Abstract PO4-14-02: Enhancing Informative Outcomes with Liquid Biopsy in a Real-World Population of Patients with Advanced Breast Cancer: Analysis of the SOLTI-1903 HOPE Study

Abstract Background: The integration of next-generation sequencing (NGS) into routine clinical practice is often hindered by financial and logistical challenges, resulting in diagnostic and therapeutic disparities among patients. Addressing these issues, the SOLTI-1903 HOPE study (NCT04497285) seeks to evaluate the feasibility of implementing a molecular screening program that actively involves patients with advanced breast cancer (ABC) in the management of their disease. By empowering patients, this study aims to gain a comprehensive understanding of the genomic landscape of ABC and to facilitate patient access to matched targeted therapies in Spain Methods: In the SOLTI-1903 HOPE study, a patient-centric approach was adopted, allowing patients living anywhere in Spain, and diagnosed with ABC, to actively lead their inclusion, participation, and follow-up using a digital tool (DT). Patients signed an informant consent, and then provided clinical information and underwent a liquid biopsy (LBx) using the Guardant360 panel at a local laboratory. LBx samples could be obtained at the moment of progressive disease (PD), when a new line of treatment was started < 8 weeks before extraction (PT), or during treatment with stable disease o partial response lasting more than 8 weeks (SD/PR). Clinical and molecular findings were evaluated by a Molecular Advisory Board (MAB), which generated a comprehensive report explaining the observed alterations and listing potentially beneficial matched targeted treatments. The primary endpoint of this subanalysis was to compare the genomic outcomes between LBx samples obtained at SD and those obtained at PD or PT. In the study, tissue samples were also collected and analysed by Foundation but this analysis will be reported in other communications. Results: From October 2020 to May 2023, a total of 273 blood samples were obtained from 253 patients diagnosed with ABC, with the majority being HR+/HER2- (81%), followed by HER2-positive (13%) and triple-negative (6%). Mean turnaround time was 10.9 days from blood collection to final result. Despite nearly 40% of patients being SD or PR, in 79.9% of the LBx (n=218), one or more genomic alterations were detected, and among these, 74.0% (n=202) were classified as pathogenic. Among the 74 genes analyzed by the Guardant360 panel, 8 genes were classified as tiers I-III according to the ESCAT levels of clinical relevance. In 150 LBx samples (54.9%), one or more pathogenic alterations were associated with ESCAT levels I-III, while only the remaining 52 LBx samples (19.1%) with pathogenic alterations were not associated with any ESCAT levels I-III. Among the analyzed LBx samples, a total of 928 distinct gene alterations were identified. Of these, 650 alterations (70.1%) were classified as pathogenic, while 278 (29.9%) were categorized as variants of unknown significance or lacked a reported impact. Notably, 25% (n=323) of the pathogenic gene alterations were further classified as ESCAT I-III. Out of the 273 LBx samples, 140 were obtained at PD, 30 at PT, and 103 at SD/PR. Circulating tumor DNA (ctDNA) was detected in 91.4% of PD samples, 86.7% of PT samples, and 62.1% of SD/PR samples (p< 0.001). Alterations classified as ESCAT levels I-III were observed in 70% of PD samples, 60% of PT samples, and 33% of SD/PR samples (p< 0.001). In 20 patients, LBx was repeated, with 16 of them having the first LBx obtained during SD/PR and the second LBx collected during PD or PT. The detection rate of ctDNA increased significantly from 18.7% (n=3) to 87.5% (n=14) (p< 0.001). The number of LBx samples with ESCAT levels I-III alterations also showed a significant increase from 12.5% (n=2) to 68.7% (n=11) (p=0.0032). Conclusions: Our findings highlight the importance of obtaining LBx samples during disease progression -compared to SD/PR- to gain greater genomic informativeness and better guide personalized treatment approaches for patients with advanced breast cancer. Citation Format: Tomás Pascual, Elia Seguí, Ruben Olivera-Salguero, Juan Miguel Cejalvo, Mafalda Oliveira, Pablo Tolosa, Maria Vidal, Marcos Malumbres, Joaquín Gavilá, Cristina Saura, Sonia Pernas, Rafael López, Mireia Margelí, Judith Balmaña, Montserrat Muñoz, Isabel Blancas, Valentina Boni, Eva Ciruelos, Elena Galve, Antonia Perelló, Rodrigo Sánchez-Bayona, Susana De La Cruz, Miguel De La Hoya, Aura Blanch-Torras, Rosana Sposito, Jordi Canes, Helena Masanas, Rosa Olmos, Margarita Forns, Maria José Prieto, Ana Casas, Aleix Prat. Enhancing Informative Outcomes with Liquid Biopsy in a Real-World Population of Patients with Advanced Breast Cancer: Analysis of the SOLTI-1903 HOPE Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-14-02.