Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial

RCT (n=237) found combination of abemaciclib (oral CDK4 and CDK6 inhibitor), fulvestrant and trastuzumab (TT) improved progression-free survival vs. standard-of-care chemotherapy plus TT (8.3 vs. 5.7 months, HR 0.67; 95% CI 0.45–1.00; p=0.051) with an acceptable safety profile.

SPS commentary:

A commentary commends the authors on the design and conduct of a study so clearly underpinned by a robust preclinical rationale, but points out that the study raises several provocative questions. First, it is not clear how much of the benefit seen in efficacy outcomes is because of the dual blockade of oestrogen receptor by fulvestrant and HER2 by trastuzumab. Also further translational work is awaited to define biomarkers that might identify, beyond oestrogen receptor and HER2, which patients are most likely to benefit from a combination of CDK4 and CDK6 inhibition, endocrine therapy, and anti-HER2 treatment. It notes that the key question for the oncologist is whether this regimen can fit into the landscape of emerging therapies in HER2-positive breast cancer. Approvals of neratinib and trastuzumab dexrutecan, and randomised phase 3 data for tucatinib and margetuximab, in addition to the already well established anti-HER2 therapies, mean that multiple questions regarding optimal sequencing, comparative toxicity, and patient preference will arise. It concludes overall that a chemotherapy-free option, with proven efficacy in a heavily pretreated population, is a welcome addition to the treatment options for patients with hormone receptor-positive, HER2-positive breast cancer.


The Lancet Oncology

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