Metastatic HER2-Negative Breast Cancer – Chemo- and Targeted Therapy
- The purpose of this guideline update is to gather and examine the evidence published since the 2014 guidelinea and offer a series of updated recommendations for advanced HER2-negative breast cancer, if warranted.
- Note that while this guideline provides recommendations for chemo- and targeted therapy for patients with HER2-negative metastatic breast cancer that is either endocrine-pretreated or hormone receptor-negative, a companion guidelineb provides endocrine therapy and targeted therapy recommendations, including CDK 4/6 and PI3 kinase inhibition, for hormone receptor-positive metastatic breast cancer patients.
- Patients with metastatic triple negative breast cancer with expression of programmed cell death ligand-1 (PD-L1-positive) and no existing contraindications may be offered the addition of immune checkpoint inhibitor to chemotherapy (atezolizumab plus nab-paclitaxel or pembrolizumab plus chemotherapy) as first-line therapy.
- Patients with metastatic triple negative breast cancer without expression of programmed cell death ligand-1 (PD-L1-negative) should be offered single agent chemotherapy rather than combination chemotherapy as first-line treatment, although combination regimens may be offered for symptomatic or immediately life-threatening disease for which time may allow only one potential chance for therapy.
- Patients with metastatic triple negative breast cancer who have received at least two prior therapies for metastatic disease should be offered treatment with sacituzumab govitecan.
- Patients with metastatic triple negative breast cancer with germline BRCA1 or 2 mutations who have previously been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic disease setting may be offered an oral PARP inhibitor (olaparib or talazoparib) rather than chemotherapy.
- Patients with metastatic hormone receptor-positive (HR-positive) breast cancer with disease progression on a prior endocrine agent with or without targeted therapy may be offered treatment with either endocrine therapy with or without targeted therapy (refer to the companion ASCO guideline on Endocrine Therapy and Targeted Therapy for Hormone Receptor-Positive, HER2-negative Metastatic Breast Cancer [Burstein et al. J Clin Oncol. doi: 10.1200/JCO.21.01392] for details) or single-agent chemotherapy.
- Patients with metastatic HR-positive but HER2-negative breast cancer with germline BRCA1 or 2 mutations who are no longer benefiting from endocrine therapy may be offered an oral PARP inhibitor in the first- through to third-line setting rather than chemotherapy.
- Patients with HR-positive HER2-negative metastatic breast cancer no longer benefiting from endocrine therapy should be offered single agent chemotherapy rather than combination therapy, although combination regimens may be offered for symptomatic or immediately life-threatening disease for which time may allow only one potential chance for therapy.
- No recommendation regarding at which point a patient’s care should be transitioned to hospice or best supportive care only is possible at this time.
Table 1. Targeted Therapies for Metastatic (or locally advanced) Breast Cancer
|Immune Checkpoint Inhibitor||Triple-negative breast cancer expressing PD-L1||200 mg every 3 weeks or 400 mg every 6 weeks with chemotherapy|
|Trop-2-directed antibody and topoisomerase inhibitor conjugate||3rd line for triple-negative breast cancer||10 mg/kg IV once weekly on Days 1 and 8 of continuous 21-day treatment|
|AstraZeneca / Merck
|PARP Inhibitor||2nd line for HER2-negative metastatic breast cancer||300 mg taken orally twice daily|
|PARP Inhibitor||Deleterious or suspected deleterious germline BRCA-mutated ( gBRCAm) HER2-negative breast cancer||1 mg taken orally once daily|
|Microtubule inhibitor for single agent chemotherapy||3rd line for metastatic breast cancer||1.4 mg/m2 IV over 2–5 minutes on Days 1 and 8 of a 21 day cycle|
|Microtubule inhibitor for single agent chemotherapy or with capecitabine||2nd line for the treatment of metastatic or locally advanced breast cancer||40 mg/m2 IV over 3 hours every 3 weeks|