A Review of Fam-Trastuzumab Deruxtecan-nxki in HER2-Positive Breast Cancer

Objective: To review the pharmacology, efficacy, and safety of antibody-drug conjugate fam-trastuzumab deruxtecan-nxki in the treatment of advanced, unresectable, or metastatic breast cancer. Data Sources: Relevant information was identified through a MEDLINE/PubMed (January 2015 to December 2020) literature search. The new drug application, prescribing information, clinical practice guideline, and abstracts from scientific meetings were also reviewed. Study Selection and Data Extraction: The literature search was limited to human studies published in the English language. All studies evaluating the pharmacology, efficacy, or safety of fam-trastuzumab deruxtecan-nxki for breast cancer were included. Data Synthesis: Fam-trastuzumab deruxtecan-nxki is composed of an anti–human epidermal growth factor receptor 2 (HER2) antibody and topoisomerase I inhibitor (DXd), which causes DNA damage and apoptotic cell death. Major phase I and phase II clinical trials established the efficacy and safety of fam-trastuzumab deruxtecan-nxki for treatment of HER2-positive advanced, unresectable, or metastatic breast cancers that are refractory or intolerant to standard treatment. In these trials, the response rate was 60.9% (95% CI = 53.4-68.0) Common adverse effects included fatigue, nausea, vomiting, decreased appetite, constipation, diarrhea, alopecia, neutropenia, anemia, and thrombocytopenia. Serious adverse effects included interstitial lung disease or pneumonia, febrile neutropenia, left ventricular dysfunction, and embryo-fetal toxicity. Relevance to Patient Care and Clinical Practice: Fam-trastuzumab deruxtecan-nxki is an option for HER2-positive breast cancer following 2 previous lines of HER2-targeted therapy. Conclusions: Fam-trastuzumab deruxtecan-nxki is an effective treatment for HER2-positive breast cancer in the metastatic setting, but randomized controlled trials are needed.