Transcript of Bladder Cancer and Chemotherapy Drug Shortages

July 6, 2023

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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 B-C-A-N dot O-R-G.

Rick Bangs:

Hi. I’m Rick Bangs, the host of Bladder Cancer Matters, a podcast for, by, and about the bladder cancer community. I am also a survivor of muscle-invasive bladder cancer, the proud owner of a 2006 model 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 the Seagen Astellas Alliance.

I am pleased to welcome today’s guest, Dr. Gopa Iyer. Dr. Iyer is a medical oncologist at Memorial Sloan Kettering Cancer Center, where he is section head for urothelial cancer. He focuses on the care of patients with bladder cancer. His research interests include development of novel therapies for patients with advanced bladder cancer and defining biomarkers that predict response to these therapies. He also leads a clinical trial exploring whether some patients with muscle-invasive bladder cancer can be treated with chemotherapy alone with the need for surgery. Dr. Iyer, thank you for joining our podcast.

Dr. Gopa Iyer:

Thank you so much for having me on, Rick. I’m really excited to be on Bladder Cancer Matters and to have this very timely discussion with you today. Especially happy that your 2006 model is going strong still.

Rick Bangs:

Thank you. Thank you. We’re thrilled to have you here as well.

All right, so this spring, we had more shortages in cancer of drugs, and so there were a number of cancer drugs that became in short supply, and that includes a number that are used to treat bladder cancer. Can you tell us what drugs are in short supply?

Dr. Gopa Iyer:

Sure, yeah. The current drug shortages that have been specifically reported by the FDA and are really impacting our patients are … Of course, the two big ones are carboplatin and cisplatin, which we do use quite a bit in the management of bladder cancer, but there’s also others, including fluorouracil, which is used in a lot of different cancer types, including colorectal cancer and some bladder cancers. Capecitabine, which is an oral form of fluorouracil, and then docetaxel as well are all in shortage this year.

Rick Bangs:

Wow. Wow. All right, so those drugs are used in what types of cancer?

Dr. Gopa Iyer:

Yeah. The platinum agents, as you and I think our audience knows well, those are used in a lot of genitourinary malignancies, of course, bladder cancer being one of the big ones. Testes cancer as well, platinum therapy, especially cisplatin, is still a cornerstone of treatment and really of curative intent treatment for patients with germ cell cancers like testicular cancer. Then there’s a lot of gynecologic malignancies too that utilize cisplatin or carboplatin. We think about ovarian cancer, endometrial and cervical cancers. Then we also think about head and neck cancers. A lot of times, patients receive radiation for those, but they also receive platinum chemotherapy at the same time. Then there are also lung and breast cancers too, where platinum-based regimens are utilized fairly frequently.

Rick Bangs:

Wow, so that’s a large part of the cancer population.

Dr. Gopa Iyer:

It is, unfortunately.

Rick Bangs:

Yeah. So how do we get here? That seems to be the common question. We’ve had this question about the BCG shortage. So how do we get here? What’s the cause of this problem?

Dr. Gopa Iyer:

FDA has done a lot of research into trying to figure out what the cause is, in an attempt, of course, to try to stem this tide of drug shortages in the future. It seems to be multiple factors. One of the big ones is manufacturing delays. Sometimes there can be a shortage of the actual raw materials that are necessary to make these agents. Cisplatin does require platinum, which is a metal.

Then there’s also problems with quality control sometimes within these manufacturing plants. These are drugs that are typically given intravenously, and so they really need to be sterile injections that have to be administered to patients. You can imagine there’s a lot of quality control that has to go into making these agents and making sure they don’t get contaminated in any way. If that breaks down at all, then that can actually shut down manufacturing at a given plant. That’s a big issue.

Then the other big one, of course, is increased demand as well. Just to give you a quick example of that, there was a quality control issue at one of the plants, not within the United States, that makes a lot of cisplatin. They underwent an FDA inspection near the end of last year where they said, “Listen, there’s a lot of QC issues here.” The plant had to shut down production for a while until those issues could be worked out. That actually impacted cisplatin production, but it actually also impacted carboplatin use as well, because a lot of times or in certain situations, you can use carboplatin instead of cisplatin. As you can imagine, the demand for carboplatin went up and the supply for carboplatin couldn’t meet that demand. That’s why we have both cisplatin and carboplatin shortages right now.

