ImpediMed Limited (IPD) Earnings Call Transcript & Summary

Thank you for standing by, and welcome to the ImpediMed Investor Update Meta-Analysis Publication. [Operator Instructions]. I would now like to hand the conference over to Mr. Richard Carreon, Managing Director and CEO. Please go ahead.

Thank you, Amanda. Good morning, and thank you for joining us this morning. This call is to discuss the meta-analysis that was published this weekend in Breast Cancer Research and Treatment journal. With me today are Cathy Kingsford, our Senior VP of Clinical and Regulatory; and the lead author of the meta-analysis, Dr. Chirag Shah. Before I turn the call over to Dr. Shah, let me provide you a summary of his impressive background. Dr. Shah is the associate staff in the Department of Radiation Oncology and Director of Clinical Research in the Department of Radiation Oncology, the world-famous Cleveland Clinic. Dr. Shah received his Bachelor's degree from Youngstown State University and his medical degree from Northeast Ohio Medical University. He completed his internship and residency at William Beaumont Hospital from 2007 to 2012 and joined the Cleveland Clinic staff in 2015. Dr. Shah serves as a reviewer for various medical journals and is a member of various medical society. His primary research interests are breast cancer, sarcoma, prostate cancer, lymphoma and innovative radiation treatment schedules as well as lymphedema. He has participated in numerous in-house pharmaceutical and cooperative group trials. He is the co-editor of Radiation Oncology section of American Society of Breast Surgeons BESAP program, a member of the American Brachytherapy Society, Partial Breast Irradiation and Guidelines Committee. Dr. Shah, would you please provide a summary of the meta-analysis as well as the key highlights from the analysis for everybody who's dialed in?

Good morning, everyone, and thank you for the kind introduction, Rick. I'd like to present the meta-analysis, which is entitled the impact of monitoring techniques on progression to chronic breast cancer-related lymphedema: a meta-analysis comparing bioimpedance spectroscopy versus circumferential measurements. And this was just published in Breast Cancer Research and treatment. As an introduction, this meta-analysis was an update of the previously published DiSipio meta-analysis in 2013 in the Lancet. That study identified that roughly 20% of patients would subsequently develop breast cancer-related lymphedema though significant heterogeneity exists based on measurement technique, patient treatment factors, including the use of mastectomy and axillary lymph node dissection as well as follow-up. Therefore, our methods included an update beginning in 2013 when the previous analysis published to 2019 when we begin our analysis. We picked any studies that were able to report breast cancer-related lymphedema rate at any postsurgical time point. In the background group, it is a group of patients that is consistent with the previous DiSipio meta-analysis. So it has included anyone that was not receiving bioimpedance spectroscopy or tape measurements such as techniques for monitoring like water displacement, and we did not exclude any monitoring technique to be consistent with the previous meta-analysis. This research was conducted by multiple authors and reviewed with consensus based on the inclusion and exclusion criteria provided in the method. This also met national and international guidelines for meta-analysis based on the PRISMA guideline. After all analyses were reviewed, we identified 50 studies that met our criteria, and that's displayed in figure 1. Importantly, 9 of these studies were randomized control or level 1 studies, 27 prospective studies and 14 retrospective. Together, these studies allowed for 35 cohorts within the background group, 11 in the tape measure group and 7 in the bioimpedance group with 3 studies contributing to more than one of those groups, hence, the 53 total. Overall, this led to [ 11,000 ] patients being included in this analysis. Patient characteristics are presented in Table 1 by the groups that we evaluated, and we subsequently performed subgroup analysis that to account for some of these differences that you see in table 1. Table 2, the detailed study list, providing the information for each of the groups and the study characteristics. In terms of results, the first result we looked at was the annual incidence of breast cancer-related lymphedema. When looking at the background population, the annualized incidence rate was 4.9% as compared to 7.7% was circumference and 1.5% was bioimpedance. When looking at the cumulative incidence 12.9% was backgrounds, 17% was circumference, and 3.1% was bioimpedance. This represents a 69% reduction with BIS as compared to background and an 81% reduction as compared to circumference. We then performed a series of subgroup analysis, and this is important because we wanted to account for differences between studies, but also look at high-risk groups. So first, we looked at follow-up. And we look at studies that had less than 2-year follow-up and greater than 2-year follow-up. And importantly, in the greater than 2-year follow-up, these findings held. So the difference between this and the tape measurement group was 0.8% versus 6.9%, which is a relative risk of 0.12 and highly statistically significant. The same held was BIS as compared to background measurements. Importantly, when we look at randomized controlled trials alone or level 1 studies, the benefits still held with a 0.5% rate with bioimpedance as compared to 7.1% with tape measurement. And these results are presented in table 3 of the manuscript. Table 4 looks at high-risk clinical features. And we really, in particular, want to focus on these 2 factors seen in the previous DiSipio meta-analysis, meaning axillary lymph nodes dissection and mastectomy. When we look at studies that had an axillary dissection rate of greater than 50%, there was a still 56% reduction with BIS as compared to tape measurement, 6.9% versus 15.4% or a relative reduction of 0.44 highly statistically significant. Similarly, with mastectomy, when we look at a cut point of 40%, a 79% reduction with BIS as compared to tape measurement was seen. In summary, these results show that the improvement seen with BIS are not only statistically significant, but clinically significant, with a nearly 70% reduction as compared to background and an 80% reduction as compared to tape measurement. This clearly shows that tape measurement has limited to no benefit clinically in the detection of early-stage breast cancer-related lymphedema. These findings also held in high-risk population. In terms of limitations of the study, one comment is why the background rates were, for example, lower than the circumference measurement. And this is likely due to the fact that there's high variability in an inter-observer variability with tape measurement. But also when we perform sensitivity analysis with background, we found that the no monitoring studies included actually have lower rates than the monitoring, so it wasn't that the monitoring studies included in the background bias the results. And with that, I'm happy to hand it back to Rick.

