Clinical management of adverse events in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine.

In the HER2CLIMB study (NCT02614794), tucatinib in combination with trastuzumab and capecitabine (TTC) significantly improved progression-free survival and overall survival compared with the placebo combination with a manageable safety profile in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). Based on these findings, the TTC regimen was approved by the US Food and Drug Administration in April 2020 for the treatment of patients with HER2+ MBC, including those with brain metastases, after receiving at least 1 prior anti-HER2 therapy in the metastatic setting. Currently, the TTC regimen is the preferred option for third-line treatment in HER2+ MBC and is an option in the second-line setting for patients with brain metastases. As a multidrug regimen, TTC offers enhanced efficacy with dual inhibition of HER2, both extra- and intracellularly, added to the cytotoxic actions of capecitabine. However, some challenges exist with the TTC regimen related to off-target specific drug toxicities and overlapping adverse events (AEs); the most common being diarrhea, liver enzyme elevations, and palmar-plantar erythrodysesthesia. This article aims to describe the clinical presentation of AEs most frequently requiring dose modifications of the TTC regimen and review their clinical management detailed with visual algorithms that incorporate expert medical guidance gained from experience in managing the TTC regimen in routine clinical practice. With the evolving treatment landscape in earlier line settings for HER2+ MBC, patients may now be treated with different first- and second-line therapies from those available when HER2CLIMB was conducted and this may impact its safety profile.