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Hurvitz Evaluates De-Escalation Strategies in Early-Stage HER2+ Breast Cancer

Caroline Seymour
Published: Wednesday, Sep 19, 2018

Sara A. Hurvitz, MD
Sara A. Hurvitz, MD
Several studies have evaluated and confirmed the benefit of de-escalating therapy for patients with early-stage HER2-positive breast cancer, but whether these therapies should replace more traditional cytotoxic regimens has yet to be determined, explained Sara A. Hurvitz, MD.

“It takes clinical judgment to determine whether to use one of these regimens or a more traditional regimen that has been evaluated in a phase III randomized trial,” said Hurvitz, an associate professor in the Department of Medicine at the University of California, Los Angeles.

Seven-year follow-up data from the APT trial, for example, suggest that patients with small HER2-positive lesions and negative lymph nodes may not require additional HER2-targeted therapy. Data from the analysis showed a 93.3% rate of disease-free survival (DFS) with the use of adjuvant paclitaxel and trastuzumab (Herceptin) for 12 weeks, followed by 39 weeks of weekly trastuzumab.

Moreover, Hurvitz noted that a short course of docetaxel and cyclophosphamide with trastuzumab is a well-tolerated regimen for lower-risk patients with HER2-positive disease.

Novel HER2-targeted therapies, such as the tyrosine kinase inhibitor (TKI) tucatinib, and more recently, the investigational antibody-drug conjugate (ADC) DS-8201a are showing potential in the paradigm.

In an interview with OncLive, Hurvitz discussed these de-escalation strategies in early-stage HER2-positive breast cancer and novel HER2-targeted therapies in development.

OncLive: Can you elaborate on de-escalation strategies that are being explored in early-stage HER2-positive breast cancer?

Hurvitz: Our approach to early-stage HER2-positive breast cancer has changed in recent years. When trastuzumab was first FDA approved for the treatment of patients with HER2-positive early-stage disease, it was primarily for patients with tumors >2 cm or those with lymph node-positive disease.

Data have come out suggesting that patients with stage I tumors—small tumors that are <1 cm in size—still have a worse 5-year DFS than those with the same size tumor who are HER2 negative. For this reason, a number of studies have begun to assess and address whether or not these tumors should be treated as higher-risk tumors with HER2-targeted approaches.

One study that looked at this was the APT trial. This was Dr Sara Tolaney's single-arm phase II study that evaluated weekly paclitaxel with weekly trastuzumab. Trastuzumab was continued for 1 full year. In this study, patients were lymph node-negative and had to have tumors that were <3 centimeters in size. The DFS was above 95% at 3 years and above 90% at 7 years.

The outcome for patients is quite good with this regimen. It wasn't a comparative study, but it does give us a good regimen to use in a patient with smaller-volume disease and has a lower risk for recurrence. Also, [it is an option] for patients who might not be able to tolerate a full chemotherapy regimen like docetaxel, carboplatin, and trastuzumab (TCH) or doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab (ACTH), elderly women, and those with comorbidities.

Another de-escalation strategy in lower-risk tumors involves 4 cycles of docetaxel and cyclophosphamide with trastuzumab, which is the other TCH regimen. This study was initiated based on Dr Stephen E. Jones’s docetaxel/cyclophosphamide (TC) regimen. The trial looked at patients who were lower risk with lymph node-negative tumors. The study showed an excellent DFS exceeding 98% in patients with stage I node-negative breast cancer. These 2 regimens are both appropriate to consider in a patient with very early-stage HER2-positive breast cancer.

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