Metastatic HER2-Negative Breast Cancer – Chemo- and Targeted Therapy
Introduction
Introduction
- 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.
Treatment
Treatment
New Recommendation from 2023 Guideline Rapid Recommendation Update
New Recommendation from 2022 Guideline Rapid Recommendation Update
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.
( EB , M, B , S )Practical Information: Patients may be offered either platinum- or non-platinum-based regimens based on individualized patient and provider assessment of preferences, risks, and benefits.
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.
( EB , M, B , S )Practical Information: Small single-arm studies show that oral PARP inhibitor therapy demonstrates high response rates in metastatic breast cancer encoding DNA repair defects, such as germline PALB2 mutation carriers and somatic BRCA mutations. It should also be noted that the randomized PARP inhibitor trials made no direct comparison with taxanes, anthracyclines, or platinums. Comparative efficacy against these compounds is unknown.
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.
( EB , M, B , S )Practical Information: Treatment choice should be based on individualized patient and provider assessment of preferences, risks, and benefits.
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.
( EB , M, B , S )Practical Information: Small single-arm studies show that oral PARP inhibitor therapy demonstrates high response rates in metastatic breast cancer encoding DNA repair defects, such as germline PALB2 mutation carriers and somatic BRCA mutations. It should also be noted that the randomized PARP inhibitor trials made no direct comparison with taxanes, anthracyclines, or platinums. Comparative efficacy against these compounds is unknown.
Table 1. Targeted Therapies for Metastatic (or locally advanced) Breast Cancer
| Company Product Generic Name | Type | Indications | Dose |
|---|---|---|---|
| pembrolizumab | Immune Checkpoint Inhibitor | Triple-negative breast cancer expressing PD-L1 | 200 mg every 3 weeks or 400 mg every 6 weeks with chemotherapy |
| sacituzumab govitecan | 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 |
| olaparib | PARP Inhibitor | 2nd line for HER2-negative metastatic breast cancer | 300 mg taken orally twice daily |
| talazoparib | PARP Inhibitor | Deleterious or suspected deleterious germline BRCA-mutated ( gBRCAm) HER2-negative breast cancer | 1 mg taken orally once daily |
| eribulin mesylate | 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 |
| ixabepilone | 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 |
Figure 1. Management of Metastatic HR-positive Breast Cancer
Figure 2. Management of Metastatic Triple Negative Breast Cancer
Recommendation Grading
Abbreviations
- BRCA: BReast CAncer Gene
- BRCA1: BReast CAncer Gene 1
- BRCA2: BReast CAncer Gene 2
- HER2: Human Epidermal Growth Factor Receptor 2
- HR: Hormone Receptor
- OS: Overall Survival
- PARP: Poly (ADP -ribose) Polymerase
Source Citation
Moy B, Rumble RB, Come S et al. Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor–Negative: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2023 January 10. doi: 10.1200/JCO.22.02807
Moy B, Rumble RB, Come S et al. Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor–Negative: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2022 August 4. doi: 10.1200/JCO.22.01533
Moy B, Rumble RB, Come S et al. Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor–Negative: ASCO Guideline Update. J Clin Oncol. 2021;39(35):3938-3958. doi:10.1200/jco.21.01374.