Rick Bangs:

Wow, wow. I certainly don’t want them to take any shortcuts on quality control. That’s kind of important.

What are the long term and the short-term solutions to these particular shortages?

Dr. Gopa Iyer:

Yeah, so some long term solutions, and this is one of the ones that’s going to sound kind of obvious, but actually is a big issue, is for manufacturers and the FDA to basically have clearer lines of communication between each other. The FDA has been asking for drug manufacturers to really notify them as soon as possible if they start to see any issues that might impact their drug shortage, because that’s the only way that they can then have an early warning system to try to mitigate the effects of the shortages that are coming up as much as they can.

Something else that’s been brought up by FDA, I think, as well as by Congress and has been thought about, is actually developing stockpiles of some of these drugs to try to prevent the effects of acute shortages that might come up in the future as well. So very similar to trying to develop stockpiles of vaccines for the COVID pandemic and other viral infections and trying to do that or apply that same issue to these drugs as well.

Then a third is really just to try to invest in better technology to be able to improve production of these drugs and to try to invest in what they call quality management as much as possible these types of practices, to try to reduce the likelihood of disruptions to the supply chain. Those are very longterm solutions that they’re looking into.

One of the big issues though is what about the short-term solutions for patients right now when we’re already in the middle of these shortages? For that, there’s a few things. One is, which I think there’s … You can argue for and against this, but setting up a prioritization system. We are at that point right now where we really do need to think about which are the patients or who are the patients who have a cancer that is curable with cisplatin or carboplatin, and should we go ahead and prioritize treatment for those patients first and foremost? That’s being done right now in centers around the country in different ways.

Another is with something that the FDA has done, which is to allow for importation from other countries of these drugs when they may have a supply of the drug. There’s a company in China that has been able to produce more platinum agents, and so the FDA has temporarily allowed for importation of platinum from that source as well.

Rick Bangs:

Yeah, because in this case, some other countries are not experiencing the same problems because different manufacturers are providing them with drug, right?

Dr. Gopa Iyer:

That’s exactly right. That’s exactly right. Whereas we tend to be reliant on a small number of manufacturers, and so if one of them stops production, that really impacts us significantly.

Rick Bangs:

Right. Or if the raw material that all of the suppliers use is in short supply, then nobody can produce it, even though you’ve got multiple people ready to produce.

Dr. Gopa Iyer:

Exactly. Exactly.

Rick Bangs:

Okay. When did these shortages begin, and how long can we anticipate them continuing?

Dr. Gopa Iyer:

Yeah, so for cisplatin, the FDA reported shortages, I think, in February. For carboplatin that the shortage was reported a little bit later, around the end of April or so. They’ve known about this now for a few months. Your question is, of course, the big one, which is how long is this going to keep going for? Unfortunately, it’s really not clear when they’re going to be resolved. It truly is a moving target right now that depends on when these manufacturers meet the quality metrics that they need to meet in order to move forward with producing the drug consistently.

I would say, especially to this audience, you may hear potential dates for when the shortage is predicted to end. We really can’t assume that those are going to be accurate, and so we need to always be prepared for a longer shortage or for the shortages to be lasting longer.

Most of the manufacturers are operating near capacity, so they oftentimes aren’t going to be able to step up production even more so. We’re really trying to, as you put it before as you alluded to, is trying to fix the root cause, which is if we can just fix the QC issues that some of these manufacturing sites, or at the major one, then hopefully production will pick up quickly after that.

Rick Bangs:

Yeah. I used to manage back orders in my business career, and I remember how chaotic it was to allocate supply. But then to your point, you’re coming out of a shortage situation and it’s very volatile. There’s chaos now because your data doesn’t reflect what you really need. It reflected what you had available. It’s just messy.

Dr. Gopa Iyer:

That’s right. That’s right. Yeah, we’re always a little bit behind in terms of what we’re seeing. Yeah, yeah.

Rick Bangs:

Okay, so is bladder cancer disproportionately impacted here?

Dr. Gopa Iyer:

Yeah. I would say any cancer type that uses platinum chemotherapy right now is being impacted. There is data on this. The National Comprehensive Cancer Network, or NCCN, they did a survey of about 27 major cancer institutions to get a sense of how they’re being impacted by the platinum shortage. This was released, I believe, in May, so pretty recently. They said that 93% of cancer centers that were polled are experiencing a carboplatin shortage, while about 70% have a cisplatin shortage. Additionally, all of those cancer centers that were polled were able to treat their patients with cisplatin without significant delays or denials to claims from insurance companies, but only about a third were able to keep patients who were receiving carboplatin on their current regimen.

