Abstract OT-28-05: Solti-1718 NEREA trial: Neratinib in hormone receptor (HR)-positive/HER2-negative HER2-Enriched (HER2-E) advanced breast cancer (BC)
Authors: Saura Cristina , Ciruelos Eva , Vidal Maria , Garrigós Laia , Margelí Mireia , Morales Serafin , Gonzalez-Farré Xavier , Bofill Javier Salvador , Blancas Isabel , Gasent Joan M , López-Miranda Elena , Godoy Ana , Iglesias Maria , Sánchez-Rovira Pedro , Hernao Fernando , Gallegos Isabel , Pulido Catarina , Alves Sara , Branco Diogo , Passos-Coelho José , Escrivá-de-Romaní Santiago , Ferrero-Cafiero Juan M , Villagrasa Patricia , Prat Aleix 
Published: February 2021

Abstract
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 (&lt;15) or efficacy (≥28). A total of 56 evaluable patients will be included in stage I and II. The primary objective is to assess the efficacy of neratinib in combination with ET in HER2-E, HR+/HER2-negative patients in terms of PFS6 by local assessment by the investigator using RECIST v.1.1. Secondary endpoints include clinical benefit rate at 6 months, overall response rate, duration of response, time to response and incidence, duration and severity of adverse events. The Spanish national competent authority approved the study on April 8th 2020. The study will enroll patients in 15 sites in Spain and 3 sites in Portugal. Recruitment will start on July 2020. We thank PUMA BIOTECHNOLOGY, INC for their provision of Neratinib and financial contribution to the study. References: 1. Finn R, Liu Y, Martin M, Rugo H, Dieras V, Im S-A, et al. Abstract P2-09-10: Comprehensive gene expression biomarker analysis of CDK 4/6 and endocrine pathways from the PALOMA-2 study. Cancer Res. 2018;78:P2-09-10. 2. Finn RS, Martin M, Rugo HS, Jones S, Im S-A, Gelmon K, et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016;375:1925-36. 3. Prat A, Brase JC, Cheng Y, Nuciforo P, Paré L, Pascual T, et al. PAM50 intrinsic subtype in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) treated with exemestane (EXE) in combination with everolimus (EVE) or placebo (PBO): A correlative analysis of the phase III BOLERO-2 trial. European Journal of Cancer. 2018;92:S117-8.
Citation Format: Cristina Saura, Eva Ciruelos, Maria Vidal, Laia Garrigós, Mireia Margelí, Serafin Morales, Xavier Gonzalez-Farré, Javier Salvador Bofill, Isabel Blancas, Joan M Gasent, Elena López-Miranda, Ana Godoy, Maria Iglesias, Pedro Sánchez-Rovira, Fernando Hernao, Isabel Gallegos, Catarina Pulido, Sara Alves, Diogo Branco, José Passos-Coelho, Santiago Escrivá-de-Romaní, 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.