Phase 1b-2 trial of tucatinib, letrozole, and palbociclib for previously treated HR-positive, HER2-positive metastatic breast cancer

In breast cancer, the cyclin D1-CDK4/6 complex can cause resistance to antihormonal and HER2-targeted agents. The multicenter phase 1b-2 TLP trial evaluated the HER2 inhibitor tucatinib, the aromatase inhibitor letrozole, and the CDK4/6 inhibitor palbociclib (TLP combination) for previously treated HR-positive, HER2-positive metastatic breast cancer (HR+/HER2+ mBC). The combination was safe and tolerable, and showed excellent efficacy for an all-oral chemotherapy-free regimen.