Emerging Therapies in HER 2-Positive Metastatic Breast Cancer - Episode 18

HER2+ Breast Cancer: Future Treatment Landscape


Sara A. Hurvitz, MD: Fortunately for patients and unfortunately for clinicians, I think in 5 years we’re going to have even more agents and more therapies available to us. And we’re going to have to select the sequence of agents, hopefully guided by well-designed clinical trials. I do think we’re going to see a shift to the THP [paclitaxel, trastuzumab, pertuzumab] regimen, which is now being used in early-line neoadjuvant and adjuvant settings often, and a shift to the use of T-DM1 [trastuzumab emtansine] in the adjuvant setting. We’re going to see a lot of patients who develop metastatic breast cancer who have already seen those drugs. Naturally, we’re going to see third-line agents move up into the first-line setting. But given that 30% to 40% of our patients, in the United States at least, develop de novo metastatic HER2 [human epidermal growth factor receptor 2]—positive breast cancer, we’ll still be using trastuzumab-pertuzumab and T-DM1.

I think in 5 years, we’re going to start to see phase III evidence that may challenge the current positions in the frontline and second-line settings. We might see DS-8201 [trastuzumab deruxtecan] in the first line or second line. We might see tucatinib in 1 of these lines. I’m most excited actually to explore whether tucatinib can mitigate or prevent the development of CNS [central nervous system] metastases. My hope—and it’s quite a high hope, because it requires 2 companies coming together—would be that we would see a combination of something like DS-8201 with tucatinib, taking the efficacy strengths of both molecules to help improve outcomes for patients.

William J. Gradishar, MD: In five years, we’re likely to have new strategies to treat breast cancer broadly and HER2-positive disease specifically. I anticipate that the drugs we talked about today will, at least many of them, be approved. One of the things that inevitably happens as you develop drugs is that the goal is always to move them up in the algorithm. In other words, they’re pretty traditionally developed in metastatic disease, and then they start moving toward earlier in metastatic disease. Where everybody wants to get their drug is in the adjuvant setting for a variety of reasons. There are more patients.

Most important, if they show a significant efficacy in the metastatic disease setting, the question is, can you diminish the number of patients who will ultimately recur? In other words, you’re curing more patients. For all the drugs that we’re talking about—if they’re effective, if they’re approved—there are likely going to be trials looking at them earlier and earlier. And 2 things will come of that. One is, hopefully, there will be fewer patients with metastatic disease, which is a good thing. But in those patients who do develop recurrent disease, we’ll have to have new strategies. I think 1 of the things that we talked about earlier is looking at novel combinations of HER2-directed therapy with immune therapy as a way of enhancing our own immune systems to treat cancer.

We will likely continue to have new drugs developed: antibody-drug conjugates, novel TKIs [tyrosine kinase inhibitors], probably even antibodies that are different. We talked about bispecific antibodies earlier. And whether these strategies pan out, we’ll see. But I think that by virtue of moving the existing drugs up, we’re going to have to fill that void with newer drugs, and that’s really the subject of the clinical research that is just starting with some of these compounds.

Transcript Edited for Clarity