Abstract OT2-19-03: 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 , Brasó-Maristany Fara , Benítez Javier , Lema Laura , Martínez Mario , Ruano Yolanda , Parrilla Lucía , Bernardini Alejandra , Roncero Ana María , Paré Laia , Canes Jordi , Villagrasa Patricia , Salvador Fernando , Prat Aleix , Ciruelos Eva 
Published: March 2022

Abstract
Introduction. The incorporation of cyclin-dependent kinase inhibitors 4 and 6 (CDK4/6 inhibitors) with endocrine therapy in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer 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, data from multiple retrospective analysis suggest that within HR+/HER2- disease, the non-luminal intrinsic subtypes (20-30% of these patients) have a worse prognosis and may not benefit equally from every CDK4/6 inhibitor (Finn SABCS 2017, Prat. JCO 2021). 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 treated in first-line with CDK4/6 inhibitors + hormone therapy. The primary objective is to correlate the baseline 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. Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples will be hematoxylin and eosin (H&E) stained and percentage of TILs will be determined. RNA will be purified and analyzed at the nCounter (Nanostring Technologies) using a panel of 72 genes including the PAM50 genes and immune genes such as PD1, PDL1, CD8 or CD4. 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 100 days prior to CDK4/6 inhibitors treatment is 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. As of July 2021, 80 patients have been included at 5 sites in Spain. This study is included within the Biomarker program of SOLTI. Recruitment of this study started in June 2020. Acknowledgements.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).
Citation Format: Pablo Tolosa, Tomás Pascual, Cristina Hernando, Sonia Servitja, María Fernández Abad, Fara Brasó-Maristany, Javier Benítez, Laura Lema, Mario Martínez, Yolanda Ruano, Lucía Parrilla, Alejandra Bernardini, Ana María Roncero, Laia Paré, Jordi Canes, Patricia Villagrasa, Fernando Salvador, 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 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-19-03.