@article{21fa7822966c403984245b95506a5378,
title = "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{\th}) 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{\th}/HER2mut, HER2 non-amplified metastatic breast cancer (MBC) in the fulvestrant-treated (n ¼ 24) or fulvestrant-na{\"i}ve 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-na{\"i}ve, 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{\th}/ HER2mut MBC. Our data support further evaluation of dual HER2 blockade for the treatment of HER2mut MBC.",
author = "Ma, {Cynthia X.} and Jingqin Luo and Freedman, {Rachel A.} and Pluard, {Timothy J.} and Nangia, {Julie R.} and Janice Lu and Frances Valdez-Albini and Melody Cobleigh and Jones, {Jason M.} and Lin, {Nancy U.} and Winer, {Eric P.} and {Kelly Marcom}, P. and Shana Thomas and Jill Anderson and Brittney Haas and Leslie Bucheit and Richard Bryce and Lalani, {Alshad S.} and Carey, {Lisa A.} and Goetz, {Matthew P.} and Feng Gao and Gretchen Kimmick and Pegram, {Mark D.} and Ellis, {Matthew J.} and Ron Bose",
note = "Funding Information: C.X. Ma reports grants from Puma Biotechnology, Department of Defense, and St. Louis Men{\textquoteright}s Group Against Cancer during the conduct of the study as well as personal fees from Seattle Genetics, AstraZeneca, Puma Biotechnology, Biovica, Athenex, OncoSignal, Eisai, Bayer, Novartis, Sanofi, Inivita, Natera, and Jacobio and grants and personal fees from Pfizer outside the submitted work. R.A. Freedman reports other support from Firefly Health outside the submitted work. T.J. Pluard reports grants and personal fees from Novartis, SeaGen, Pfizer, H3B, Gilead, AstraZeneca, Sermonix, and Daiichi; personal fees from Tempus; and grants from Zymeworks and Olema outside the submitted work. J.R. Nangia reports other support from Paxman Coolets Ltd and Novartis outside the submitted work. J. Lu reports personal fees from Pfizer, Novartis, Radius, Sanofi, and AstraZeneca during the conduct of the study. F. Valdez-Albini reports other support from Puma Biotechnology Inc. and Washington University in St. Louis during the conduct of the study. M. Cobleigh reports grants and personal fees from Seattle Genetics; personal fees from Dragonfly Therapeutics, Macrogenics, Genentech, Immunomedics, and Puma outside the submitted work; in addition, M. Cobleigh has a patent for Genomic Health with royalties paid. N.U. Lin reports grants and personal fees from AstraZeneca, SeaGen, Pfizer, and Olema Pharma; personal fees from Merck, Denali Therapeutics, Prelude Therapeutics, Affinia Therapeutics, Voyager Therapeutics, and Aleta Biopharma; and grants from Novartis, Genentech/ Roche, and Zion Pharma outside the submitted work. E.P. Winer reports personal fees from Athenex, Carrick Therapeutics, Genentech/Roche, GSK, Jounce, and Leap Therapeutics and grants from Genentech/Roche outside the submitted work. P.K. Marcom is an employee of Veracyte Inc., took position after work was completed. L. Bucheit reports other support from Guardant Health during the conduct of the study as well as other support from Guardant Health outside the submitted work. R. Bryce reports other support from Puma Biotechnology during the conduct of the study as well as other support from Puma Biotechnology outside the submitted work. A.S. Lalani reports other support from Puma Biotechnology, Inc. during the conduct of the study as well as other support from Puma Biotechnology, Inc. outside the submitted work. M.P. Goetz reports grants from Puma during the conduct of the study as well as personal fees from Research to Practice & Clinical Education Alliance; other support from AstraZeneca, Biovica, Biotheranostics, Blueprint Medicines, Eagle Pharmaceuticals, Lilly, Novartis, Pfizer, and Sermonix; and grants from Lilly, Pfizer, and Sermonix outside the submitted work. G. Kimmick reports other support from TBCRC during the conduct of the study as well as other support from Eisai, Funding Information: MutHER is an investigator-initiated trial; we thank patients and their families for participation in this study, as well as physicians, nurses, and research and regulatory coordinators for their work. We also thank PUMA Biotechnology (C.X. Ma and R. Bose), the Department of Defense (grant number BC170330, C.X. Ma and R. Bose), Siteman Cancer Center (C.X. Ma), and the St. Louis Men{\textquoteright}s Group Against Cancer (C.X. Ma) for their generous trial support. Publisher Copyright: 2022 American Association for Cancer Research",
year = "2022",
month = apr,
day = "1",
doi = "10.1158/1078-0432.CCR-21-3418",
language = "English (US)",
volume = "28",
pages = "1258--1267",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "7",
}