Abstract OT-26-04: Solti-1801. Analysis of the efficacy of CDK4/6 inhibitors in combination with hormonal treatment in luminal breast cancer in relation to the intrinsic subtype and markers of immunity (CDK-PREDICT)
Authors: Tolosa Pablo , Pascual Tomás , Hernando Cristina , Servitja Sonia , Abad María Fernández , Villanueva Rafael , Henao Fernando , Benítez Javier , Lema Laura , Martínez Mario , Ruano Yolanda , Parrilla Lucía , Bernardini Alejandra , Roncero Ana María , Paré Laia , Canes Jordi , Salvador Fernando , Villagrasa Patricia , Prat Aleix , Ciruelos Eva 
Published: February 2021

Abstract
Introduction. The incorporation of cyclin-dependent kinase inhibitors 4 and 6 (CDK4/6 inhibitors) with endocrine therapy in patients with advanced hormone receptor-positive (HR+) breast cancer and without overexpression of the HER2 (HER2-) oncogene has demonstrated its efficacy improving progression-free survival (PFS), overall response rate (ORR) and, more recently, overall survival (OS). However, patients eventually progress due to resistance to treatment. To date, no clinical or molecular markers defining the HR +/HER2- patient population that obtains the greatest benefit from these drugs have been found, apart from estrogen receptor positivity. However, there are data from multiple retrospective analysis suggesting that within HR+/ HER2- disease, the non-luminal intrinsic subtypes (20-30% of these patients) have a worse prognosis and may not benefit from CDK4/6 inhibitors. Furthermore, the prognostic impact of tumor infiltrating lymphocytes (TILs) and gene expression related to the immune response in the context of HR + / HER2- advanced breast cancer have not been deeply investigated.
Design. CDK-PREDICT is an observational, non-interventional, multicenter study that will include 114 patients with advanced breast cancer who have received, are receiving or are going to receive endocrine therapy plus a CDK4/6 inhibitor for, at least, 8 weeks as first-line treatment. The primary objective is to correlate the intrinsic subtypes (defined by PAM50) with the efficacy (measured as PFS) of CDK4/6 inhibitors + hormone therapy. As secondary objectives, the correlation of the intrinsic subtypes with ORR and with the histopathological characteristics of the tumor will be analyzed. In addition, the expression of immune response and cell cycle genes, as well as the presence of TILs, will be correlated with the intrinsic subtypes and with PFS and ORR. Overall, we aim to develop a predictive score combining clinical, genomic and immune expression data integrating tumor biology and microenvironment. For inclusion in the study, a metastatic sample taken within 90 days prior to CDK4/6 inhibitors treatment will be required. Once this sample has been collected, registered and assessed for quality, patients will be followed up every 6 months until disease progression, death or withdrawal from the study.
This project has received a research grant from “Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad” (Spain) awarded within the National Research Program with reference PI 18/01408, co-funded with European Union ERDF funds (European Regional Development Fund). This study is included within the Biomarker program of SOLTI. Recruitment of this study started in June 2020.
Citation Format: Pablo Tolosa, Tomás Pascual, Cristina Hernando, Sonia Servitja, María Fernández Abad, Rafael Villanueva, Fernando Henao, Javier Benítez, Laura Lema, Mario Martínez, Yolanda Ruano, Lucía Parrilla, Alejandra Bernardini, Ana María Roncero, Laia Paré, Jordi Canes, Fernando Salvador, Patricia Villagrasa, Aleix Prat, Eva Ciruelos. Solti-1801. Analysis of the efficacy of CDK4/6 inhibitors in combination with hormonal treatment in luminal breast cancer in relation to the intrinsic subtype and markers of immunity (CDK-PREDICT) [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-26-04.