Breast Cancer Coverage from Every Angle

AACR 2021: Neratinib Plus Fulvestrant for HER2-Mutant Metastatic Breast Cancer

By: Vanessa A. Carter, BS
Posted: Thursday, April 15, 2021

Cynthia X. Ma, MD, PhD, of Washington University, St. Louis, Missouri, and colleagues conducted a study to identify whether neratinib plus fulvestrant would improve outcomes in HER2-mutant metastatic breast cancer and whether adding trastuzumab at disease progression could reduce treatment resistance. They discovered that neratinib, with or without fulvestrant, demonstrated activity, and the addition of trastuzumab induced further response. Their results were presented at the American Association for Cancer Research (AACR) Annual Meeting 2021 (Abstract CT026).

The researchers enrolled 40 patients with estrogen receptor (ER)-positive or -negative, HER2-mutant metastatic breast cancer. Individuals who were ER-positive were divided into two cohorts (naive or fulvestrant-treated) and received neratinib plus fulvestrant with diarrhea prophylaxis; ER-negative patients were administered neratinib alone. When participants reached progressive disease, trastuzumab was added to the regimen.

Of the 35 patients evaluable for response, 21 were previously treated with fulvestrant, 10 were fulvestrant-naive, and 4 were ER-negative. All but one patient discontinued treatment due to progressive disease. The median age was 63 years, with 3 patients having received previous therapy; 13 had lobular breast cancer, and 32 had visceral metastases. Of ER-positive patients, 68% previously used a CDK4/6 inhibitor.

A total of 1 fulvestrant-treated patient achieved a complete response, 4 had a partial response, and 13 reached stable disease. Their median progression-free survival was 24 weeks, and the clinical benefit rate was 40%. Of fulvestrant-naive participants, partial response and stable disease were achieved by three patients each. A partial response was reached by one patient who was ER-negative. When trastuzumab was added at progressive disease, it induced clinical benefit in four patients, with a progression-free survival of 28 weeks.

The most common adverse events were grade 3 diarrhea (21%) and grade 3 fatigue (5%). No grade 4 or higher adverse events were observed.

Disclosure: For full disclosures of the study authors, visit

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.