The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Trastuzumab plus endocrine therapy proved safer than trastuzumab plus chemotherapy, with similar survival outcomes, in a phase 3 trial of patients with hormone receptor-positive (HR+), HER2-positive metastatic breast cancer (mBC).

These results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting by Zhong-Yu Yuan, MD, of the Sun Yat-sen University Cancer Center in Guangzhou, China.

Dr Yuan noted that anti-HER2 therapy plus chemotherapy has shown survival benefits in patients with HER2-positive mBC. However, endocrine-based therapy is preferred over chemotherapy in patients with HR+ mBC because endocrine therapy is safer. There is no evidence to support a preferred regimen in patients with HR+, HER2-positive mBC.

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With this in mind, Dr Yuan and colleagues conducted a phase 3, randomized trial ( identifier: NCT01950182) comparing the regimens in 392 adults with HR+, HER2-positive advanced breast cancer. The patients had to have a disease-free interval longer than 12 months. The disease-free interval was defined as the time from diagnosis to first recurrence after (neo)adjuvant therapy.

Patients were randomly assigned to trastuzumab plus endocrine therapy (estrogen receptor modulators or aromatase inhibitors; n = 196) or trastuzumab plus chemotherapy (taxanes, capecitabine, or vinorelbine; n = 196).

At baseline, the patients’ median age was 49 years in the endocrine therapy arm and 50 years in the chemotherapy arm. About 30% of patients were premenopausal, about 60% had visceral involvement, and about 71% had fewer than 2 sites of metastasis.

Overall, there was no significant difference between the treatment arms in progression-free survival (PFS). The hazard ratio (HR) was 0.88 (95% CI, 0.71-1.09; P =.250).

There were no significant between-arm differences in PFS for most subgroups. However, PFS favored the chemotherapy arm (HR, 1.39) in patients with a disease-free interval of 24 months or less and favored the endocrine therapy arm (HR, 0.77) in patients with a disease-free interval longer than 24 months (P =.016).

There was no significant difference between the treatment arms in overall survival (HR, 0.82; 95% CI, 0.65-1.04; P =.090).

Dr Yuan noted that adverse events were significantly lower in the endocrine therapy arm. For example, the grade 1/2 nausea rates were 12.2% in the endocrine therapy arm and 44.9% in the chemotherapy arm.

Grade 3 leukopenia occurred at a rate of 0.5% in the endocrine therapy arm and 15.8% in the chemotherapy arm (grade 4, 0% and 5.1%, respectively). Grade 1/2 alopecia rates were 4.1% and 45.4%, respectively.

“Endocrine therapy plus anti-HER2 therapy was noninferior to and had fewer toxicities compared with chemotherapy,” Dr Yuan concluded. “Exploratory analyses revealed that trastuzumab plus endocrine therapy was likely to be more beneficial in patients with a DFI [disease-free interval] more than 24 months, while trastuzumab plus chemotherapy was preferred in patients with a DFI of fewer than 24 months.”

Disclosures: This research was supported by Sun Yat-sen University. The authors reported having no conflicts of interest.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


Yuan Z, Huang J-J, Hua X, et al. Trastuzumab plus endocrine therapy or chemotherapy as first-line treatment for metastatic breast cancer with hormone receptor-positive and HER2-positive: the sysucc-002 randomized clinical trial. J Clin Oncol. 2021;39:(suppl 15; abstr 1003). doi:10.1200/JCO.2021.39.15_suppl.1003