Implementing antibody-drug conjugates (ADCs) in HER2-positive breast cancer: state of the art and future directions.

The development of anti-HER2 agents has been one of the most meaningful advancements in the management of metastatic breast cancer, significantly improving survival outcomes. Despite the efficacy of anti-HER2 monoclonal antibodies, concurrent chemotherapy is still needed to maximize response. Antibo...

Descripción completa

Detalles Bibliográficos
Publicado en:Breast Cancer Research Vol. 23; no. 1; pp. 1 - 12
Autores principales: Ferraro, Emanuela, Drago, Joshua Z., Modi, Shanu
Formato: research review Journal Article
Publicado: BioMed Central 8/11/2021
Acceso en línea:Ver este registro en EBSCOhost
fields @attributes:
  recordID: 1
pdfLink:
plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=151860815&site=ehost-live
header:
  @attributes:
    shortDbName: ccm
    uiTerm: 151860815
    longDbName: CINAHL Complete
    uiTag: AN
  controlInfo:
    bkinfo:
    dissinfo:
    jinfo:
      jid:
        14655411
        8UYJ
      jtl: Breast Cancer Research
      issn: 14655411
      maglogo: N
    pubinfo:
      dt: 8/11/2021
      vid: 23
      iid: 1
      pid: 24147
      pub: BioMed Central
    artinfo:
      ui:
        151860815
        151860815
        NLM34380530
        151860815
        10.1186/s13058-021-01459-y
        NLM34380530
        151860815
      ppf: 1
      ppct: 11
      formats:
        fmt:
          – @attributes:
              type: T
          – @attributes:
              type: P
      tig:
        atl: Implementing antibody-drug conjugates (ADCs) in HER2-positive breast cancer: state of the art and future directions.
      aug:
        au:
          Ferraro, Emanuela
          Drago, Joshua Z.
          Modi, Shanu
        affil: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
      sug:
        subj:
          Breast Neoplasms Drug Therapy
          Antineoplastic Agents Therapeutic Use
          Receptors, Cell Surface Metabolism
          Antibodies Therapeutic Use
          Antibodies Pharmacodynamics
          Central Nervous System Neoplasms Drug Therapy
          Human
          Antibodies Adverse Effects
          Breast Neoplasms Metabolism
          Antineoplastic Agents Adverse Effects
          Antineoplastic Agents Pharmacodynamics
          Central Nervous System Neoplasms
          Female
          Breast Neoplasms Pathology
          Adverse Drug Event
          Receptors, Cell Surface Antagonists and Inhibitors
          Comparative Studies
          Multicenter Studies
          Evaluation Research
          Validation Studies
          Clinical Assessment Tools
          Scales
          Female
      ab: The development of anti-HER2 agents has been one of the most meaningful advancements in the management of metastatic breast cancer, significantly improving survival outcomes. Despite the efficacy of anti-HER2 monoclonal antibodies, concurrent chemotherapy is still needed to maximize response. Antibody-drug conjugates (ADCs) are a class of therapeutics that combines an antigen-specific antibody backbone with a potent cytotoxic payload, resulting in an improved therapeutic index. Two anti-HER2 ADCs have been approved by the FDA with different indications in HER2-positive breast cancer. Ado-trastuzumab emtansine (T-DM1) was the first-in-class HER2-targeting ADC, initially approved in 2013 for metastatic patients who previously received trastuzumab and a taxane, and the label was expanded in 2019 to include adjuvant treatment of high-risk patients with residual disease after neoadjuvant taxane and trastuzumab-based therapy. In 2020, trastuzumab deruxtecan (T-DXd) was the second approved ADC for patients who had received at least 2 lines of anti-HER2-based therapy in the metastatic setting. The success of these two agents has transformed the treatment of HER2-positive breast cancer and has re-energized the field of ADC development. Given their advanced pharmaceutical properties, next-generation HER2-targeted ADCs have the potential to be active beyond traditional HER2-positive breast cancer and may be effective in cells with low expression of HER2 or ERBB2 mutations, opening a spectrum of new possible clinical applications. Ongoing challenges include improving target-specificity, optimizing the toxicity profile, and identifying biomarkers for patient selection. The aim of this review is to summarize the principal molecular, clinical, and safety characteristics of approved and experimental anti-HER2 ADCs, contextualizing the current and future landscape of drug development.
      pubtype: Academic Journal
      doctype:
        research
        review
        Journal Article
      ougenre: Article
    language: English
    refInfo:
    holdings:
      @attributes:
        islocal: N