Tucatinib

Curigliano G, et al. Annals of Oncology, 2022, 33(3), 321-329.

Tucatinib has demonstrated significant clinical benefits in combination with trastuzumab and capecitabine for patients with HER2-positive (HER2+) metastatic breast cancer, including those with brain metastases. The HER2CLIMB trial, a randomized, double-blind, placebo-controlled study, assessed the long-term efficacy and safety of this combination therapy.
In a cohort of 612 patients, tucatinib addition extended median overall survival (OS) to 24.7 months compared to 19.2 months for the placebo group (HR: 0.73, 95% CI: 0.59-0.90, P = 0.004). Two-year OS rates were 51% and 40% for the tucatinib and placebo groups, respectively. Progression-free survival (PFS) was also significantly improved, with a median duration of 7.6 months versus 4.9 months (HR: 0.57, 95% CI: 0.47-0.70, P < 0.00001).
The survival benefit was consistent across all prespecified subgroups, including patients with brain metastases, highlighting tucatinib's broad therapeutic applicability. Notably, the tucatinib combination exhibited favorable tolerability, with a low discontinuation rate due to adverse events (5.9%), emphasizing its safety in long-term use. These findings affirm tucatinib's role in addressing the unmet needs of HER2+ metastatic breast cancer patients.