So I think what that really tells us is that even though the cisplatin shortage happened first, it seems that the carboplatin shortage is really what’s affecting patients even more so. That’s really important for us from a bladder cancer standpoint because luckily we do have alternatives to carboplatin now that we didn’t use to have before for bladder cancer. Unfortunately, that’s not the case with other cancer types.

Rick Bangs:

Okay. What kind of alternatives do we have in bladder cancer for carboplatin?

Dr. Gopa Iyer:

When we think about where we use platinum most frequently, we think about it typically for patients who have muscle-invasive bladder cancer, where the plan is that they’re going to undergo removal of their bladder, that they’re going to have a cystectomy. We usually like to give chemotherapy with cisplatin in two different regimens. There’s a couple that are out there, and we like to give that before surgery.

What we found is that the shortage hasn’t really impacted that so much, and so many patients are still able to receive that chemotherapy prior to surgery. If there is a shortage of cisplatin, then the other option we have is for patients to go to surgery upfront, and then we have a non-cisplatin option for them after surgery, which is immunotherapy. There’s an FDA approval for nivolumab and immunotherapy for a year after surgery. That’s a non-chemo option that we have, and luckily we don’t have a shortage of that right now.

Then in patients who have more advanced cancer, bladder cancer, we used to say the only two options really were either a cisplatin-based chemotherapy, or if patients couldn’t handle cisplatin because of different medical issues, then carboplatin. But now, we actually have a different option because the FDA has approved a combination of two different drugs, KEYTRUDA, pembrolizumab, which is our immunotherapy drug, and then enfortumab vedotin, or EV, that combination for patients who wouldn’t be able to tolerate cisplatin-based chemotherapy. Those two drugs are not in shortage right now, so we do have those. It’s a very effective what we call platinum-free combination treatment for patients.

Rick Bangs:

And very recent additions to the portfolio.

Dr. Gopa Iyer:

That’s exactly right, just within the last two to three months. Very timely additions luckily, given what’s happening right now.

Rick Bangs:

Good, good. All right, so within bladder cancer, what particular contexts are being impacted here?

Dr. Gopa Iyer:

The muscle-invasive space, so that early stage space is impacted. But again, the argument there is that if patients are at a site where there truly is a significant shortage of platinum, then either going to surgery and then having immunotherapy afterwards would be one option. Or in select patients, they may not need surgery. They could receive chemoradiation. It will be impacted, but hopefully not as much because we have those alternative treatments.

Then in the more advanced stage two now with these non-platinum agents, I think we’re going to see less of an impact for those patients as well.

Rick Bangs:

I seem to remember with BCG, there were guidelines. I think BCAN was involved in guidelines. AUA and some other groups all were preparing guidelines so that people had common marching orders. Have similar guidelines been prepared here? I seem to recall something about the American Society of Clinical Oncologists, ASCO, having some guidelines. What have we got in this context?

Dr. Gopa Iyer:

Yeah, you’re exactly right, actually. ASCO did establish what they called a Drug Shortages Advisory Group specifically to provide some guidance on what to do in the context of these drug shortages. For the gynecologic malignancies, they actually collaborated with the Society of Gynecologic Oncology, or SGO, to try to develop general guidance for GYN malignancies that are commonly using carboplatin-based chemotherapy.

There actually is a Bladder Cancer Advisory Group that includes thought leaders from different academic institutions around the country who have expertise in managing bladder cancer. They have worked on guidance as well for patients with bladder cancer. It actually just came out now and is available on ASCO’s website for how to manage the care for patients with bladder cancer in the context of this drug shortage. They also in that guidance provide or emphasize the fact that there are, again, non-chemotherapy options like the EV plus pembro option, for example, for patients now, so that we can try to avoid platinum chemo altogether in a subset of our patients.

Rick Bangs:

All right, so we talked about some alternatives that might be leveraged here, but if I’m a patient, what should I do? What do I need to know if I’m specifically impacted?

