Abstract OT-28-05: Solti-1718 NEREA trial: Neratinib in hormone receptor (HR)-positive/HER2-negative HER2-Enriched (HER2-E) advanced breast cancer (BC)

Background: HR+/HER2-negative BC represent ∼70% of all newly diagnosed breast tumors. BC is a clinically and biologically heterogenous disease where intrinsic subtypes play a role(1-3). Non-luminal subtypes within HR+/HER2-negative disease do not benefit at the same extent from standard of care treatments as the luminal subtypes(1). Thus, other strategies are needed. HER2-E subtype represents approximately 6.6-11.0% of HR+/HER2-negative tumors and is enriched in twice as many cases in metastatic tumors. According to EGF30008 trial, HER2-E advance BC patients despite presenting poor outcomes across treatments, showed more benefit from anti-HER2 therapy. SOLTI-1718 NEREA aims to evaluate whether EGFR/ERBB2 axis inhibition by neratinib improves efficacy in terms of progression-free survival (PFS) in patients with advanced HR+/HER2-negative disease resistant to an endocrine treatment (ET). Methods: SOLTI-1718 NEREA is an open-label, single arm, multicenter and multinational phase II clinical trial following a Simon’s 2-stage design with one interim and one final efficacy analysis. Locally advanced or metastatic HER2-E, HR+/HER2-negative BC patients who had recurrence or progression while receiving previous ET will be included. Treatment schedule will consist on neratinib 240 mg daily in combination with ET, with either exemestane, fulvestrant or tamoxifen. All patients will take prophylactic loperamide with an established dosing scheme during the first cycle and on demand in subsequent cycles. Tumor assessments will be performed at baseline and every 8 weeks during the first year, and every 12 weeks thereafter. Interim analysis will be performed after 33 patients are evaluable. If 15 to 27 patients achieved a PFS at 6 months (PFS6), the trial will continue to second stage, otherwise it will be stopped for futility ( Citation Format: Cristina Saura, Eva Ciruelos, Maria Vidal, Laia Garrigos, Mireia Margeli, Serafin Morales, Xavier Gonzalez-Farre, Javier Salvador Bofill, Isabel Blancas, Joan M Gasent, Elena Lopez-Miranda, Ana Godoy, Maria Iglesias, Pedro Sanchez-Rovira, Fernando Hernao, Isabel Gallegos, Catarina Pulido, Sara Alves, Diogo Branco, Jose Passos-Coelho, Santiago Escriva-de-Romani, Juan M Ferrero-Cafiero, Patricia Villagrasa, Aleix Prat. Solti-1718 NEREA trial: Neratinib in hormone receptor (HR)-positive/HER2-negative HER2-Enriched (HER2-E) advanced breast cancer (BC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-28-05.