How we treat patients with metastatic HER2-positive breast cancer

• Published in: ESMO open 2022-02, Vol.7 (1), p.100343-100343, Article 100343
• Main Authors: Nader-Marta, G., Martins-Branco, D., de Azambuja, E.
• Format: Article
• Language: English
• Subjects: Ado-Trastuzumab Emtansine; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; breast neoplasms; Breast Neoplasms - pathology; Female; HER-2 protein; Humans; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Receptor, ErbB-2 - therapeutic use; Review; trastuzumab deruxtecan; trastuzumab duocarmazine
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2021.100343

HER2-positive breast cancer represents 15%-20% of breast malignancies and is characterized by an aggressive behavior and high recurrence rates. Anti-HER2-directed agents represent the mainstay of treatment of patients with HER2-positive metastatic breast cancer (MBC). In this review we propose a treatment algorithm for patients with HER2-positive MBC based on the currently available literature on the topic. The combination of trastuzumab, pertuzumab and a taxane (THP) remains the preferred first-line therapy in most scenarios. Results of trials recently presented at the European Society for Medical Oncology (ESMO) Congress 2021 might have direct clinical impact in the second- and later-line settings. The randomized DESTINY-BREAST03 study compared trastuzumab deruxtecan (T-DXd) with trastuzumab emtansine (T-DM1) in patients previously treated with trastuzumab and a taxane. T-DXd significantly improved progression-free survival and showed a trend towards improved overall survival, establishing this agent as preferred second-line therapy. Treatment with T-DM1, or the combination of tucatinib, trastuzumab and capecitabine, are considered reasonable options after second-line therapy. For subsequent lines, trastuzumab duocarmazine, neratinib plus capecitabine or the continuation of trastuzumab with different chemotherapy partners are valid options. For patients experiencing disease relapse up to 6 months after completion of adjuvant therapy, as well as for those relapsing within 12 months from the completion of pertuzumab-based adjuvant treatment, we recommend T-DXd as preferred first-line option. For those relapsing between 6 and 12 months after non-pertuzumab-based adjuvant treatment, we recommend first-line THP. Finally, for patients with active brain metastasis, tucatinib-based combination represents a suitable second-line option. •Treatment landscape for patients with HER2-positive metastatic breast cancer is rapidly evolving.•Trastuzumab deruxtecan improved outcomes in comparison with T-DM1 and should now be the preferred second-line therapy.•T-DM1 and tucatinib-based therapy are valid third-line options.•Toxicity profile should be taken into account when considering different later-line treatment options.