Dr. Gopa Iyer:

Yeah, so I think really talk with your provider. This is really an individualized decision, and providers, i. e., physicians, have to tailor the management based on the situation and based on the patient who’s sitting in front of them, basically. What I would say is, talk to your provider, because your provider will definitely have already received alerts about shortages of specific drugs a while back, and so they’ve probably been aware of it before you have been. Usually, provider networks will have some sort of strategy in place to figure out how to alleviate the impact of the shortage on our patients.

One example that I can give you from just a real-world experience, I did have a patient who needed to get carboplatin-based chemotherapy, and they really didn’t want to commute into Manhattan to receive it with me, and so they were searching for a local physician. They did find a local oncologist, but ultimately that oncologist had a shortage of carboplatin. They said, “We could try to get it for you, or there’s actually three other sites that we work with closely that do have carboplatin that are within our network.” So a lot of times, even though your individual care provider site may not have access to it, they can usually identify others within the area that do have some supplies. There is a network. There’s a sort of cooperation amongst physicians as well to try to make sure that patients have the best outcomes and have access to these drugs.

Rick Bangs:

Yeah, that’s great to hear. All right, any more work happening in this space?

Dr. Gopa Iyer:

Yeah, to try to prevent this from happening altogether, right? That would be ideal.

FDA, they have been doing a lot of work on this. What’s interesting is that the drug shortages, even though we’re hearing about them a lot right now and primarily because they are these really critical cornerstone drugs like platinum agents, but these new drug shortages were happening even back a decade ago. 2011 actually had the most with about 250 new drug shortages.

Rick Bangs:

Wow.

Dr. Gopa Iyer:

I know. It’s a lot. Because of a lot of the efforts by the FDA, that number’s come down to around 50 per year. It’s still not acceptable. Obviously, we want to do better, but it is a lot better than it was back then. The problem, of course, is the shortages are still posing a big challenge to public health, and so we have to continue to find ways to prevent them from happening.

The one thing I will say, we don’t hear about this a lot, but actually by working with manufacturers, the FDA was able to avoid about 222 shortages last year that would’ve otherwise happened. A lot of that was because of communication that was happening early and often between manufacturers and the FDA to find ways to diversify their supply chain, et cetera, to prevent those shortages.

Rick Bangs:

Yeah, and we know the FDA is working hard to figure out how to do a better job in this space.

Dr. Gopa Iyer:

Yeah.

Rick Bangs:

Okay. Any final thoughts?

Dr. Gopa Iyer:

To be honest with you, the other thing I would say is that we as physicians and researchers in the bladder cancer space just need to keep working hard at trying to develop novel drugs because we’re talking about platinum chemotherapy, which has now been around for 30 to 40 years and still is a cornerstone of how we manage patients with bladder cancer. But we need to identify better approaches that are non-platinum-based approaches and try to really reduce our reliability on the platinum agents, so that if there are going to be shortages, that we have even better options for our patients.

Probably the other thing is, if we can better identify, whether it’s through a genetic marker or some other method, who upfront is going to be somebody who would benefit most likely from platinum and who is not going to get any benefit from platinum, then that really lets us prioritize our treatment for the patients who are most likely to benefit. So more coming on that end is what I would say.

Rick Bangs:

Yeah, yeah. That’s such an important point here because even with BCG, if we knew who needed to get it, if we knew who needs to get chemotherapy and they get it, and people who don’t benefit from it don’t, that’s a win-win.

Dr. Gopa Iyer:

Yeah, yeah. It’s not a one size fits all.

Rick Bangs:

Yeah, exactly.

Dr. Gopa Iyer:

[inaudible 00:20:21].

Rick Bangs:

Exactly. All right. So Dr. Iyer, I want to thank you for this really important update on the drug shortages that are impacting the bladder cancer community and for giving us some direction on what is being done and how patients should handle the situation.

Dr. Gopa Iyer:

My pleasure. Thank you again for having me.

Rick Bangs:

All right. If you’d like more information on bladder cancer, please visit the BCAN website, www. B-C-A-N .org.

For more information on shortages of drugs in bladder cancer, visit the BCAN website and enter shortage in the search box.

Just a reminder, that if you would 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. If you liked this podcast, never miss an episode by clicking on the subscribe button on your favorite podcasting platform. Rating our podcast also helps us reach more people. Please feel free to leave a review as well.

Thank you for listening, and we’ll be back soon with another interesting episode of Bladder Cancer Matters. Thanks again, Dr. Iyer.

Announcer:

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 B-C-A-N dot O-R-G.