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

Abstract

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.

Breast Cancer—Epidemiology, Risk Factors, Classification, Prognostic Markers, and Current Treatment Strategies—An Updated Review

“…Biological therapy (targeted therapy) can be provided at every stage of breast therapy– before surgery as neoadjuvant therapy or after surgery as adjuvant therapy. Biological therapy is quite common in HER2-positive breast cancer patients; major drugs include trastuzumab, pertuzumab, trastuzumab deruxtecan, lapatinib, and neratinib [ 295 , 296 , 297 , 298 , 299 ]. Further, the efficacy of angiogenesis inhibitors such as a recombinant humanized monoclonal anti-VEGF antibody (rhuMAb VEGF) or bevacizumab are continuously investigated [ 300 ].…”

Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines

“…Treatment options involving biologic agents with various mechanisms of action are still being developed. These compounds target a number of intracellular processes involved in the spread of HER2-positive BC [ 61 , 62 ]. Tumor suppressor p53 plays an important role in cancer prevention.…”

Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer

“…Fam-trastuzumab deruxtecan (T-DXd) is an ADC that combines trastuzumab to an exatecan derivative (DX-8951) a topoisomerase I inhibitor, through a cleavable tetrapeptide-based linker. In comparison to T-DM1, T-DXd has a higher drug-to-antibody ratio, membrane-permeable payload and a cleavable linker [ 45 , 46 ]. These pharmaceutical properties are essential features of the third generation ADCs and may account for a higher and broader activity of T-DXd.…”