Update on HER2-Targeted Therapy in Early Breast Cancer - Episode 7

The ExteNET Study & Management of HER2+ Breast Cancer

May 11, 2020
Sara M. Tolaney, MD, MPH

Sara M. Tolaney, MD, MPH: The ExteNET study looked at extended HER2 [human epidermal growth factor receptor 2]–directed therapy—neratinib, a pan-HER2 tyrosine kinase inhibitor—for 1 year after patients had completed their HER2-directed therapy with trastuzumab-based treatment. It’s important to realize however, that ExteNET was conducted when pertuzumab and T-DM1 [trastuzumab emtansine] were not being used in the early HER2-positive disease setting.

The trial did demonstrate that taking neratinib for 1 year after completing a year of trastuzumab did result in a reduction in disease-free survival events. There was about a 2.5% difference between the 2 arms. But what was really interesting is that this benefit seemed to be restricted to those patients who had hormone receptor–positive disease.

Where we saw that the difference between the 2 arms was about 4.4% in those patients with hormone receptor–positive disease, no difference was really seen in those patients with hormone receptor–negative tumors.

There was an interesting analysis that was done that looked at patients who had received preoperative HER2-directed therapy and had residual hormone receptor–positive HER2-positive disease. These patients had completed their year of trastuzumab and then had gone on to the ExteNET trial. There was a 7% absolute difference between those 2 arms, favoring a year of neratinib.

This suggests that in that population where we’re traditionally giving, for example, T-DM1 [trastuzumab emtansine], at this time those patients with high-risk residual disease do see an even larger benefit. The challenge is how to use these data in the current era, where we are giving pertuzumab and T-DM1 [trastuzumab emtansine] and don’t really have data on the efficacy of neratinib in this particular patient population.

In my general practice, what I say is that if a patient had a very high-risk hormone receptor–positive tumor—for example, a patient who had residual disease after preoperative therapy, and with multiple nodes involved—I do consider giving neratinib.

I acknowledge that we don’t have sufficient data to guide us and to know what the benefit is if someone had received previous pertuzumab and T-DM1 [trastuzumab emtansine]. But those patients are at high enough risk of recurrence, and extended therapy may potentially be of some benefit.

Transcript edited for clarity.