Chapters Transcript Video ESMO25 Breast Cancer Highlights: Antibody-Drug Conjugates Harold Burstein, MD, PhD, and Ilana Schlam, MD, MPH, discuss OptiTROP-Breast02 and other trials investigating antibody-drug conjugates (ADCs). We've been talking about antibody drug conjugates and highlights in phase 3 studies presented at ESO 2025 in Berlin. We just finished discussing about new data for these ADCs in advanced triple negative breast cancer in the first line setting now. We're going to pivot and talk about a novel ADC in the treatment of ER positive metastatic breast cancer to help us with that discussion, Dr. Alanna Slam. Ilana, tell us a little bit about the Optitrop breast 02 trial and what population they were looking at here. Thank you very much. Uh, this trial was a phase 3 study in which patients with hormone receptor positive HER2 negative breast cancer that had received 1 to 4 prior lines of treatment were randomized 1 to 1 to receive SATMT versus chemotherapy of physicians' choice. This ABC is a little bit different from s Saitosomegovetican. It has the same antibody that target strop two, but a different payload that also is a TOA1 inhibitor but it's slightly different. So a lot of these drugs we're hearing about these days are TOPO1 inhibitors. They all have fundamentally similar exotecan and reno Tan type drugs, but here we're talking about another anti-Trope 2 antibody with that same payload, and this study was largely done in China, I believe that's where the drug has had its initial development, though it's been in licensed by some US companies. So the schema here is shown on this slide, um, obviously it's a 1 to 1 randomization to sack TMT versus the standards of care. What were the chemotherapy options patients could get? So, patients received a rubilin, epzytabine, jepzyabine or ytabine or bilin or Ein and everyone has had to have a prior CDK and a taxxan. So it's an important thing. They had at least one line of prior chemotherapy and they'd all had a CDK 46 inhibitor, so perhaps a more. treated patient population than we saw in some other studies in recent years. So let's look at the top line result here. Here's the progression free survival curves. Tell us what was seen. So we saw that double of the PFS from 4 to 8 months, which was statistically significant, so exciting findings. So clearly better than the existing options of chemotherapy in this more refractory population. Any particular side effects that are distinctive to stuzumab for remotecan? So the most common side effects noted were cytopenias, particularly neutropenia and anemia, fatigue, so somewhat similar to what we see with salvia. And does this drug seem to have the pneumonitis risk that we see with some other ADCs? We do not see it as much as we see it on TDXD. So you just mentioned TDXD. So I've sort of made this table here and a moment ago we were talking about the right hand side with triple negative disease. Now let's talk about the middle panel with ER positive disease. We've seen data from Destiny Breast 06 for Trestuzumabdoxticine in the first line. By my count there are now 4 ADC type trials in. Second line or beyond for ER positive breast cancer DBO4 rope on breast01, which uses the um data potumaboxacan drug and there's an approval for it. uh Tropic 02, which was with Satuzumab Govi Tan also approved and finally now stuzumab torimo Tan is this um. Is there one way to choose one of these drugs right now, or do you have a preferred approach in first line versus second line utilization of these drugs? So, we have now many options. I think for patients that have HER2 low or ultra low breast cancer, um, I tend to choose TDXD first. For patients with higher disease burden, I think for patients that are asymptomatic of Low low burden of disease, I still think cytabine or other chemos are reasonable, but if I'm going to move to an ABC, I tend to do TDXD first for that patient population for the small amount of patients that are here to know or that have prior um ABC. I think it's a discussion about the toxicity profile what. Available in clinic here and patient preferences, for example, scheduling is different between data and sassy and things like that that patient preference to consider. That makes a lot of sense. Um, in your mind, um, when you think about a patient, uh, getting ADC based therapy in first line or second line, um, do you think that there is benefit in treating them again with an ADC if they've progressed on one of those in first or second line? Yeah, so that's a great question. We know from retrospective studies that the duration, the PFS with the second ADC tends to be very short, but hopefully we'll answer some of these questions with prospective studies like uh T3DXT and Dana Garrido Castro is leading here to really get answers about sequencing of ADCs in the clinic. I think it depends. Sometimes I put some chemo in between ABCs and in some patients, I just switch ADC. really varies. Yeah, I mean, we're certainly, I gotta be honest, we're giving a lot of multi-line ADC therapy, I would say, and I'm still of a mixed mind about whether that really is helpful. Occasionally we see a patient who seems to do really well, um, but a lot of the time that second ADC, perhaps because the chemotherapy payloads are so fundamentally similar, doesn't seem to change things all that much, but it sure looks like ADCs are here to stay for the time being. Great. So we've been talking about ADCs and ER positive breast cancer, uh, another drug, cetuzumabrimotean joining a growing list of options in the second line setting. More to come in the ADC space, uh, uh, undoubtedly. Thanks very much. Published November 21, 2025 Created by Related Presenters Ilana Schlam, MD, MPH View full profile
