Abstract PS1-10-04: Metronomic Chemo-Endocrine Therapy with Fulvestrant and Polychemotherapy in Heavily Pretreated ER+ Breast Cancer Patients: A Single-Center Cohort Study"

Abstract Introduction: There is no doubt that the combination of endocrine drugs with CDK4/6 inhibitors, which act as phase-specific antiproliferative agents, demonstrated a striking clinical activity and became a treatment of choice in advanced ER+ breast cancer. Therefore, we have hypothesized that combining ER degrader with metronomic polychemotherapy can improve clinical outcomes in advanced, endocrine-resistant ER+ breast cancer patients. Material and methods: The treatment (FulVEC) consisted of a combination of fulvestrant (500 mg i.m. on days 1, 14, and 28, and every 4 weeks thereafter) with a VEC regimen (vinorelbine 40 mg p.o. three times a week, capecitabine 500 mg p.o. three times a day, cyclophosphamide 50 mg p.o. once a day). After local ethical committee approval, this treatment was offered initially as a salvage therapy for advanced ER+ BC patients who had exhausted all available treatment options. Further, after promising results, also for patients who refused or were ineligible for standard intravenous chemotherapy. All patients had previously received at least one line of palliative systemic therapy (40% received > 3 lines and 22% received> 5 lines). Most (53%) have previously failed fulvestrant, and 34%, 32%, and 29% have previously failed palliative treatment with capecitabine, vinorelbine and cyclophosphamide, respectively. CDK4/6i have been previously administered to 47% of patients. Most patients presented with bone (82%) and liver (66%) metastases. Three patients (8%) had OUN metastases. The median duration of previous palliative systemic treatment was 23 months. All patient’s data were collected prospectively. Results: Between 2017-2025 - 68 patients (median age 49.5 years) were treated with the FulVEC regimen in a single-center cohort study. In the general population, administration of FulVEC led to at least disease stabilization in 87% of patients and was associated with median PFS and OS of 8.5 months and 21.5 months, respectively. The 12- and 24-month PFS and OS rates were 24%, 6% and 65%, 28%, respectively. Previous treatment with CDK4/6i, fulvestrant, vinorelbine, or cyclophosphamide had no impact on patient outcomes; however, previous use of capecitabine was associated with decreased median PFS (6.5 months, HR=1.58, p=0.12). Liver metastases were associated with significantly increased risk of death (HR=2.11, p=0.02). Median OS and PFS for patients who received 3-4 and ≥5 lines of previous treatment was 7.5 and 15.6 months, and 6.5 and 16.5 months, respectively. Three patients with symptomatic OUN metastases (2 with leptomeningeal dissemination) treated with FulVEC responded to the treatment with median PFS and OS of 11.6 and 25.8 months, respectively. The FulVEC regimen was generally well tolerated, with no treatment-related toxicity necessitating cessation. Temporary treatment interruption was required in 18% of patients due to G3-4 myelotoxicity, primarily neutropenia. Dose reduction, needed in 47% of patients, was due to myelotoxicity, capecitabine-induced hand-foot-syndrome, and cyclophosphamide-induced cystitis. Conclusion: Chemo-endocrine therapy (FulVEC) comprising fulvestrant and metronomic polychemotherapy demonstrated high activity in pretreated, endocrine-refractory breast cancer patients. The activity of the FulVEC regimen compares favorably to available novel anti-cancer strategies used after failure of endocrine therapies. One of the most critical aspects of this therapy, besides its antitumor activity and safety, is its cost, which is minimal compared to novel therapeutic options considered for this patient population. A phase III trial comparing FulVEC with physician treatment of choice in patients who failed first line HTH+CDK4/6i is warranted. Citation Format: P. Wysocki, A. Buda-Nowak, &. Kwinta, A. Michalowska-Kaczmarczyk, K. Konopka, M. Lubas, M. Lobacz, M. Jurczyk, P. Potocki, M. Koniewski. Metronomic Chemo-Endocrine Therapy with Fulvestrant and Polychemotherapy in Heavily Pretreated ER+ Breast Cancer Patients: A Single-Center Cohort Study" [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 PS1-10-04.