Patient Profile 2: Clinical Utility of the HER2CLIMB Regimen for HER2+ mBC


Centering discussion on a real-world patient profile, subject matter experts discuss use of the HER2CLIMB regimen in HER2+ breast cancer.


Shanu Modi, MD: Let me continue with this case. We left off with her finally needing some radiation but continuing on the T-DM1 [trastuzumab emtansine]. Unfortunately, she continued to have progression in the brain, and isolated progression in the brain. She reached the point where she needed whole-brain radiation and did undertake that, and in spite of that, again a few months later had more progression in the brain. At that point, this is now 2020, there is the availability of tucatinib based on the HER2CLIMB regimen. She was started on the combination of tucatinib plus capecitabine and trastuzumab, and she had a great response in the CNS [central nervous system]. Her response in the CNS lasted a little over 1 year. And this is someone who’d been having rapid progression after radiation, after radiation, after radiation, so it was satisfying to see her disease come under control. However, a little over a year later, again, it was isolated progression in the brain. Intermittently she’d had body scans, PET [positron emission tomography] scans as you’ll see and as you see here, and they were clear. These are tragic cases where we are dealing with progressive CNS disease. At this point, she had a pretty good run with the HER2CLIMB regimen as we heard, and a lot of you have talked about it. Tiffany, maybe I can ask you. Have you had the opportunity to use the HER2CLIMB regimen in patients like this with progressive brain [metastases]?

Tiffany Traina, MD: I have had the opportunity to use the combination, both in patients who had absence of brain metastases before we had clear T-DXd [trastuzumab deruxtecan] data, and as well as patients who’ve had stable treated brain metastases. I haven’t yet had the opportunity fortunately to use it in the setting of progressive brain metastases in the absence of radiation as a treatment choice. But my experience to date with it has been a manageable regimen with awareness of GI [gastrointestinal] toxicity, a lot of education, and nursing support to talk through the management of the pill burdens and the scheduling. I’ve had some success. Your patient story is remarkable given her rapid progression in the CNS alone, to have had that durable response of more than a year was fantastic.

Shanu Modi, MD: Really impressive. I’m going to draw in some of your own research here, and you have been a champion of capecitabine in an alternate schedule than what we typically use, which is 14 days on, 7 days off. When you use or have used the tucatinib regimen, what do you do with your patients? Are you using the HER2CLIMB approach, or are you modifying it based on the work you’ve done here?

Tiffany Traina, MD: That’s a great question. When I use capecitabine, I still use a 7-day-on, 7-day-off schedule based on the data that we’ve published, but also work that our colleague [Andrew] Sideman, [MD, at Memorial Sloan Kettering Cancer Center,] has worked on combining capecitabine with other HER2 TKIs [tyrosine kinase inhibitors] and looking at that 1-week-on, 1-week-off schedule. We’ve found that it mitigates a lot of the GI toxicity. Hand-foot syndrome is still a concern, but it seems to be a more manageable schedule, and we’ve seen benefit and efficacy with it. That still tends to be my capecitabine dosing schedule of choice.

Transcript edited for clarity.

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