HER2 Positive Metastatic Breast Cancer (HER2+ MBC)

Standard first line therapy for de novo HER2+ MBC should consist of a taxane (docetaxel or paclitaxel) in combination with pertuzumab and trastuzumab.  Patients who have received prior treatment with peruzumab and trastuzumab in either the (neo)adjuvant or metastatic setting may be considered for alternative 2^nd line therapies for disease progression within 6 months of finishing treatment.

Patients with HR+ disease should be initiated on endocrine therapy (when chemotherapy has completed) alongside maintenance anti-HER2 therapy.  Ovarian Function Suppression should be added for pre- and perimenopausal women.

Preferred regimen: Docetaxel in combination with Pertuzumab & Trastuzumab 

Alternative Regimens

• Docetaxel and Cyclophosphamide in combination with Trastuzumab
• Paclitaxel weekly in combination with Trastuzumab

SMC 928/13  Trastuzumab  is accepted for restricted use in treatment of HER2+ metastatic breast cancer

Sequential single-agent treatment is generally preferred but combination therapy should be considered if a rapid response is needed.  The optimal sequence of therapy in MBC has not been established. Available options should be discussed with the patient as part of shared decision making consultation.  The following treatments are not listed in order; restrictions to line of therapy are specified for each.

Trastuzumab deruxtecan 5.4mg/kg IV every 3 weeks until progression or toxicity

• Disease progression <6 months since (neo)adjuvant anti-HER2 treatment
• After progression on 1^st line anti-HER2 treatment for metastatic disease
• After trastuzumab emtansine

SMC 2545

Trastuzumab emtansine 3.6mg/kg IV every 3 weeks until progression or toxicity

• Disease progression <6 months since (neo)adjuvant treatment with anti-HER2 treatment
• After progression on 1^st line metastatic anti-HER2 treatment
• After trastuzumab deruxtecan

SMC 990/14

Anthracyline based treatment

Epirubicin 60mg/m²  and cyclophosphamide 600mg/m² IV  3-weekly for up to 6 cycles

Epirubicin 30mg/m² IV weekly until 12 weeks then move to 2 weekly maintenance until toxicity or disease progression.  (If proceeding with treatment beyond maximum cumulative dose of 900mg/m² the patient should be consulted and re-consented.)

Taxanes

Paclitaxel 80mg/m²  IV weekly for up to 12-18 weeks then reduce to 2 weekly until toxicity or disease progression

Docetaxel 75-80mg/m²  IV 3-weekly for up to 6 cycles

Capecitabine

Capecitabine 1000mg/m² PO bd d1-14 3-weekly. Continue until progression or toxicity

Eribulin

Eribulin 1.23mg/m²  IV on day 1 and 8 of a 21-day cycle continued until progression or toxicity

• SMC 1065/15 after at least two prior chemotherapeutic regimens for advanced disease which includes capecitabine if indicated

Tucatinib

• SMC 2398 after at least two prior anti-HER2 treatment regimens

Vinorelbine

Vinorelbine 60-80 mg/m² oral days 1+8, or 25mg/m² IV 3-weekly

Cyclophosphamide

Cyclophosphamide 50mg orally once daily continuously until progression or toxicity

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