Fast Five Quiz: HER2+ Metastatic Breast Cancer Management

Winston Tan, MD


January 10, 2022

In the metastatic setting, a pivotal phase 3 trial compared first-line chemotherapy plus trastuzumab vs chemotherapy alone in HER2+ patients. Trastuzumab plus chemotherapy was associated with a significant improvement in time to disease progression (7.4 months vs 4.6 months), objective response rate (50% vs 32%), and 1-year survival (25.1 months vs 20.3 months) compared with chemotherapy alone. Additionally, evidence suggested that in women with advanced HER2+ breast cancer, survival is better with up-front use of trastuzumab plus chemotherapy than it is with sequential administration.

Results from the CLEOPATRA trial established the combination of pertuzumab, trastuzumab, and a taxane as the standard of care for first-line therapy of HER2+ metastatic breast cancer. In CLEOPATRA, the addition of pertuzumab to trastuzumab and docetaxel resulted in a median progression-free survival (PFS) of 18.5 months — 6.1 months longer than with trastuzumab and docetaxel — with minimal to no increase in cardiac toxic effects.

End-of-study analysis of CLEOPATRA demonstrated that improvements in overall survival with pertuzumab, trastuzumab, and docetaxel were maintained after a median of more than 8 years of follow-up, during which time long-term safety and cardiac safety profiles were also maintained.

In the phase 3 EMILIA trial, HER2+ advanced breast cancer patients previously treated with trastuzumab and taxane were randomly assigned to treatment with the antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) or lapatinib plus capecitabine. T-DM1 was shown to significantly prolong PFS (9.6 months vs 6.4 months) and overall survival (30.9 months vs 25.1 months) compared with lapatinib plus capecitabine, and was associated with a better toxicity profile.

Tucatinib is an orally bioavailable, small molecule tyrosine kinase inhibitor that is highly selective for HER2. It is indicated in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2–based regimens in the metastatic setting.

According to the HER2CLIMB trial, in which heavily pretreated patients were separated to receive trastuzumab and capecitabine plus either tucatinib or placebo, the median PFS in the tucatinib-treated group was 7.8 months compared with 5.6 months in the control arm. The median overall survival in the tucatinib-treated arm was 21.9 months vs 17.4 months in the control arm. The median PFS for patients with baseline brain metastases in the tucatinib-treated arm was 7.6 months compared with 5.4 months for patients in the control arm.

Lapatinib, a tyrosine kinase inhibitor, is indicated for the treatment of metastatic breast cancer in HER2+ patients after progression on trastuzumab. It is known to block multiple epidermal growth factor receptors and is generally well tolerated; its main toxicities are diarrhea, skin rash, fatigue, and nausea. Cardiac toxicity associated with lapatinib is infrequent.

For additional information, refer to the NCCN Breast Cancer Clinical Practice Guidelines, 2018 ASCO Guidelines, and the 5th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer.

Learn more about the systemic treatment of HER2+ advanced metastatic breast cancer.


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