Tucatinib added to trastuzumab and pertuzumab maintenance therapy showed a clinically manageable safety profile in the phase 3 HER2CLIMB-05 trial, a new analysis that will be presented at the 2026 American Society of Clinical Oncology Annual Meeting. The data add to the case for the regimen in HER2-positive metastatic breast cancer after induction treatment.

The safety analysis included 326 patients who received tucatinib and 324 who received placebo, with median treatment durations of 17.1 months and 15.5 months, respectively. Veronique C. Diéras helped conduct the analysis, which was designed around patients whose disease had not progressed after a taxane plus trastuzumab and pertuzumab.

That matters because the regimen is being evaluated as first-line maintenance therapy, where tolerance over time can matter as much as tumor control. In the study, tucatinib was given at 300 mg twice daily with trastuzumab and pertuzumab, and the trial identifier is NCT05132582.

The safety profile was not clean in the way a press release might imply. Grade 3 or higher treatment-emergent adverse events were more common with tucatinib than with placebo, at 42.3% versus 24.4%, and the most common severe events in the tucatinib arm were elevated alanine aminotransferase at 13.5% and aspartate aminotransferase at 7.1%. Hepatic events were also more frequent with tucatinib, at 43.6% versus 15.7%, while diarrhea occurred in 72.7% of patients on tucatinib compared with 51.2% on placebo.

Still, most hepatic and diarrhea events were managed with dose changes or stopping treatment, and no treatment-related deaths were seen. Tucatinib was discontinued because of treatment-emergent adverse events in 13.5% of patients overall, including 7.7% because of hepatic events and 1.5% because of diarrhea. Cardiac treatment-emergent adverse events were reported in 4.3% of the tucatinib group and 6.2% of the placebo group, and no new safety signals were observed.

Among patients with diarrhea, antidiarrheal medication was used in 57.7% of the tucatinib group and 29.9% of the placebo group, with loperamide the most common agent. Investigators said the addition of tucatinib to first-line trastuzumab and pertuzumab maintenance therapy may be an effective option for HER2-positive metastatic breast cancer with a clinically manageable safety profile, but the practical balance between that safety profile and the previously reported progression-free survival benefit will be weighed more fully when the findings are presented in 2026.