The Phase II MutHER Study of Neratinib Alone and in Combination with Fulvestrant in HER2-Mutated, Non-amplified Metastatic Breast Cancer

Cynthia X. Ma, Jingqin Luo, Rachel A. Freedman, Timothy J. Pluard, Julie R. Nangia, Janice Lu, Frances Valdez-Albini, Melody Cobleigh, Jason M. Jones, Nancy U. Lin, Eric P. Winer, P. Kelly Marcom, Shana Thomas, Jill Anderson, Brittney Haas, Leslie Bucheit, Richard Bryce, Alshad S. Lalani, Lisa A. Carey, Matthew P. GoetzFeng Gao, Gretchen Kimmick, Mark D. Pegram, Matthew J. Ellis, Ron Bose

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Purpose: HER2 mutations (HER2mut) induce endocrine resistance in estrogen receptor–positive (ERþ) breast cancer. Patients and Methods: In this single-arm multi-cohort phase II trial, we evaluated the efficacy of neratinib plus fulvestrant in patients with ERþ/HER2mut, HER2 non-amplified metastatic breast cancer (MBC) in the fulvestrant-treated (n ¼ 24) or fulvestrant-naïve cohort (n ¼ 11). Patients with ER-negative (ER)/HER2mut MBC received neratinib monotherapy in an exploratory ER cohort (n ¼ 5). Results: The clinical benefit rate [CBR (95% confidence interval)] was 38% (18%–62%), 30% (7%–65%), and 25% (1%–81%) in the fulvestrant-treated, fulvestrant-naïve, and ER cohorts, respectively. Adding trastuzumab at progression in 5 patients resulted in three partial responses and one stable disease ≥24 weeks. CBR appeared positively associated with lobular histology and negatively associated with HER2 L755 alterations. Acquired HER2mut were detected in 5 of 23 patients at progression. Conclusions: Neratinib and fulvestrant are active for ERþ/ HER2mut MBC. Our data support further evaluation of dual HER2 blockade for the treatment of HER2mut MBC.

Original languageEnglish
Pages (from-to)1258-1267
Number of pages10
JournalClinical Cancer Research
Volume28
Issue number7
DOIs
StatePublished - Apr 1 2022

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