Patient Profile 2: 3L Therapy for Triple-Positive mBC


Before closing out their discussion on the second patient profile, experts review third-line treatment selection for triple-positive metastatic breast cancer.


Neil Iyengar, MD: [This patient] sustained her response. It was a durable response, for about a year. In early 2022, unfortunately, we found progression with new bone metastases and a new liver lesion. She has viscerally driven disease. We scanned her brain again. This time, we did see new subcentimeter lesions, particularly in the left parietal region. These were very small, but were interpreted by the radiologist as probable metastases. She was asymptomatic, and of course we had her see our radiation-oncologist and neurosurgeon as well.

At that point, we had a very interesting discussion about whether she warranted local therapy or if we should go on tucatinib [Tukysa]–based therapy in the third-line setting. Based on some of the data that you mentioned, which Nancy Lynn presented about the intracranial activity of tucatinib, in this asymptomatic patient with very tiny lesions, I felt comfortable going straight to a tucatinib-based regimen in the third-line setting and holding off on radiation. We certainly had the SRS [stereotactic radiosurgery] discussion with this patient, and she preferred to hold off and see how well she did with tucatinib. That’s what we have her on: tucatinib, capecitabine,and Herceptin [trastuzumab] in the third-line setting. We recently started that, so our fingers are crossed for her.

Milana Dolezal, MD, MSci: Those are all very good points. We can translate from our lung cancer world in terms of if a patient has asymptomatic brain metastases. We know that TKI [tyrosine kinase inhibitor] is going to get up there, and often we’ll repeat another MRI of the brain 6 to 8 weeks later after starting a TKI-based regimen just to see what’s happening. Are those lesions progressing? Are they stable? A different patient—not the 1 I discussed—had brain metastases that have decreased in size substantially as an asymptomatic patient. We feel much more comfortable doing that now, and we don’t know survival data in terms of continuing to do gamma knife and SRS. We do know that over time, the cognitive defects from brain radiation in these patients, who are living much longer, can be pretty significant in terms of their short-term memory loss and long-term memory issues. That’s totally appropriate, and I have my fingers crossed for her too.

We have great phase 3 survival data from HER2CLIMB, as you alluded to. She’s not in visceral crisis. The only other comment is back to the NALA trial and looking at the ER [estrogen receptor]–HER2 [human epidermal growth factor receptor 2] cross-resistance. I wouldn’t necessarily take her off HER2CLIMB and switch her, but given that cross talk, that could be something to consider down the line. The bone metastases progression, despite being on bone-modifying agents, is probably a little more estrogen receptor and hormone receptor driven. That’s going somewhat unchecked in that case.

Neil Iyengar, MD: Absolutely. Great point. That’s certainly something we have in our back pocket for future lines of therapy.

Transcript edited for clarity.

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