Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Publication Date: May 30, 2022
Last Updated: May 31, 2022

Treatment

HER2+

First-Line

Recommendation 1.0
Clinicians should recommend HER2-targeted therapy-based combinations for first-line treatment, except for highly selected patients with estrogen receptor-positive (ER+) or progesterone receptor-positive (PgR+) and HER2-positive disease for whom clinicians may use endocrine therapy alone. (EB, , H, S)
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Recommendation 1.1
Clinicians should recommend the combination of trastuzumab, pertuzumab, and a taxane for first-line treatment, unless the patient has a contraindication to taxanes. (EB, B, H, S)
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Second-Line

Recommendation 2.0
If a patient’s HER2-positive advanced breast cancer has progressed during or after first-line HER2-targeted therapy, clinicians should recommend second-line HER2-targeted therapy-based treatment. (EB, , H, S)
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Recommendation 2.1 (updated)
If a patient’s HER2-positive advanced breast cancer has progressed during or after first-line HER2-targeted therapy (and the patient has not received trastuzumab deruxtecan), clinicians should recommend trastuzumab deruxtecan as a second-line treatment. (EB, B, M, S)
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Third-Line

Recommendation 3.0
If a patient’s HER2-positive advanced breast cancer has progressed during or after second-line or greater HER2-targeted treatment, clinicians should recommend third-line or greater-line HER2-targeted therapy-based treatment. (EB, , I, M)
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Overall, there are a lack of head-to-head trials, therefore there is insufficient evidence to recommend one regimen over another. The patient and clinician should discuss differences in treatment schedules, routes, and toxicities during the decision-making process.

Options include the following:
Recommendation 3.1 (updated)
If a patient’s HER2-positive advanced breast cancer has progressed during or after second-line or greater HER2-targeted treatment and the patient has already received pertuzumab and trastuzumab deruxtecan, clinicians should recommend third-line or greater HER2-targeted therapy-based treatment. (, , , )
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Recommendation 3.1.1 (updated)
If a patient has not received trastuzumab emtansine (T-DM1) in second-line, should offer T-DM1 regimen. (EB, B, H, S)
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Recommendation 3.1.2 (updated)
May offer tucatinib combined with trastuzumab and capecitabine. (EB, B, M, S)
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Recommendation 3.1.3 (updated)
May offer trastuzumab deruxtecan. (EB, B, M, S)
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Recommendation 3.1.4 (updated)
May offer neratinib combined with capecitabine. (EB, B, M, W)
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Recommendation 3.1.5
May offer lapatinib and trastuzumab. (EB, B, M, W)
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Recommendation 3.1.6
May offer lapatinib and capecitabine. (EB, B, M, W)
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Recommendation 3.1.7
May offer other combinations of chemotherapy and trastuzumab. (EB, B, M, W)
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Recommendation 3.1.8 (updated)
May offer margetuximab plus chemotherapy. (EB, B, M, W)
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Recommendation 3.1.9
If a patient has not received pertuzumab, clinicians may offer pertuzumab. (IC, B, Ins, W)
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Recommendation 3.2.0
May offer hormonal therapy (in patients with ER+ and/or PgR+ disease). (EB, B, M, W)
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Recommendation 3.2.1 (updated)
May offer abemaciclib combined with trastuzumab and fulvestrant. (EB, B, M, W)
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Overview

Title

Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Authoring Organization

American Society of Clinical Oncology