Ongoing Second-Line Trials in Patients with HER2+ mBC and Expert Clinical Perspective


Panelists briefly touch on ongoing trials of second-line tucatinib combination therapy, including HER2CLIMB-02 and HER2CLIMB-05, in patients with or without brain metastases, and offer their clinical perspective which second-line regimens they typically recommend for their patients with HER2+ mBC.


Sara Hurvitz, MD: The field has certainly changed in the last 5 years, hasn’t it?

Heather McArthur, MD: Absolutely.

Sara Hurvitz, MD: And it’s going to continue changing potentially from studies like HER2CLIMB-02. Do you want to tell us about that, Virginia?

Virginia G. Kaklamani, MD, DSc: Yes. So, that again is meant as a second-line trial. Again, it was thought of before T-DXd [trastuzumab deruxtecan], but this combines T-DM1 [trastuzumab emtansine], which was up until recently our standard second-line option with tucatinib. And I think the benefit of this is to hopefully delay, or even treat in many cases, CNS [central nervous system] disease. We know from the early-stage setting that when you give T-DM1 to patients that don’t have a pCR [pathological complete response], you’re improving outcomes except for brain metastases. So this is really something that we struggle with. Hopefully this trial is accrued. It’s going to be presented soon hopefully at a conference and we’ll have our answer. And the benefit of this might be the delay or treatment of brain metastases.

Sara Hurvitz, MD: It would be a great win for patients. And again, as you said, it’s being evaluated in both the early-stage setting and in this setting so it could definitely be practice changing. And then we have the HER2CLIMB-05 study of T-DXd with tucatinib. And I think there’s a DESTINY study with T-DXd and tucatinib. So we’re going to see some more tucatinib combination data forthcoming. Melinda, your go-to regimen, I take it’s based on the DESTINY-Breast03 in the second-line setting?

Melinda L. Telli, MD: It’s T-DXd. I think in the patient case that you presented with progressing brain metastasis, we do have probably higher-level evidence for that group from [the] HER2CLIMB study. The overall efficacy with T-DXd, I really think it is the standard for second line.

Sara Hurvitz, MD: And Debu, if you have a patient progressing only in the brain, no extracranial metastases after first-line THP [docetaxel, trastuzumab, pertuzumab], how do you think through T-DXd as second line vs the HER2CLIMB regimen?

Debu Tripathy, MD: Well, my thinking on that, and I think many people, is evolving over time. The current guidelines really are not to change systemic therapy if there is no progression systemically. But now that we have more active drugs and the natural history, we know that over time is a higher and higher ongoing risk of progressive brain metastases. I’m starting to consider in some patients, not all of them, and I really discuss the pros and cons of making a change in their therapy. Generally, T-DXd, because I think the systemic control is going to be better, or HER2CLIMB, if the patient may have underlying lung disease and I’m concerned about ILD [interstitial lung disease]. I am starting to selectively now change systemic therapy in those situations.

Transcript edited for clarity.

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