It’s been nearly a decade since the U.S. Food and Drug Administration approved trastuzumab for the adjuvant treatment of women with node-positive, human epidermal growth factor receptor type 2 (HER2)-overexpressing breast cancer, as part of a regimen comprising doxorubicin, cyclophosphamide, and paclitaxel (ACTH).1

What remains unclear is exactly which women with early-stage disease might benefit most from treatment, and there is no standard treatment approach.

Four phase 3 randomized trials in 8,000-plus patients found risk of recurrence decreased by about half and overall survival improved when trastuzumab was administered with or after chemotherapy, Sara M. Tolaney, MD, MPH, of Dana-Farber Cancer Institute in Boston, MA, and colleagues wrote in a recent article in the New England Journal of Medicine‘s.

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However, these studies focused primarily on women with stage 2 or 3 HER2-positive disease, primarily because those with small, node-negative HER2-positive breast cancers were ineligible for the pivotal trials of adjuvant trastuzumab.2

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Now, results from the uncontrolled Adjuvant Paclitaxel and Trastuzumab (APT) study of 406 women with HER2-positive, node-negative tumors 3 cm or larger “really demonstrate that lower-intensity chemotherapy and trastuzumab is associated with fewer side effects,” with a low event rate that is “reasonable and appealing,” Dr. Tolaney told Cancer Therapy Advisor, calling this regimen a “new standard of care for stage 1 HER2-positive disease.”

Patients received postoperative weekly treatment with paclitaxel and trastuzumab for 12 weeks, followed by 9 months of treatment with trastuzumab alone. The primary end point was invasive disease-free survival.

At a median follow-up of 4 years, the 3-year event rate was 98.7%. Twelve patients relapsed, 2 due to distant metastatic breast cancer.

Two patients had symptomatic congestive heart failure that normalized after trastuzumab was discontinued, and, of 13 patients with significant asymptomatic declines in ejection fraction, 11 resumed treatment with trastuzumab after a brief interruption.