For women with human epidermal growth factor receptor type 2 (HER2)-positive early breast cancer, delaying trastuzumab until chemotherapy is completed may impair outcomes, according to findings from the landmark N9831 trial. The findings were presented by Edith Perez, MD, director of the Breast Cancer Program at the Mayo Clinic, Jacksonville, Florida.
The addition of 52 weeks of trastuzumab, either after standard chemotherapy with doxorubicin/cyclophosphamide followed by paclitaxel (AC-T) or concurrently with the paclitaxel, reduced the risk of breast cancer recurrence by 33% overall, but the benefit was significantly greater when trastuzumab was given concurrently with the paclitaxel portion of the chemotherapy, an approach that can now be recommended, Perez said.
"Often, the research community conducts studies that conclude with 'that was interesting, but let's do more research,'" she noted. "This is an important finding on how we can help prevent breast cancer recurrence and improve survival...This will clearly inform physician decision-making."
The N9831 trial, by the North Central Cooperative Trials Group, consisted of two comparisons. The first comparison included 2448 women randomized to chemotherapy alone or chemotherapy followed by trastuzumab. The proportion of women remaining diseasefree increased from 72% with chemotherapy alone to 80% with the addition of trastuzumab. The second comparison, which included 1903 women who were analyzed according to whether they received trastuzumab after chemo therapy (sequentially) or along with chemo therapy (concurrently with paclitaxel), continued for 52 weeks.
The sequential use of trastuzumab reduced recurrences by 33% over chemotherapy alone. At a median follow-up time of 5.3 years, 80% of women receiving 52 weeks of trastuzumab after chemotherapy were alive and disease-free, compared with 72% not receiving trastuzumab. But by giving trastuzumab concurrently with the paclitaxel portion of chemotherapy, the risk of recurrence was reduced by an additional 25%, compared with the sequential delivery of the drug. With concurrent trastuzumab, 84% of women were alive and disease-free compared with 80% of women treated sequentially, Perez reported.
"Based on a positive risk-benefit ratio, we recommend that adjuvant tras tuzumab be incorporated in a concurrent fashion with taxane chemotherapy," she said.