Patient Profile 3: Treatment Sequencing in a Patient with metastatic HER2+ Breast Cancer


Shared insight on factors for selecting therapy in a patient with HER2+ metastatic breast cancer progressing through multiple lines of therapy.


Shanu Modi, MD: It sounds like she has refractory disease, and you have now cycled through 4 or 5 lines of therapy. At this point what do you end up giving to her as her next option?

Rena Callahan, MD: At this point, I gave her T-DXd, trastuzumab deruxtecan, and she did not respond.

Shanu Modi, MD: That’s disappointing to hear.

Rena Callahan, MD: Surprising, how often does that happen, right? It was really disappointing.

Shanu Modi, MD: She is someone who probably would have fit the criteria, I don’t know what her liver functions were like at the time, but who could have been a candidate for the phase 2 DESTINY-Breast01 trial, median 5 lines, 6 lines of prior therapy, and almost every single patient on that trial had some benefit. She would have been that one outlier on the left side of waterfall plot; it’s sort of interesting to wonder what’s different about the biology in her disease. You didn’t get any mileage out of that ADC [antibody-drug conjugate]. What did you end up treating her with next?

Rena Callahan, MD: Then I put her on the HER2CLIMB regimen, tucatinib, trastuzumab, and capecitabine, and she did great. She had a great response. At this point, she was also developing some brain metastases, small though, and we treated those with stereotactic radiation, and even after progression when a few more of these popped up, we still treated it, kept her on it, and she did well on it for a while.

Shanu Modi, MD: The interesting thing about patients with HER2-positive breast cancer is they can go on to have multiple lines of therapy. Was there anything else you were entertaining besides tucatinib and capecitabine at that point?

Rena Callahan, MD: At that point, I thought it was the best choice for her. But something that had come up a few times, she was ER [estrogen receptor]-positive and HER2+, and so we had talked about abemaciclib and endocrine therapy, and HER-directed therapy at that time, but chose the HER2CLIMB regimen. Then that came up again later, but maybe too late.

Shanu Modi, MD: It sounds like at further progression you tried some chemotherapy with eribulin and trastuzumab. Ultimately, were you ever able to give a course of endocrine-based treatment to her?

Rena Callahan, MD: Not in any real way. It was one of those situations where she was so sick, chemotherapy wouldn’t have made any sense. But she had a sample of abemaciclib from few months prior and wanted to give it a shot, but it was just very late in her disease course.

Shanu Modi, MD: This is a sobering case. We talk about how many great new options we have that are really active, but the reality is that most patients with metastatic disease are still going to eventually progress. Their disease will progress. We are still in search of treatments for patients with refractory disease even today despite the number of options available.

Transcript edited for clarity.

Related Videos
A panel of 3 experts on breast cancer
A panel of 3 experts on breast cancer
Samilia Obeng-Gyasi, MD, MPH,
Nan Chen, MD
Timothy Yap, MBBS, PhD, FRCP
Parul N Barry, MD,
Erin Frances Cobain, MD
Erin Frances Cobain, MD
Video 6 - "Shared Decision Making and Multidisciplinary Collaboration in the Evolving HR+/HER2- Early-Stage Breast Cancer Landscape"
Manmeet Singh Ahluwalia, MD