Citations 1
The Phase II MutHER Study of Neratinib Alone and in Combination with Fulvestrant in HER2-Mutated, Non-amplified Metastatic Breast Cancer
Ma, Cynthia X., Luo, Jingqin , Freedman, Rachel A., Pluard, Timothy , Nangia, Julie R., Lu, Janice, Valdez-Albini, Frances, Cobleigh, Melody, Jones, Jason M., Lin, Nancy U. , Thomas, Shana, Anderson, Jill, Haas, Brittney, Bucheit, Leslie, Bryce, Richard , Lalani, Alshad S., Gao, Feng, Kimmick, Gretchen, Pegram, Mark D. , Bose, Ron , Cobleigh, Melody , Kimmick, Gretchen , Pluard, Timothy J , Winer, Eric , Marcom, Paul Kelly , Bryce, Richard , Carey, Lisa A , Goetz, Matthew P , Pegram, Mark D , Ellis, Matthew J , Bose, Ron , Lin, Nancy U , Luo, Jingqin , Ma, Cynthia X., Freedman, Rachel A., Nangia, Julie R., Lu, Janice, Valdez-Albini, Frances, Jones, Jason M., Thomas, Shana, Anderson, Jill, Haas, Brittney, Bucheit, Leslie, Lalani, Alshad S., Gao, Feng
Clinical Cancer Research | January 19, 2022 | Volume: 28 | Issue: 7 | Pages: 1258-1267
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.