Chapters Transcript Video 2026 ASCO Breast Cancer Highlights: HER2CLIMB-05 Harold Burstein, MD, PhD, and Adrienne Waks, MD discuss the HER2Climb-05 trial and how it impacts treatment for HER2+ metastatic breast cancer. I'm Doctor Harold Burstein from Dana-Farber Cancer Institute. Thank you for joining us for another episode of our Breast Cancer Breakthroughs where we have been featuring some of the most important data presented at the 2026 ASCO meeting in Chicago. And I'm delighted here today to be joined by Doctor Ada Wax, one of our medical oncologists, and we're gonna be talking about updates on HER2 positive metastatic disease. Thank you for having me, Hal. I am very excited to be making my debut on Breast Cancer Breakthroughs podcast. I want you to know there was a lot of talk about this. We're very excited to have you here. You know, we got your agent involved and everything. It's all going to be good. It's always how I, how I roll. Yeah, absolutely. Um, all right, well, let me take us through for a few minutes some updates that we saw at OSCO from the HER2 Climb05 trial. This is a trial, uh, that we've seen presented before. These were some subgroup updates from the trial. It, uh, looked at the efficacy and safety of the HER2-TKI to catnib compared to placebo combined with Trestu me pertu me HP maintenance in the first line HER2 positive metastatic setting. So this was the schema of the trial. These were patients with newly diagnosed HER2 positive metastatic breast cancer. They're being treated in the first line setting. They complete induction chemotherapy with taxane, so there were no patients who got induction other than ataxane in this trial. Important because there's now widespread use of trastuzumab direxican perhaps in the first line. Exactly. So this trial was done before we would have been using TDXD in the first line. So all these patients got a taxane induction. They didn't progress during their taxane induction along with HP trastuzumab pertuzumab. And then after they dropped the chemotherapy as they entered the maintenance phase, they were randomized to either get just HP given with the placebo, or HP plus to catnib. And then the primary endpoint was PFS. We previously already saw the investigator SSPFS, which is the primary endpoint of the trial, presented. But the data were updated here continue to show a clinically meaningful improvement in median progression free survival. You can see from about 16 up to 25 months in the overall population. So a nice almost 9 month improvement in median PFS. New data that we saw here that actually wasn't in the original presentation or the JCO paper was the overall response rate in the trial. It's very interesting, right, because 15% of patients are still having a response to the HP. Therapy and another 7 or 8% with the addition of the ducatinib. So we don't, you know, it's not really maintenance, is it? It's really controlling the cancer. Yeah, no, I think that that is interesting to see because these patients had all already completed their taxane and gotten, you know, whatever response or stability they were going to get out of that. I'll remind you, we saw, um, and we're pleased to see the same thing in the Pettina trial that for those hormone receptor positive patients who added palbociclib after completing a chemotherapy injection. They also were still getting responses even during the maintenance portion of their therapy. Um, so, uh, there was an increase in response rate. We still saw responses in both arms and the duration of response was also higher for those who are getting the tatinib. So hormone receptor status is increasingly important in metastatic HER2 positive breast cancer because now, especially in this setting, we have the Patina regimen to think about, um, and we now have this option as a maintenance option. So we saw a further breakdown of the efficacy by hormone receptor status at ASCO this year. It was a nice split, about half of the population was hormone receptor negative, half were hormone receptor positive, so they're both very well represented. Um, we saw the improvement in PFS with the ducatinib in both hormone receptor subgroups. Um, although you can see that the absolute benefit or the absolute sort of addition of Additional months in the tucatinib arm was a little bit more pronounced, about 12 months added in the hormone receptor negative arm versus about 6 or 7 months added in the hormone. So the patients in the hormones that are positive probably were getting anti-estrogen therapy at the same time. It's a perfect question. So let's look at the next slide. Um, because that is a very, very, uh, relevant question as well here. Um, so this is showing just the hormone receptor positive patients in the trial. Of those patients, actually only about half got concurrent endocrine therapy and half did not. That was just a decision that was at investigator discretion. So remember, really importantly, this is not at all a randomized comparison of endocrine therapy and no endocrine therapy. But I think what comes through resoundingly here and is congruent with lots of other data sets that we've seen is that while yes, the ducatinib helps, uh, regardless of concurrent endocrine therapy use, The outcomes in both the placebo and the ticatinib arm are significantly