Background of De-Escalation Approach to HER2+ Breast Cancer Treatment

Neil Vasan, MD, PhD, assistant professor of medicine at Herbert Irving Comprehensive Cancer Center, Columbia University, discusses how past studies have supported de-escalated approaches and other improvements to treatment for patients with HER2-positive breast cancer.

Vasan says that previous approaches included multiple chemotherapies given along with HER2-targeted agents such as pertuzumab (Perjeta) as well as dual HER2 therapies.

Trials were then initiated to investigate a de-escalated approach focusing on patients with T1 tumors of 2 cm or less. The phase 2 APT trial (NCT00542451) enrolled patients with node-negative HER2-positive breast cancer who had tumors of 3 cm or less, the vast majority of whom had T1 tumors. Patients received adjuvant paclitaxel and trastuzumab (Herceptin). The trial resulted in 93% rate of 7-year disease-free survival (DFS) while offering less toxicity than more aggressive treatment.

Vasan adds that further improvements are being made to improve outcomes of early treatment, including the antibody-drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1; Kadcyla) being used to reduce the risk of recurrence when offered in the adjuvant setting in the KATHERINE trial (NCT01772472), and the use of therapies that can reduce residual disease for patients who previously received neoadjuvant chemotherapy before resection.

TRANSCRIPTION:

0:08 | There used to be a one-size-fits-all type of treatment approach for these tumors, which used to be polychemotherapy—multiple chemotherapy agents—with anti-HER2 therapies. And certainly, with the development of pertuzumab in the metastatic setting, that made its way into the curable setting, as well. So anti-HER2 therapy was often what we call dual anti-HER2 therapy, 2 agents.

But de-escalation trials were run several years ago, especially looking at these patients with smaller tumors, T1 tumors, tumors that are 2 cm or less. This trial did include a couple, about 10% of patients with tumors larger than 2 cm, but most of the patients [had tumors] less than 2 cm and [were] lymph-node negative.

0:53 | They found—this was a single-arm study; this is what is called the APT trial, which was published in [the New England Journal of Medicine], and this trial was a single-arm phase 2 trial—that patients who received just 1 chemotherapy agent, paclitaxel, and 1 anti-HER2 therapy, trastuzumab, had excellent DFS rates that persisted even at the 7-year follow-up. This is fantastic news for our patients because this means that we can give less therapy, less chemotherapy, less anti-HER2 therapy, and not surprisingly there are fewer [adverse events], and patients can still have excellent outcomes and excellent chances of cure.

Certainly in this HER2 space, we are now starting to see other drugs like T-DM1….This is an ADC that is approved in the metastatic setting that has [also] been tested in clinical trials in the adjuvant setting. We also have drugs that we can offer to patients who have residual disease after having received neoadjuvant therapy; [these patients received] chemotherapy initially to downstage the tumor and then [underwent] surgery.

Making sense of all these therapeutic options is something that oncologists have to do every day for our patients. But it’s very motivating because we are trying to tailor treatment as best as possible.