Thank you, Dr. Shah. Listen, I want to keep the questions this morning, at least in the beginning, focused on clinical. And then if there's any business questions, we can wrap the call up with that because we do have limited time this morning. So with that, let me open up the lines, Amanda, for questions. And then please keep your initial questions to clinical aspects of the meta-analysis.

[Operator Instructions] Your first question comes from Shane Storey from Wilsons.

Perhaps we can start by just looking at the 35 background studies included, just to take up Dr. Shah's point just in his closing remarks there. Am I right in thinking of those studies, those background studies is observational natural history type studies? And then on the BCRL incidence that you detected in those publications, that overall figure, you sort of called out that sort of 12.9% was a little low. But I mean, how -- I mean, when you say that, what are you comparing it to? And then maybe if you could please comment on how representative that was in terms of sort of the higher and the lower risk patient groups that you typically see presented [ in practice ]? That's one question.

So I'll walk my way through it and hopefully in each part. So in terms of the cumulative incidence of 12.9% with background, it is a little bit lower than the previous DiSipio analysis, but I think that also reflects moving away clinically from high rates of axillary lymph nodes dissection and high rates of mastectomy. So I think that, that meets kind of the modern thinking of what a rate of background would be. So I think that's kind of the one issue. In terms of the other question is, is this background group kind of just overall -- looking at the overall milieu, I think that's fair to say. Obviously, those monitoring studies make it a little bit cloudy, but that's how the DiSipio analysis did it. And so we wanted to make sure it was consistent but interestingly, when we did the sensitivity analysis, the monitoring studies had a slightly higher rate of recurrence than the no monitoring studies. It was about 3.7% annualized with no monitoring versus about 7.6% with monitoring. So I don't think that the monitoring studies biased the background to be lower than expected overall. And then in terms of the population, when you look at the overall population, which is kind of published in figure -- sorry, table 1, we do see the rates of, for example, regional nodal irradiation, chemotherapy and these types of factors. And what you see is that what you're going to see in a very large analysis, which is that there are some small differences. So if you look in the mastectomy rate, it's 35%, 37%. But then the BIS is actually slightly higher. So very biased against the BIS patients, but still that benefit was shown. Similarly, when you look at the dissection rates, they're relatively comparable, 29%, 25% and 28% and then when you look at the chemotherapy, again, the BIS studies were slightly higher. Small difference in terms of regional nodal irradiation. But when you look at it, they're relatively well balanced. And if anything, on the totality of it, slightly biased against the BIS study.

Okay. That's interesting. And look, just turning to the BIS benefit specifically. I mean there's clearly some really strong differences there between BIS and tape, especially in the higher risk groups. But if we set tape -- just set that aside for a second and just think about BIS versus background, what would you say there in terms of looking, particularly at some of the lower patient -- lower risk patient groups, was your sense that there was a decent separation across the different risk strata, if that's the word?

Sure. That's a great question. So actually, when you look at even low-risk population patients. So I think about low-risk studies, meaning more than 50% sentinel lymph node, as an example. The benefits still held actually and it was still clinically significant. So if you look at that example, it was about a 5% rate annualized for no intervention or background versus 1.4% with BIS. Similarly, when you look at low rates of mastectomy, meaning more than 60% of patients receiving BCT, that same benefit held when comparing BIS to the background group. So I think even in low-risk population patients, we're still seeing those benefits.

Great. And then, look, finally for me, just on tape measure on those results there. I mean on the -- just on the surface of it, it looks to me that there might even be a trend towards that being harmful. I mean did you interrogate the stats around that observation? And that's all for me.

Yes. So we looked at tape measure in multiple different ways. And I think it just comes down to the fact that there's such intra- and inter-observer variability. I don't know if there's anything more you can really dive into the studies because when you look at each of these studies and pulling them together, there's not much more we could do. But I think that it is concerning that tape measure clearly is not showing really any benefit and potentially is worse than kind of this background rate.

[Operator Instructions]

Amanda, while we are paused, let me just make a quick statement here. I think what's important to understand about this study is what we're going to do as a business with this study, there's 2 things. First of all, we will be sending this out tomorrow morning U.S. time to every major insurance company we have engaged in. We think this is a critical, critical study with some great results. So we think this is going to begin to accelerate some of the traction we've already started to see with private pay. And then we do know that Dr. Shah is going to be submitting this to the NCCN in the coming weeks. So there's a lot of things we've got going. So this study we've been waiting for, and we're well prepared to start using this study on a number of different fronts.

We have a next question from [ Ralph Katz ], a private investor.

My question is about the exclusion criteria. Of the 144 studies post 2... [Technical Difficulty]

[Operator Instructions] At this time, we are showing no further questions.

Okay. It's too bad about Ralph -- I -- there's no further questions, and I appreciate everybody's time.

[Operator Instructions] Your next question comes from John Hester from Bell Potter.