not cisplatin. If you have sever hearing loss just so I can maintain your quality of life with the gentler version of chemotherapy.

Dr. Guru Sonpavde:

On the other hand. If you have muscle invasive bladder cancer without metastasis, you’re potentially curable and if I deliver a neoadjuvant or preoperative cisplatin-based chemotherapy and improving your cure rate, that is a situation where you might accept some decline in your hearing in return for an improved cure rate. So these are discussions we get into base on the setting of the patient if the risks and benefit balance make sense to do the cisplatin or whether we should replace the cisplatin with a gentler platinum like carboplatin.

Rick Bangs:

So you’re going to have a conversation with me about this, if it applies, and we’re going to come to some sort of shared decision what the right plan is for me?

Dr. Guru Sonpavde:

That’s right. And in some cases where we do decide to go with cisplatin, maybe we can keep a closer eye on the hearing. We get a ENT doctor in while we measure hearing. That kind of early monitoring is something we have instituted in some cases.

Rick Bangs:

All right. I think we’ve touched on this but I want to just kind of make it crystal clear. So if I’m not eligible for platinum chemotherapy, what are my options? I think I hear immunotherapy might be an option, there might be… I’ve heard people talk about maybe TURBT, kind of a surgical option but not as comprehensive as a cystectomy. So what are the real options for me if I’m not eligible for platinum chemotherapy?

Dr. Guru Sonpavde:

Right. So, again, in the metastatic disease setting we can, of course, chart it ateizolizumab or pembrolizumab in the appropriate setting. One promising regimen that might be available soon, we’re waiting for more data, is a combination of immunotherapy pembrolizumab with a drug called enfortumab vedotin. This is an antibody-drug conjugate that is approved following prior-therapy but a trial is looking at it the first line treatment in patients who are not eligible for cisplatin. So that will be available, we’ll have to wait and look for more data.

Dr. Guru Sonpavde:

Now in the neoadjuvant and adjuvant settings, so these are patients with muscle invasive bladder cancer… Let’s say they’re up to go for cystectomy, if they’re not eligible for cisplatin in the preoperative phase… We don’t have any other agent approved at the moment, we have clinical trials looking at immunotherapy like immune checkpoint inhibitors but nothing approved. So these patients go straight up to a radical cystectomy, after radical cystectomy if someone is not eligible for cisplatin we actually have a immunotherapy drug approved for adjuvant postoperative therapy. This is a drug called nivolumab it’s a PD-1 inhibitor so this has been approved in patients who are at high risk for recurrence and have had the surgery like radical cystectomy or nephroureterectomy. In patients who are not eligible for cisplatin or who have had neoadjuvant cisplatin and still have high risk muscle invasive disease at the time of cystectomy or nephroureterectomy, I have offered adjuvant nivolumab which is a year of treatment given intravenously.

Rick Bangs:

Okay and is there anything else in the pipeline in the clinical trial space?

Dr. Guru Sonpavde:

There are many drugs emerging in the clinical trial space. I would also mention that there is targeted drug called erdafitinib, which is approved in metastatic cancer progressing after platinum. So this only possible in about 15% to 20% of patients who have an FGFR3 or FGFR2 gene mutation in the tumor cell. That is only after chemotherapy where it’s approved at the moment but it is being looked at in the first line setting in a trail ongoing in patients who are not eligible for cisplatin and have this FGFR3 activating mutation or sometimes it’s a fusion. This drug has been combined with a PD-1 inhibitor serilumab and the data were out at ESMO conference recently which showed some promise for the combination of erdafitinib, the FGFR inhibitor with the PD-1 inhibitor in the first line setting cisplatin ineligible metastatic patients who had this FGFR3 or 2 activating mutation or fusion.

Dr. Guru Sonpavde:

So that’s one and of course the other one enfortumab vedotin plus pembrolizumab combination, which looks promising in this first line cisplatin ineligible setting. There are other combinations being looked at, which one is ipilimumab plus nivolumab, this is a combined immune checkpoint enabler combination that has looked promising after chemotherapy. So there is a phase 3 trial going on that is comparing this ipilimumab plus nivolumab combination and there is no chemo in this combination. It’s a double immunotherapy combination that’s been compared with gemcitabine plus platinum for cisplatin ineligible patients, so basically works as carboplatin inside the brain. And they’re also looking at it in imperial one high expressing tumor patients as a separate group in a phase three study, so hopefully we’ll see some data from the phase three study next year.

Rick Bangs:

It sounds like there’s a fair amount of activity which is good news for us as patients. And so if I’m trying to figure out what’s available to me, one option I would have would be to go to the BCAN clinical trial dashboard or I could reach out to my doctor and my doctor could help me navigate that because it’s pretty tricky to find a clinical trial as a patient.

Dr. Guru Sonpavde:

You’re right Rick. Finding a trial can be challenging and on the trials.gov website that is a good start and the BCAN dashboard I agree is quite well updated for the bladder cancer patient. I think that this is a good start but the situation is that the status of a trial can change week-to-week and even day-to-day sometimes, so it is something that patients would seek, hopefully with the guidance of the physicians at the institutions they’re at, to help them navigate the quite complex landscape of clinical trials.

Rick Bangs:

Okay. All right. So Dr. Sonpavde thank you so much for your time today and giving us a better understanding why chemotherapy is not an option for some bladder cancer patients and what they can do instead. I know you’ve given our listeners important information and options to consider so thank you.

Dr. Guru Sonpavde:

Thank you, Rick.

Rick Bangs:

In case people would like to get in touch with you, would you like to share a Twitter handle or any other information that you’d like people to have?

Dr. Guru Sonpavde:

Yes, my Twitter handle is @Sonpavde S-O-N-P-A-V-D-E. They can also email me at Dana-Farber email gurup_sonpavde@dfci.harvard.edu

Rick Bangs:

Okay, thank you. Just a reminder, if you’d like more information about bladder cancer you can contact the Bladder Cancer Advocacy Network at 1-888-901-2226. That’s all the time we have today, thank you for listening and we’ll be back soon with another interesting episode of Bladder Cancer Matters. Thanks again Dr. Sonpavde.

Dr. Guru Sonpavde:

Thank you very much Rick.

Voice over:

Thank you for listening to Bladder Cancer Matters, a podcast by the Bladder Cancer Advocacy Network or BCAN. BCAN works to increase public awareness about bladder cancer, advanced bladder cancer research and provide educational and support services for bladder cancer patients. For more information about this podcast and additional information about bladder cancer, please visit bcan.org