Breaking Down Side Effects of Tukysa in HER2+ Breast Cancer

Dr. Erika Hamilton recently discussed her work on the HER2CLIMB05 clinical trial evaluating Tukysa (tucatinib) in combination with Herceptin (trastuzumab) and Perjeta (pertuzumab) in patients with HER2-positive metastatic breast cancer, findings from which were presented at the 2025 San Antonio Breast Cancer Symposium (SABCS), in a comprehensive conversation with CURE.

Hamilton is the Chief Development Officer, Late Phase, as well as Director, Breast Cancer Research, at the Sarah Cannon Research Institute (SCRI). She spoke with CURE’s editor-in-chief, Dr. Joshua K. Sabari, an Assistant Professor in the Department of Medicine at NYU Grossman School of Medicine and Director of High Reliability Organization Initiatives at NYU Langone’s Perlmutter Cancer Center.

Among the topics they discussed was the side effect profile of the drug, which was approved by the U.S. Food and Drug Administration (FDA) in 2020 to treat adults with HER2-positive breast cancer that can’t be removed surgically, or has spread other parts of the body, and who have received one or more prior therapies for metastatic disease.

To watch Hamilton and Sabari’s full conversation, be sure to visit CURE’s YouTube channel.

Dr. Hamilton, what are the side effects of the drug? We know that all therapies, whether they're chemotherapy or targeted therapy, have some side effects.

With tyrosine kinase inhibitors, we immediately think of rash and diarrhea. What's special about [Tukysa] is it's HER2 specific. It's not a general, so it doesn't block HER1 or EGFR, and so we don't get as much rash, we don't get as much diarrhea, but historically, we do get some diarrhea with [Tukysa], and particularly because we've been giving it with capecitabine, which causes diarrhea. So, we did see diarrhea. Dose reductions due to diarrhea was in 6% of patients receiving [Tukysa]. So honestly, not that much. And in fact, 3% of the patients reduced placebo that weren't actually receiving [Tukysa]. So small actual numbers of patients were actually needing a dose reduction. In terms of discontinuation, exceedingly rare, 1.5%, so this really was able to be given frequently.

What we did see was the most common reason for a hold was actually due to hepatic elevations. This was 7.7% of patients had to discontinue due to elevated liver function. This is predominantly AST, ALT, we saw that in HER2CLIMB, the original study. So, you’re definitely going to have to monitor the liver function enzymes, definitely going to have to make sure patients know about strategies for diarrhea, but it tends to really be pretty tolerable there, and we don't see rash with this.

So if you're a patient or a family member getting this medicine and your liver numbers are mildly elevated, how do you counsel patients?

That's a great question. So for very mild elevations, we really don't need to do much. We'll see what the FDA label ultimately says. I imagine it'll mirror HER2CLIMB in the later setting, where we really kind of hold and discontinue with grade 3 (severe elevations). A lot of our patients do have a liver metastases, and so they're even allowed to start this drug at 2.5 times the upper limit of normal, etc. So we don't need to worry about these more mild ones. It's really the ones where we're bumping a little bit higher than that that we need to worry about.

Transcript has been edited for clarity and conciseness.

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