"There are going to be more trials open for those patients who may not have received BCG...I think that's essential, to realize that there are other treatments on the horizon for patients with non–muscle-invasive bladder cancer," says Sam S. Chang, MD.
The BCG shortage has been a prominent issue in the world urology for many years, making it more difficult for patients to receive the care they need for non-muscle invasive bladder cancer.
To give updates on the state of the BCG shortage, Urology Times® Assistant Editor Janelle Hart spoke with Sam S. Chang, MD, MBA. He emphasizes small improvements in the shortage over recent years, but simultaneously stresses the need for a solution. He also mentions what initiatives are taking place currently to help resolve the issue. Chang is a Patricia and Rodes Hart professor of urology and oncology at the Vanderbilt University Medical Center and chief surgical officer at the Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee.
When we talk about BCG shortage, some places haven't experienced any shortages at all. Some of the same cities, some institutions within miles of other institutions, have experienced shortages and others have not. And so, I would tell you that it is definitely improved from probably the last year or so, but there are still cities, institutions, locations, that do not have BCG. Why that is it depends upon distribution of the medication, and how that distribution actually takes place is a very complex web that I don't think anybody has ever figured out. I will tell you that there are still sporadic shortages of BCG in the US.
In the US, the only approved current version of BCG is called TICE BCG. It's a subtype of BCG and it's only made by 1 manufacturer, and that manufacturer is Merck. Merck announced probably about a year ago to this day that they are building, in the Research Triangle in North Carolina, a brand-new manufacturing plant that is built specifically to make more BCG with the goal to actually triple what's currently being produced in the US. So, that was met with a lot of enthusiasm but there are caveats to that. And to Merck’s credit, they tried to calm people down in terms of the fact that it's going to take some time to ramp up, that you have to build the building, which will take years—5, 6, 7 years is what they estimated—and that the ramp-up will be gradual over time. To be honest with you, I don't know if they've actually even broken ground yet on that facility, but that's the main thing, that there is going to be more BCG made by Merck.
Now, importantly, there are also clinical trials in the US. There's a clinical trial out of SWOG led by Rob Svatek [MD],1 who is examining the priming of an individual with a subcutaneous injection, but also looking at a different form of BCG, a BCG sub strain called Tokyo, and seeing if that's actually effective. And so, we are looking at the studies, different types of BCG strains. We are going to increase production of BCG and there's some thought that certain generic companies are coming into play that hopefully would also be able to produce BCG, but making BCG is not so easy. Its quality concerns are essential and paramount because we're actually giving this medication to patients that have a formulation that can cause illness and we have to worry about the quality of the formulations. There are a lot of things going on that take place that make it difficult to make BCG, but hopefully in the future we will not have a BCG shortage.
To be honest, over the past year, we have not. Prior to that, we definitely had BCG shortages. And so, we went through a process and with the aid of what the American Urological Association has outlined in terms of the correct patient population and how we prioritize. We spoke with all patients who were getting BCG and we made it quite clear that there was a national BCG shortage, that we had a limited supply of BCG and there were times we had no BCG, and that we were prioritizing those patients that had high-risk disease that had not yet received BCG. So, induction patients were the ones that we saved our BCG for. We also did, for a limited period of time, reduce the amount of BCG. We actually shared vials. At that point, it was a communication with each of the patients and minimize those that were lower risk or who are on maintenance therapy and emphasize those that were of higher risk and were getting induction therapy.
Over time, as we understand who should be getting BCG and really try to emphasize that, as we understand other options that are available for patients that may not necessarily need BCG, we’ll gradually, as an entire country, have less issues with shortages. But I wouldn't be surprised if we have spotty distribution areas of concern for the next several years. And so, it's something that I think we all need to be ready for and ready to make sure our patients understand that too because many come from different areas where they don't have BCG. And they've been told that they may not be able to get BCG locally for years and years, if ever.
This is an exciting opportunity for all our patients that may need intravesical therapy or may need other therapies for higher risk non–muscle-invasive bladder cancer. There's been an explosion of clinical trials, where there are probably more trials than are patients available for those patients who have not responded to BCG. That's very exciting. As these trials start accruing, there are going to be more trials open for those patients who may not have received BCG. I think that's essential, to realize that there are other treatments on the horizon for patients with non–muscle-invasive bladder cancer.
The second thing is that clinicians should continue to understand the importance of risk stratification. We are overtreating some patients and we are undertreating some patients, so the more information we get on how risky a patient's cancer is, I think the better we'll be able to adapt therapies. I think clinicians as a whole have improved their ability and they've been more cognizant and aware of how important that that risk stratification is.
1. Svatek RS, Tangen C, Delacroix S, et al. Background and Update for S1602 "A Phase III Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming with Intradermal BCG Before Intravesical Therapy for BCG-naïve High-grade Non-muscle-invasive Bladder Cancer. Published online September 6, 2018. Eur Urol Focus. doi:10.1016/j.euf.2018.08.015