Alicia Morgans: Hi. I'm delighted to have here with me today a wonderful urologist and friend, Dr. Josh Meeks, who is an Assistant Professor of Urology at Northwestern Medicine. Wonderful to have you here.

Joshua Meeks: Thanks, Alicia. It's always a pleasure.

Alicia Morgans: Wonderful. Josh, we have already talked multiple times about the BCG shortage, the implications, how we understand the problem and how we put together plans to move forward in a meaningful way. Recently at GU ASCO, we saw data from a European trial that really raised concerns from my perspective about how we might be managing some of these high-risk BCG-naïve patients if we don't really have a set strategy to think rationally about how we use our BCG. For example, if we just missed doses or change our dosing schedule, it seems like there could be implications. Can you tell us a little bit about the NIMBUS trial?

Joshua Meeks: Yeah, I mean, I think the really nice example of this was today, this morning at GU ASCO, there was a great panel discussion about non-muscle-invasive bladder cancer and how we manage it in 2020. Sam Chang really nicely talked about the problem of what do we do in an era with limited BCG resources. One thing that we talked about was limiting the doses, about trying to make sure we get through at least the first induction. Ideally for high-risk patients, if you have BCG, we should treat them for a year.

This NIMBUS study, a very interesting study out of Europe, 400 patients that were included in the intention to treat analysis. What's really interesting is that it's not like it's a huge difference, I'll say. The standard regimen was doses one through six, and then they got maintenance dosing three of them at three, six and 12. That's a relatively standard regimen.

The comparative regimen was dosed at one, two and six weeks, so half the number of doses, and then doses at one and three weeks at the same regimen, three, six and 12. You're not really missing that many doses in this trial. What they showed was a hazard ratio of 0.4 for people who were in the reduced doses.

I guess what I worry about that interpret that in the US is there's a lot of people who miss doses. Some of that is understanding, some of that is education from the urologist's perspective. I mean, I would tell you before the 2016 guidelines, maintenance really wasn't appreciated and maybe that's the reason we have a shortage quite honestly, is that a lot of people read the guidelines. I said, wow, I should be giving BCG. We start applying that guideline to patients. We're giving a lot more BCG. We end up with a shortage and now we're having to ration a little bit. I guess just looking at that data, I'm very interested to see what our data will look like over the next few years in the US when we are reducing dosing or potentially giving less BCG, are we going to see that change in outcome for patients?

Alicia Morgans: Absolutely. This was a sizable study.

Joshua Meeks: Yeah, really well done.

Alicia Morgans: Very, very well done. The doses were given at full dose, but there were fewer doses given, which may be a strategy that some are considering at least as they're trying to rationally deal with the BCG shortage. When we compared those patients getting full dose, they actually had a 60% reduction in recurrence as compared to those patients who are getting this reduced dosing frequency.

Joshua Meeks: This was a pretty high-risk population. I think the rate of carcinoma in situ, if I remember right was around 25 to 30%, but there's a lot of T1's. It was a neighborhood of over 50% of patients were T1'a, and that may be why really if you can give them at least the six induction and get them through the minimum of the first year why we think that's important.

Alicia Morgans: Absolutely. How are you thinking about making sure that this doesn't happen in your practice and what would you recommend to folks? Say they say, well I just have half as much BCG around. How do I pick the patient that gets the BCG and to whom do I give something else?

Joshua Meeks: Again, I think that's one of the benefits of our risk stratification process. High-risk patients, so T1's, carcinoma in situ, really prioritizing those patients getting full dose and getting a year of therapy.

The sense I get is that while there is a shortage, people are figuring out who has BCG and who doesn't, or at least who has trial options for patients. Again, one of the reasons we have sufficient BCG at our institution, Northwestern, is that we have a trial open, SWOG 1602, which allows patients to come on that and then that frees up BCG for other patients that can't qualify to be on that trial, but at least everyone's getting BCG. I think the first thing is to try to get them, if you don't have it, try to get them to someone who does.

I think the other thing again we've talked about is if you don't have BCG alternative mechanisms. Again, I worry about those because they've never really been compared head-to-head in a trial experience such as gemcitabine docetaxel. Probably the second-best regimen that we've seen. Mike O'Donnell's publish on the data looks really good, but has never been head-to-head compared to BCG. If you gave me my druthers and I had the choice, I would choose BCG. The third part is to do a good job as a surgeon. I mean again, if it's T1 disease, a lot of that disease can be resected surgically, so making sure you do a primary TUR, you do a re-TUR and then follow patients very closely.

Alicia Morgans: Absolutely. There are some strategies to make sure you have a complete TUR, things like Blue Light and other ways to just really make sure that you're visualizing all that could be there.

Joshua Meeks: Right. Again, what that adds to it is that you're removing all visible disease and honestly all those things that you wouldn't even have seen before. The hope is by doing a better TUR, we're reducing those recurrences.

Alicia Morgans: Absolutely. Well I, as always, appreciate your expertise as we continue to really deal with a BCG shortage. I don't feel like this is going to be something that's short-lived. In fact, we've been told that it is not something that will be short-lived. Always thinking through what are the consequences if we make changes are important, and it's actually very, very helpful to see that a group has done a study that helps us understand those consequences pretty clearly.

Joshua Meeks: Clearly a need, right? I mean again, it highlights the fact that we need to figure out both who are going to benefit the most from BCG, and then the next step is, are there better ways to treat these patients?

Alicia Morgans: Absolutely. Well, thank you so much for your time.

Joshua Meeks: Thanks, Alicia.