Table 2.

Summary of clinical studies evaluating tucatinib combination approaches in HER2+ metastatic breast cancer patients with brain metastasis

Treatment(s)	Parameter(s)	Study design and finding(s)
Tucatinib + trastuzumab + capecitabine [47]	OS	To evaluate safety. The OS was 20.7 months with the tucatinib-combination
Tucatinib + T-DMI [77]	mPFS	Phase I dose-escalation study to evaluate effect. The mPFS was 8.2 months
Tucatinib + trastuzumab [78]	MTD	Phase I dose-escalation study to evaluate response. The combination therapy was tolerable and effective in HER2+ breast cancer patients having brain metastases
Tucatinib + capecitabine, tucatinib + trastuzumab, tucatinib + capecitabine + trastuzumab [46]	mPFS	Phase I dose-escalation study to evaluate response. ORR of tucatinib + capecitabine was 83%, tucatinib + trastuzumab was 40%, and tucatinib + capecitabine + trastuzumab was 61%. The mPFS of the triple combination in patients with no brain metastasis was 7.8 months; however, it was 6.7 months in patients with brain metastasis
Tucatinib + trastuzumab + capecitabine [79]	OS	Phase II study to evaluate safety and efficacy. The median OS was 11.9 months and the median time to CNS progression 6.9 months

HER2+ HER2-positive, OS overall survival, T-DMI ado-trastuzumab emtansine, mPFS median progression-free survival, MTD maximum tolerable dose, ORR objective response rate, SD stable disease, CNS central nervous system