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

Abstract

PURPOSE:

HER2 mutations (HER2mut) induce endocrine resistance in estrogen receptor-positive (ER+) 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 ER+/HER2mut, HER2 non-amplified metastatic breast cancer (MBC) in the fulvestrant-treated (n = 24) or fulvestrant-naïve cohort (n = 11). Patients with ER-negative (ER-)/HER2mut MBC received neratinib monotherapy in an exploratory ER- cohort (n = 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 ER+/HER2mut MBC. Our data support further evaluation of dual HER2 blockade for the treatment of HER2mut MBC.

• Authors: 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 Goetz, Feng Gao, Gretchen Kimmick, Mark D Pegram, Matthew J Ellis, Ron Bose
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 28 Issue 7 Pg. 1258-1267 (04 01 2022) ISSN: 1557-3265 [Electronic] United States
• PMID: 35046057 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't)
• Copyright: ©2022 American Association for Cancer Research.

Chemical References

• Quinolines
• Fulvestrant
• Receptor, ErbB-2
• neratinib

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Breast Neoplasms (drug therapy, genetics, pathology)
• Female
• Fulvestrant
• Humans
• Quinolines
• Receptor, ErbB-2 (genetics, therapeutic use)