Overview
- The randomized, double-blind phase 3 HER2CLIMB-05 trial enrolled 654 patients who had no progression after taxane plus trastuzumab and pertuzumab induction and assigned them to tucatinib or placebo with continued antibody maintenance.
- By investigator assessment, tucatinib extended median progression-free survival to 24.9 months with a hazard ratio of 0.641, corresponding to an 8.6-month gain versus control.
- PFS improvement was consistent across prespecified subgroups, with larger relative benefit in hormone receptor–negative disease and clear benefit in hormone receptor–positive tumors.
- Among patients with baseline brain metastases, median central nervous system progression-free survival was 8.5 months with tucatinib versus 4.3 months with control, a secondary endpoint that investigators described as preliminary.
- Safety was generally manageable, with diarrhea, nausea and elevated liver enzymes most common, though 13.5% discontinued tucatinib due to adverse events and overall survival remains immature.