Therapies targeting HER2 have become a standard of care (SOC) treatment for patients with HR+ HER2+ breast cancer; however, resistance can arise through multiple mechanisms. Those who progress on HER2 therapies may benefit from further treatment with a combination of cytotoxic chemotherapy and additional HER2-directed agents. Initial results from the monarcHER trial found that abemaciclib, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, combined with the HER2-targeting immunotherapeutic trastuzumab and the selective estrogen receptor degrader fulvestrant improved progression free survival (PFS) in patients with HR+ HER2+ advanced breast cancer (ABC) compared to chemotherapy plus trastuzumab. In this update to the phase II monarcHER trial, Tolaney and colleagues assessed overall survival (OS) in patients with HR+ HER2+ with ABC treated with abemaciclib, trastuzumab, and fulvestrant (Arm A), abemaciclib plus trastuzumab (Arm B), or SOC chemotherapy plus trastuzumab (Arm C). The authors report a median OS of 31.1...

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