Abstract PS2-04-22: Real world data of primary resistance to cyclin-dependent kinase 4/6 inhibitors treatment in hormone-receptor positive metastatic breast cancer

Abstract Background: Around 30% of patients (pts) with breast cancer develops metastases and 70 % of pts with metastatic breast cancer (MBC) are hormone-receptor (HR)-positive/HER2-negative. Endocrine therapy (ET) combined with cyclin-dependent kinase 4/6 inhibitors (CDKi) has become the standard of care in this setting, except in cases of life-threatening disease. However, a major challenge is to overcome endocrine resistance, either primary or secondary, which limits the long-term efficacy of ET and worsens prognosis. Methods: Here, we analysed the clinical characteristics of pts at our hospital who develop primary resistance to CDKi plus ET for MBC. In a cohort of 180 pts who received ET plus CDKi for MBC between 2017-2024 in Hospital Parc Taulí, we identified 46 pts with primary resistance in the metastatic setting so we conducted a retrospective observational study to analyse clinical, treatment, efficacy and survival variables on this group of pts. We defined primary resistance as a relapse within 2 years of adjuvant ET or disease progression during the first 6 months of first-line ET for MBC and secondary resistance as a relapse that occurs after at least 2 years of adjuvant ET or within the first year after its ending. Results: 46 patients (pts) were included, median age was 52 years, 52 % were postmenopausal and 44 % had high-proliferation disease. At the diagnosis 80% had early disease and among these, 33 % received adjuvant chemotherapy and 84 % received adjuvant ET. In this group who received adjuvant treatment, 5 pts (16%) had primary resistance, 24 (77%) secondary resistance and only 2 pts had ET sensitivity. Only 7 pts (15%) in the cohort were treatment naïve. As CDKi 65% received Palbociclib, 26% Abemaciclib an 9% Ribociclib. As ET 2% received Anastrozol, 2% Exemestano, 56% Fulvestrant and 40% Letrozol. ET plus CDKi was received as first line in 41% of the pts and in 59% as second line or beyond. The majority of patients received CDKi as second-line therapy since, at the beginning of this study, they were not yet approved for first-line use.Among those treated in second line or beyond, 48 % had ET and 52 % chemotherapy as first-line treatment. Overall median progression free survival was 3 months, 4 months in pts with primary resistance in the adjuvant setting, 3 months in pts with secondary resistance, and 2 months in hormone sensivity pts (p=0.231). Median overall survival (OS) was 9 months. In the subgroup analysis, median OS was 13 months for previous primary resistance, 8 months for secondary resistance, and 12 months for hormone sensivity pts (p=0.276). Of note, OS was 8 months in pts who received CDKi as first-line and 11 months in the second line or beyond (p=0.579). This may be due to the fact that there were no patients with previous secondary resistance in the second-line or beyond group. Conclusions: Findings from this cohort suggest that pts with primary resistance in the metastatic setting has poor outcomes and supports the data that in this context pts with previous primary resistance has better results that pts with secondary resistance in the adjuvant setting, similar to the findings in the MONARCH 2 trial. One limitation of this real world data is that this is a small group of pts and the lack of PIK3CA mutation determination which is not currently analysed routinely prior to starting first-line treatment. Citation Format: O. Cano i Cano, M. Fragío Gil, A. Carrasco Navas, M. Busquets Godall, A. Ribas Bravo, O. Civit Figueras, C. Marin, J. Sandoval Alves, I. Gallego Bernardo, M. Monroe Rivera, S. Karzazi Casin, J. Arqué Garrido, M. Sierra Boada, S. Soriano Sánchez, J. Giner Joaquin, P. Ribera Fernandez, L. Vilà Martínez, R. Querol Niñerola, T. Bonfill Abella, E. Gallardo Diaz, L. Medina Ortega, B. Calvo Martinez, M. Rosich Peris, L. Soriano Gutierrez, S. Redondo Capafons, N. Gaztelumendi Corcoles, P. Andreu Cobo, G. Llort Pursals, E. Dalmau Portulas, M. Seguí Palmer, L. Fernández-Morales. Real world data of primary resistance to cyclin-dependent kinase 4/6 inhibitors treatment in hormone-receptor positive metastatic breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-04-22.