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Optimizing HER2-Targeted Therapy

Gina Battaglia, PhD
Published: Monday, Mar 19, 2018

Sara A. Hurvitz, MD
Sara A. Hurvitz, MD
The introduction of HER2-targeted therapies has drastically improved long-term survival for patients with HER2-positive breast cancer and provided numerous treatment options for all stages of the disease. “The good side to HER2-positive disease is the number of therapies we have available,” Sara Hurvitz, MD, director of the Breast Cancer Clinical Research Program at the University of California, Los Angeles (UCLA), and associate professor at the David Geffen School of Medicine at UCLA said in an interview with OncLive. “Women can live a long time with this disease.”

Choosing which patients benefit from treatment beyond the standard first-line regimen and where new HER2-targeted agents and therapeutic approaches fit into treatment algorithms will be the next steps moving forward, according to Hurvitz and Sunil Verma, MD, professor and head of the Department of Oncology at the University of Calgary, who also shared his insight in an interview with OncLive.

To Escalate or De-escalate Therapy?

Although targeted therapies are a mainstay of treatment, results from recent research show that management of HER2-positive breast cancer should not be a one-size-fits-all approach (Table). Identifying the low-risk patients who can receive standard-of-care treatment and the high-risk patients who should receive additional therapy is important to individualizing treatment and were the the central theme of Verma's talk, “Individualizing Therapy for Early-Stage HER2+ Breast Cancer: To Escalate or De-escalate?" at the recent Miami Breast Cancer Conference® (MBCC).


TABLE. Novel Agents Explored for Potential in Individualized HER2-Targeted Therapy

A 7-year follow-up analysis of data from the APT trial1 showed that adjuvant paclitaxel (Taxol) plus trastuzumab (Herceptin) for 12 weeks, followed by weekly trastuzumab for 39 weeks, led to a disease-free survival (DFS) rate of 93.3% and incidences of distant and local/regional recurrences of 1.0% and 1.2%, respectively, among patients with small HER2-positive lesions and negative lymph nodes. Because the standard approach of taxane-based chemotherapy plus trastuzumab “appears to be very effective,” Verma said, additional HER2-targeted therapy is likely unnecessary for low-risk patients.

Data from the APHINITY trial2 suggest that the standard approach may also be adequate for patients with high-risk node-negative disease. Although the addition of pertuzumab (Perjeta) to standard adjuvant chemotherapy plus 1 year of trastuzumab significantly improved 3-year invasive DFS in patients with node-positive or highrisk node-negative disease (94.1% vs 93.2% with placebo), the improvement was driven primarily by the node-positive subgroup, as the invasive DFS was not different between pertuzumab and placebo in patients with node-negative disease (97.5% vs 98.4% with placebo).

However, Verma noted that patients at higher risk for recurrence or metastases, such as those with node-positive disease or significant residual disease after neoadjuvant therapy, may benefit from treatment beyond the standard chemotherapy and trastuzumab. Although the improvement was modest in the overall intent-to-treat population, the 3-year rate of invasive DFS was significantly improved with pertuzumab in the node-positive subgroup (92.0% vs 90.2% in the placebo group) and was sufficient for FDA approval for pertuzumab in the adjuvant setting in December 2017.

Extended treatment with neratinib (Nerlynx) may also benefit high-risk patients, although Verma said that the benefits appear to be restricted to patients with HER2-positive and hormone receptor (HR)-positive disease. An exploratory subgroup analysis from the phase III ExteNET trial3 showed that neratinib lowered the risk of recurrence by 51% in HR-positive patients versus 7% in HR-negative patients.

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