Chapters Transcript Video 2026 ASCO Breast Cancer Highlights: Neo-Healer Harold Burstein, MD, PhD, and Adrienne Waks, MD discuss the new Neo-Healer trial in HER2+ breast cancer. I'm Doctor Harold Burstein from Dana-Farber Cancer Institute. Thank you for joining us for our ongoing discussion of breast cancer breakthroughs where we are featuring some of the exciting data presented at the 2026 ASCO meeting in Chicago. Today, I'm with Doctor Ada Wax. We're gonna be talking about the Neo-HALer trial. Let me just say at the outset, one of the exciting things at ASCO was a huge influx of Chinese developed and executed clinical trials. This one is one of them. Uh, I think a lot of people really were um impressed at the number of studies coming out of China right now. I was impressed with the number of studies coming out of China, and I was also very impressed by how quickly they're able to accrue these studies. This study accrued 500 some odd patients in 8 months. Exactly. If you, if you sort of try to do the division and break down across breast cancer subtypes across metastatic and early stage setting, the monthly accrual on the trials that they're presenting, it's, it's astounding. It's a very rapid. Tell us about the study here. Um, all right, so the neohealer trial was one of the early stage HER2 positive oral presentations at OSCO. Um, let me go right to the schema. So this was a trial for stage 2 to 3 early stage HER2 positive breast cancer. Patients getting treated in the neoadjuvant setting, as is the standard of care. The control arm was taxi trastuzumab pertuzumab, so THP, uh, for 6 cycles, very standard regimen, and the investigator had the choice. Of whether or not to add carboplatin, and that was true in both arms of the trial. There was investigator discretion about the addition of carboplatin. Obviously a ton of controversy about the role and the activity of carboplatin in early stage HER2 positive. Is there really that much controversy? I mean, for a stage 2 or 3 breast cancer, are you not routinely adding carboplatin? I think there's a lot of controversy. Tell me about the controversy. I mean, I think it's now completely clear it's been established in two randomized. Phase 3 trials, both conducted in Asia to your earlier point, um, it's been established in both of those trials that carboplatin added to a taxane HP backbone does not improve PCR rates like beyond a shadow of a doubt in those two trials does not improve PCR rates. The problem is, and the reason that I think it's a controversy, not an answered question, is that PCR is not a good enough endpoint. You know, we need long term outcome data. We don't have that with a platinum sparing regimen yet. Fair enough. All right. We'll come back to that. Um, so yes, also very ripe for discussion, but I think reflecting that the status of those data in this trial, you could choose in either arm to add your carbo or not. So the, uh, control arm was THP times 6 plus or minus carbo. The experimental arm, the comparator arm was this interesting novel combination where instead of the HP they used uh a drug called anbeidumab, which is a bi-specific, uh, biparatopic. Antibody against two different epitopes on HER2. So not an antibody drug conjugate. This is just two, it binds to two different epitopes of this, uh, the antibody binds to two different epitopes, uh, but there's no chemotherapy. There's no cytotoxic components. So it's a bi-specific antibody without a conjugated cytotoxic. Um, it's, uh, you know, in its design, I don't know the actual chemical structure, similar to, uh, the drug xanidatumab. That we have in many clinical trials. So conceptually you're thinking this is trastuzumab plus pertuzumab in one, like that Goober's jelly thing where they put peanut butter and jelly in the same jar. That's exactly right. That was quite an innovation, um, and that's exactly right. And there's pre-clinical data that's, you know, I think pretty strong and convincing that in terms of the activity, this biperatopic design may actually be more active than H+. Because of the way it sort of clusters the HER2 on the cell surface and clumps them together and it's a better inhibitor of the signaling, etc. etc. So that's what the anbaninumab is. And then they combined, uh, the anbaninumab with another novel molecule called HB 1801, which is an albumin-bound docetaxel. So we're used to talking about albumin-bound paclitaxel, but this is albumin-bound docetaxel. So a different taxing backbone and a different approach to the dual HER2 blockade, and then a primary endpoint of PCR. Um, I'll skip through the baseline characteristics relatively quickly, but it was a moderate to high risk population as you'd expect in any adjuvant trial. Um, and the trial met its primary endpoint. There was a significant improvement in PCR rate from about 51% up to 62%. Um, so we don't know which drug, uh, or both was responsible for this improvement, but certainly, uh, with respect to the endpoint of PCR, the novel regimen was more active. So, um Let me ask you a few things. Uh, on the one hand, this is a bit of a hypothetical discussion in that it is not expected that anytime soon these drugs will be available in the US market or Western Europe. Actually, Rick Pastor was speaking to Harvard Medical School this afternoon, and, um, you know, there are questions about whether all China studies could be approvable at some point based on the data, but it seems like the, if