Triple-negative breast cancer (TNBC) refers to the absence of expression of hormone receptors and overexpression of HER2.  PD-L1 testing should be undertaken if patients are fit enough to be considered for immunotherapy.

PD-L1 Positive 

In PD-L1 positive metastatic TNBC, the preferred first line therapy is chemotherapy in combination with an immune checkpoint inhibitor.

Preferred Regimen: Paclitaxel in combination with Pembrolizumab

Paclitaxel 90mg/m² IV on days 1, 8 and 15 of a 28-day cycle in combination with Pembrolizumab 400mg IV every 6 weeks

SMC 2460  Pembrolizumab in combination with paclitaxel, for the treatment of locally recurrent unresectable or metastatic triple-negative breast cancer in adults whose tumours express PD-L1 with a CPS ≥ 10 and who have not received prior chemotherapy for metastatic disease.  Pemrolizumab is subject to a two-year clinical stopping rule.

Alternative Regimen: Nab-Paclitaxel in combination with Atezolizumab may be considered if  CPS<10, PD-L1 ≥ 1

Paclitaxel albumin (nab-paclitaxel) 100mg/m²  IV on days 1, 8 and 15 in combination with Atezolizumab 840mg IV on days 1 and 15 of a 28-day cycle

PD-L1 Negative

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.  Treatment for disease progression depends on previous therapy and HER2-Low status.

HER2-Low

HER2-low status is defined as tumours scoring 2+ or 1+ by IHC and no evidence of HER2 gene amplification. 

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

• SMC 2608 for unresectable or metastatic HER2-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing (neo)adjuvant chemotherapy.

HER2-negative

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

• SMC 2446

Treatment of unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior lines of systemic therapies, at least one of them given for unresectable locally advanced or metastatic disease.

Eribulin

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

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

Vinorelbine

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

Cyclophosphamide

Cyclophosphamide 50mg orally once daily continuous until toxicity/progression

TALAZOPARIB

Talazoparib 1mg orally once daily until disease progression/unacceptable toxicity

• SMC2607

As monotherapy for the treatment of adult patients with germline BRCA1/2 mutations, who have HER2-negative locally advanced or metastatic breast cancer. Patients should have been previously treated with an anthracycline and/or a taxane in the (neo)adjuvant, locally advanced or metastatic setting unless patients were not suitable for these treatments. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine-based therapy or considered unsuitable for endocrine-based therapy.

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