"Positioning of tucatinib in the new clinical scenario of HER2-positive metastatic breast cancer: An Italian and Spanish consensus paper"

Breast. 2024 Aug:76:103742. doi: 10.1016/j.breast.2024.103742. Epub 2024 May 16.

Abstract

Introduction: Advancements in monoclonal antibodies, tyrosine kinase inhibitors, and antibody drug conjugates (ADCs) have notably enhanced outcomes for metastatic HER2-positive breast cancer patients. Despite the expanding treatment options and clinical complexities, determining the optimal sequence of HER2-targeted therapies remains partly uncertain, influenced by various factors.

Methods: To refine HER2-positive metastatic breast cancer management, particularly regarding tucatinib's position, a Steering Committee of leading oncologists in breast cancer care devised a panel of statements via a Delphi approach, focusing on five key topics: general clinical management, therapeutic approaches for patients with HER2-positive breast cancer and brain metastases, treatment sequence, and tucatinib's safety and efficacy.

Results: A total of 29 statements were deliberated, with strong consensus achieved for most. However, no consensus emerged regarding the management of brain progression alongside stable extracranial disease: 48 % advocated for switching to tucatinib, while 53 % favored a stereotactic brain radiotherapy (SBRT) approach if feasible.

Conclusion: The unanimous consensus attained in this Delphi panel, particularly regarding tucatinib's efficacy and safety, underscores oncologists' recognition of its clinical significance based on existing trial data. These findings align closely with current literature, shedding light on areas necessitating further investigation, not thoroughly explored in prior studies. Moreover, the results underscore the scarcity of data on managing brain progression alongside stable extracranial disease, emphasizing the imperative for dedicated research to address these gaps and yield definitive insights.

Keywords: Brain metastases; Breast cancer; HER2; TKI; Tucatinib.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / secondary
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Consensus*
  • Delphi Technique*
  • Female
  • Humans
  • Italy
  • Oxazoles / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines* / therapeutic use
  • Quinazolines* / therapeutic use
  • Receptor, ErbB-2* / metabolism
  • Spain
  • Triazoles / therapeutic use

Substances

  • tucatinib
  • Receptor, ErbB-2
  • Pyridines
  • Quinazolines
  • ERBB2 protein, human
  • Oxazoles
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Triazoles