Lisa Carey, MD, on Therapy for Early-Stage HER2+ Breast Cancer

In Clinical Studies News by Barbara Jacoby

By: Jeff Minerd


Many patients overtreated, may benefit from de-escalation

Advances in research and clinical practice have transformed HER2+ breast cancer from a disease with a poor prognosis to one with among the “best,” with relatively low relapse rates and deaths. However, as more complex and lengthy therapies have been developed to maximize outcomes, many patients are being overtreated, according to Lisa Carey, MD, deputy director of clinical sciences at the University of North Carolina at Chapel Hill, and colleagues, writing in the 2020 ASCO Educational Book.

Furthermore, Carey’s group said, anti-HER2 regimens are among the most expensive, “warranting the current focus on efforts to rationally direct intensified treatment of those who need it and de-intensified treatments for those who are likely to do well with less.”

In the following brief interview, Carey discussed strategies for escalating and de-escalating therapy for patients with early-stage HER2+ breast cancer.

With current treatment paradigms, many patients with early-stage HER2+ breast cancer are being over-treated. Why is that?

Carey: Because outside of very small node-negative cancer, we do not know how we can get no or less chemotherapy, or no or less anti-HER2 therapy, so we end up giving a year or more of treatment to a high proportion of patients.

What can you tell us about identifying patients who would benefit from treatment de-escalation?

Carey: Observational studies suggest excellent outcomes for patients with T1aN0, who can reasonably omit anti-HER2 and chemotherapy. From APT and ATEMPT, we know that larger T1N0 tumors can be treated with paclitaxel + trastuzumab alone — or T-DM1 (ado-trastuzumab emtansine; Kadcyla) if available. For the rest, we need to leverage better understanding of the prognostic implications of biologic elements such as immune activation, tumor subtype, etc.

What about patients who would benefit from escalated therapy?

Carey: The best escalation we have is the use of pCR [pathologic complete response] versus residual disease to identify those who would benefit from changing to T-DM1 rather than completing a trastuzumab-based adjuvant regimen after neoadjuvant chemotherapy + anti-HER2. Trials in development, such as A011801 from the Alliance, will look at the addition of tucatinib (Tukysa) to TDM1 in the high-risk residual disease setting.

Do you have any advice on discussing these options with patients?

Carey: These are all evidence-based options — frankly that is how I frame the conversation with patients.

Read the paper here and expert commentary about the clinical implications here.