Multinational phase 3 trial of tucatinib plus trastuzumab emtansine for previously treated HER2-positive locally advanced or metastatic breast cancer

Trastuzumab emtansine (T-DM1) is a standard treatment for previously treated HER2-positive locally advanced or metastatic locally advanced or metastatic breast cancer (la/mBC). The multinational phase 3 HER2CLIMB-02 trial evaluated addition of tucatinib of placebo to T-DM1 in patients with la/mBC after trastuzumab plus a taxane. A total of 463 patients were randomized. After a mediane follow-up duration of 24.4 months, the median progression-free survival was 9.5 months in the tucatinib group versus 7.4 months in the control group (HR 0.76; p=0.0163). The PFS-benefit was seen in all prespecified subgroups, including patients with baseline brain metastases. Interim overall survival data were immature, but favored tucatinib over placebo. Incidences of treatment-emergent adverse events of grade ≥3 or leading to treatment discontinuation were 68.8% versus 41.2% and 22.1% versus 11.6%, respectively, with tucatinib versus placebo. The authors conclude that addition of tucatinib to T-DM1 improved PFS in patients with previously treated la/mBC, including patients with brain metastases, with a manageable safety profile.