better for the hormone receptor positive patients who are getting the endocrine therapy. So again, not a randomized comparison, but you know, pretty convincing that endocrine therapy is an important part of a maintenance regimen. You look at the control arm there and it makes a strong point. Exactly, exactly. Um, looking at the safety profile across subgroups, so you know, you add an additional agent and you do get some additional toxicity, and that was definitely true here. Um, there were overall more high grade AEs, grade 3+ in the tuatinib arm. You can see that 42% versus 24%. That was mostly driven, um, by hepatic toxicity and I believe also diarrhea, although we don't have that slide, but certainly, uh, transaminitis was more common with the tuatinib as expected. So, uh, thank you for that. Let me just take a step back. For years, we were sort of giving THP therapy, and then we would get a good response and we would stop the chemotherapy component. We would leave the anti-HER2 antibodies going, and often we would introduce an endocrine therapy, and we just kind of did it. Now, it's like a thing. Like we have several data sets. We have PETINA, we have HER2 clam05, looking at maintenance therapy and trying to optimize that. So, uh, obviously, this is progress. We have some real data. Uh, where does this option fit in your mind for patients who had induction with THP, and then we'll come back to the question of the TDXD. Right. I mean, I think for a hormone receptor negative patient where you've done induction with THP, I, I would virtually always at this point based on these data, once we have an FDA approval, be adding to catnib to their maintenance hormone receptor negative, um, because you know it's we just actually see such surprisingly bad outcomes for the hormone receptor negative patients who just get the sort of simple HP maintenance, um, so I would add to catnib maintenance in that setting. For the hormone receptor positive patients, we obviously have this option, but we also have the patina option. Um, and in a hormone receptor positive patient, I would be more inclined to choose patina, honestly, because I think it gives us the best way to get that patient a CDK 46 inhibitor. We know we can give to cat inib in a later line for that patient with a PFS and an OS benefit. We're oncologists, if you're giving 4 drugs, HP, endocrine therapy, and palbociclib, would you throw into catnib on top of that 5 drugs better than 4 drugs? It's a great question. It's true. We tend to head that direction. Um, you know, I think that I would not. I would be concerned about, yeah, exactly. We know that we can use it in a sequential regimen successfully. That's what the original HER2 climb trial told us. And I would be quite worried about toxicity, you know. Combining the two catnib certainly added some toxicity. Adding the pelviciclib also adds some toxicity. I would think, you know, particularly GI toxicity might be potentially like synergistic. Yeah. So in the case of a patient who has induction therapy with TDXD, which is one of the options now, um, do you apply a maintenance strategy or do you just continue the TDXD? Or if you apply a maintenance strategy, where do you think about these products in that space, right? I mean, I think a patient who I chose to do an induction with TDXD, meaning I've stopped at a set number of cycles in the absence of progression. How many cycles should that be? I don't know. Let's say somewhere around 6 months. Um, uh, then if I was transitioning them to a maintenance regimen, absolutely. I would try to optimize their maintenance with, with one of the two current sort of optimal maintenance strategies we have either this or Patina. I am not using a sort of TDXD induction in a widespread across the board way. However, in the first line setting, I mean, I will say at this point we'd really have to be using TDXD plus P induction if we're keeping with the arm of DBO9 that has resulted. Um, and you know, I, I'm just compelled by the fact that that's not the way that the trial was done. Uh, we have good data to give it in a certain fashion in the first line session, uh, setting, great data to give it in a certain fashion, uh, in the second line setting, and to sort of deviate from those data and give it in a different way in the first line. It just feels like something I'm not planning to implement in a terribly widespread way until we have more data. Now, do I look very carefully at that first line patient who I put on TDXD+P and try to see how the tolerability is for them? And if for a tolerability reason, I should switch them to something else? Absolutely. But I don't walk in the room the first day and say, You're going to get this for 6 months and then I'm going to take you off no matter what's happening. Well, excellent discussion. And again, you know, what has really struck me is that, you know, we are now getting some real data on practice habits that many of us have had for a long time. Exciting to see all these drugs moving forward in HER2 positive advanced breast cancer. I'm Doctor Harold Burstein. I've been with Doctor Ada Wax. Thank you for joining us for breast cancer updates and highlights from Dana-Farber Cancer Institute. We look forward to seeing you soon. 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