Treatment Lines for HER2-Positive Metastatic Breast Cancer
Line Therapy
Combination Therapy: Pertuzumab, Trastuzumab, and a Taxane
– Regimen: Pertuzumab (Perjeta), trastuzumab (Herceptin), and a taxane (docetaxel or paclitaxel).
– Dosing:
– Pertuzumab: Initial dose of 840 mg IV, followed by 420 mg IV every 3 weeks.
– Trastuzumab: Initial dose of 8 mg/kg IV, followed by 6 mg/kg IV every 3 weeks.
– Taxane: Docetaxel is typically given at 75-100 mg/m² IV every 3 weeks, or paclitaxel at 80 mg/m² IV weekly.
– Duration: Taxane is administered for at least six cycles, if tolerated, followed by maintenance therapy with pertuzumab and trastuzumab until disease progression or unacceptable toxicity
Second-Line Therapy
Preferred Option: Trastuzumab Deruxtecan (T-DXd)
– Regimen: Trastuzumab deruxtecan (Enhertu).
– Dosing: 5.4 mg/kg IV every 3 weeks.
– Rationale: Based on the DESTINY-Breast03 trial, T-DXd has shown superior efficacy compared to trastuzumab emtansine (T-DM1) in second-line settings
Alternative Options:
– Tucatinib, Capecitabine, and Trastuzumab: Especially in patients with brain metastases.
– Tucatinib: 300 mg orally twice daily.
– Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of a 21-day cycle.
– Trastuzumab: 6 mg/kg IV every 3 weeks after an initial loading dose of 8 mg/kg[1][2].
Third-Line Therapy
Options:
– Trastuzumab Emtansine (T-DM1): If not used in the second line.
– Dosing: 3.6 mg/kg IV every 3 weeks.
– Tucatinib, Capecitabine, and Trastuzumab: If not previously used.
– Trastuzumab Deruxtecan: If not previously used
Later Lines of Therapy
Options:
– Lapatinib and Capecitabine:
– Lapatinib: 1250 mg orally once daily.
– Capecitabine: 1000 mg/m² orally twice daily on days 1-14 of a 21-day cycle.
– Neratinib and Capecitabine:
– Neratinib: 240 mg orally once daily.
– Capecitabine: 750 mg/m² orally twice daily on days 1-14 of a 21-day cycle.
– Margetuximab: An anti-HER2 monoclonal antibody, used in combination with chemotherapy in late-line settings.
– Dosing: 15 mg/kg IV every 3 weeks
Special Considerations
Brain Metastases:
– Tucatinib-based Regimens: Preferred for patients with active brain metastases due to its demonstrated efficacy in this subgroup.
– Local Therapies: Surgical resection, stereotactic radiosurgery, or whole-brain radiotherapy may be considered based on the number, size, and location of brain metastases