Efficacy and Safety of Human Epidermal Growth Factor Receptor 2 (HER2) Antibody-Drug Conjugates in Solid Tumors Harboring Non-tyrosine Kinase Domain ERBB2 Mutations: A Systematic Review - PubMed
4 hours ago
- #solid tumors
- #non-TKD ERBB2 mutations
- #HER2 ADCs
- ERBB2 (HER2) gene mutations are oncogenic drivers in various solid tumors, with therapeutic focus mainly on tyrosine kinase domain (TKD) alterations.
- Non-TKD ERBB2 mutations occur in extracellular, transmembrane, juxtamembrane, and C-terminal domains, but their response to HER2 antibody-drug conjugates (ADCs) is not well characterized.
- A systematic review following PRISMA 2020 guidelines analyzed clinical studies on HER2 ADC therapy in solid tumors with non-TKD ERBB2 mutations.
- Nine studies were included, with trastuzumab deruxtecan being the most frequently used ADC, showing tumor responses, especially in extracellular and transmembrane/juxtamembrane domain mutations.
- Limited evidence supports ADC efficacy in C-terminal domain mutations, primarily from case reports.
- Interstitial lung disease (ILD)/pneumonitis was reported in some patients, including severe cases, but no fatal events were noted.
- HER2 ADCs show meaningful antitumor activity in non-TKD ERBB2-mutated solid tumors, particularly in extracellular and transmembrane/juxtamembrane domains, but benefits vary across mutation domains.
- Study heterogeneity and lack of mutation-domain-stratified outcome reporting limit interpretation, calling for prospective studies to better define ADC roles in non-TKD ERBB2-mutated cancers.