I was looking at this at the FDA, I would say, well, where's the standard comparison arm? But let's assume that The drugs were available. How does this compare to other options and what is your preferred option right now? I'm gonna start with the intermediate risk cancer, like a 3 centimeter node negative cancer versus say stage 3 locally advanced disease. What, what are you using as your first? Let's go to the Well, actually, let's do that first. Just today, stage 2 intermediate risk, what would you give as the neoadjuvant program for HER2 positive breast cancer? Yeah, it's a, it's a hard question at the moment. So, you know, for a small clinical T2N0 at the moment, which I wouldn't necessarily even call it, I would call that sort of low, low risk, you know, low intermediate risk, not node positive. Um, at this point I would give THP plus or minus carbo. You know, we talked about the carbo pros and cons, uh, at the beginning. Um, I still would add it on the basis of its, uh, robust long term outcome data for a younger. Patient or somebody who you know wanted to get absolutely everything belt and suspenders and I would omit it for an older patient, somebody who was more chemo averse so THP plus minus carbo for a clinical T2 and 0 would still be my current and for locally advanced stage 3 disease, you know, nodes, bigger tumor, inflammatory breast cancer. At this point for pretty much anybody node positive and certainly locally advanced node convincingly high risk, I would give the Destiny Breast 11 regimen. OK, so you're going to TDXD with TDXD and then THP for 8 cycles total. TDXD then THB, right? OK, uh, so in that study, uh, in DB11, the PCR rate was higher than we saw in this trial numerically. All the caveats about cross-study comparisons, um, but it's a pretty high bar at this point, uh, based on DB11 for that TDXD THP regimen. Do you think that this is gonna be able to supplant that were these drugs immediately available? I doubt it, honestly. Um, I mean, you're right, with all the caveats of cross trial comparison, the PCR rate in the, um, in the experimental arm, the TBXDTHPR of DB11 was 67%. So it's numerically a bit higher than it was here. And I do think that's notable, especially because DB11 enrolled a particularly high. Group of patients. I'd have to compare the eligible patient populations here, honestly, but I would bet that they were even a little bit higher risk than these patients because DB11 was particularly high risk. So, you know, getting to such a high PCR rate is impressive. But honestly, when you look at PCR rates in trials like Helen 06 and NEOCARP, 6 cycles of Of THP, um, and one of those given with non-pclitaxel instead of Paclitaxel because we know the albumin bound bumps up PCR rate a little bit, but that's been established in other trials, um, you know, you also get to 65% PCR rate. So TDXD based regimens aren't the only way to get to such a high PCR rate. But, uh, you know, I think that the drug is so very, uh, active in general in HER2 positive breast cancer. And generally since the toxicity looked actually so surprisingly good in DB11, it was less toxic than ACTHP. Those would be my reasons for giving it over something like this. So you made a point earlier about not having the long term follow up data. We obviously don't have that for DB11 either. So we have DB11 data in the metastatic setting. We have it in the DBO5 residual disease setting. I think that makes many of us very comfortable with the idea of using it upfront, but You know, do you, do you ever pause and say, well, actually we don't really know what the impact is going to be on the recurrence free or even overall survival, and therefore it's still an experimental option? Yeah, I think that's a great question and point, you know, I think. Because we have early stage data in the adjuvant setting for TDXD from DBO5 showing us like beyond a shadow of a doubt that that's more active in a high risk population than the compared arm of TDM1, you know, we do have long term outcome data for TDXD in early stage breast cancer, um, so I feel a little bit more comfortable because of that. But then the asterisk is that's with 14 cycles and not with 4 cycles exactly. So what I don't feel 100% confident. In, and I don't think anybody should, is that 4 cycles is enough to get you that long-term outcome benefit. It certainly may be, but I'm not 100% sure. But, you know, nothing is tying your hands if you give 4 cycles in the neoadjuvant setting, and you don't quite get that patient to a PCR. I don't think it's tying your hands from giving them some more cycles in the adjuvant setting, if you feel that that's what they need. It's just potentially not the right thing to do because you might want to switch to a different agent when a patient has Displayed some resistance. Got it. All right, well, we're learning a lot still about neoadjuvant approaches for HER2 positive breast cancer. Uh, sounds like you've got a set in your own mind for intermediate risk, mostly THP induction and then TDXD based, uh, a la DB11 for the higher risk. I've been talking to Doctor Ada Wax. I'm Doctor Hal Burstein from Dana-Farber Cancer Institute. Thank you for joining us for this program today and stay tuned. There'll be more to come as the data keep rolling in. Published August 22, 2026 Created by Related Presenters Harold Burstein, MD, PhD Medical Oncology View Full Profile Adrienne Waks, MD Medical Oncology View full profile
