HER2+ Metastatic Breast Cancer: Safety Data With T-DXd


Homing in on trastuzumab deruxtecan, T-DXd, expert panelists review recent safety data in the setting of HER2+ metastatic breast cancer.


Andrew Seidman, MD: At ASCO [American Society of Clinical Oncology Annual Meeting] this year, we had some updates from Erika Hamilton [MD] on safety from DESTINY-Breast03. I’ll frame the discussion with a case. This is a real case from my practice of a patient who has a diffusing capacity of 73% of predicted. Not a smoker, not really sure why. Could be some interstitial pneumonitis from a drug that she had years ago, but there was no obvious event. Do I need to get a pulmonary function test before I give this drug? [Whom] should I not give it to?

Stephanie Graff, MD: The problem is that we just don’t know with trastuzumab deruxtecan [T-DXd] who is going to develop interstitial lung disease. The updated safety data from DESTINY-Breast03 was that 10.9% of patients developed interstitial lung disease and the vast majority of that was grade I and grade II. For those of you that don’t live and breathe the clinical trial adverse event profiles, grade I interstitial lung disease means infiltrates on a chest x-ray with no symptoms, which for the record in a global pandemic of lung diseases is 10% grade I pneumonitis. So it’s hard to even put that into context. As the DESTINY-Breast portfolio has evolved, the rate of interstitial lung disease has gotten better, certainly not worse, which is maybe a testament to our learning curve as investigators [and] as a medical oncology community with the drug.

Globally, I feel like Dr Hamilton’s presentation really supported that trastuzumab deruxtecan is very well tolerated and very safe. The other signals with trastuzumab deruxtecan are cytopenias, anemia, thrombocytopenia, and then about 6% or 7% risk of nausea with trastuzumab deruxtecan, although patients in the trial were not prophylaxed with nausea. It probably, with that rate of nausea, warrants higher rates of emetogenic potential and appropriate prophylaxis therapy for nausea. In terms of your patient, I think it’s a risk-benefit discussion with the patient on what you want to consider and try. I certainly would be monitoring those patients more carefully. I similarly have had a patient with pericardial effusion, pleural effusion with significant shortness of breath at presentation, who I ultimately treated with [trastuzumab deruxtecan] and it all dried up and she [INAUDIBLE].

William Gradishar, MD: I think that’s one of the misconceptions that we sometimes dispel. We have heard this on the virtual world we have existed in [over] the last year, talking to physicians in the community [about how] if their patients have a bunch of lung metastasis or something, you shouldn’t give it. But it’s the opposite. When you have bulky visceral disease, those are the patients most likely to benefit.

Andrew Seidman, MD: VK, when your patient comes back for her first 3-month scan and her metastatic pulmonary nodules or liver disease has improved but now you see asymptomatic patchy ground-glass opacities, what is your maneuver? Do you just push on? Do you give her some prednisone? What is your approach?

Vijayakrishna Gadi, MD, PhD: I try to follow the guidelines in this situation, which is [that] you would probably want to hold the drug to give it an opportunity to resolve. You may not have to [start] the steroids right away and then maybe consider rechallenging. Anything more than that, though, I think it’s really important to follow the guidelines. I am going to throw out a hypothesis, which is, in the earlier study when we saw so many deaths with this molecule and even more severe pulmonary toxicity, I think we were so inclined in that when you see a patient, nothing is working, [they have had] 7 lines of therapy, when you give something and it’s working, then we’re going to dismiss this small infiltrate. I think that’s where we get in trouble. So being respectful of that I think is very important, and pulling your punches and letting that recover [are] probably the right move.

Stephanie Graff, MD: In my conversations with many of the DESTINY-Breast03 investigators, I was one of them, many of us used Medrol Dosepak [methylprednisolone] when we needed to get patients through mild infiltrates and rechallenged.

Andrew Seidman, MD: Tiffany, any other thoughts on T-DXd before we move on? Because I am going to pick your brain about brain metastasis next.

Tiffany Traina, MD: I think my colleagues summed it up beautifully. The drug is highly active as you talk about response rates. In [DESTINY-Breast03], it was around 80-something percent, so when we use it, we expect people to feel better as result of [the] disease being under good control.

Transcript edited for clarity.

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