Abstract P3-01-08: Metronomic chemo-endocrine treatment (FulVEC) for patients with advanced hormone-refractory ER+ breast cancer

Abstract Introduction: The development of resistance to endocrine treatment (HTH) can result from various biological mechanisms not only related to ER function but also to activation of multiple signaling pathways, which make HTH insufficient to control cancer cells. The combination of HTH with CDK4/6 inhibitors, which largely resemble phase-specific antiproliferative cytotoxic agents, demonstrated a striking clinical activity and became a standard treatment in ER+ breast cancer. Therefore, we have hypothesized that combining HTH (ER degraded) with metronomic polychemotherapy might improve clinical outcomes in advanced, endocrine-resistant ER+ breast cancer patients. Material and methods: The treatment (FulVEC) combined fulvestrant (500 mg i.m. d 1, 14, 28, and q4w thereafter) with a VEC regimen (vinorelbine 40 mg p.o. 3x/week, capecitabine 500 mg p.o. tid, cyclophosphamide 50 mg p.o. qd). After local ethical committee approval, this treatment was initially offered as a salvage therapy for advanced ER+ BC patients who exhausted available treatment options, and latter also for patients who refused or were ineligible for standard intravenous chemotherapy. All patients were previously treated with at least 1 line of palliative systemic therapy (47% received 3+ lines and 21% 5+ lines). Most (53%) have previously failed fulvestrant, and 34%, 32%, and 29% have previously failed palliative treatment with capecitabine, vinorelbine, and cyclophosphamide, respectively. Almost half of the patients (47%) received CDK4/6i previously. Most patients presented with bone (82%) and liver (66%) metastases. Three patients (8%) had OUN metastases, and 5% showed only locally advanced disease. Results: Between 2017-2022 – 38 patients (median age 49.1 years) received the FulVEC regimen, and all data was prospectively collected. In the ITT 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. Previous treatment with capecitabine and vinorelbine was associated with non-significantly shorter PFS of 6.5 and 6.3 months, respectively. However, previous utilization with fulvestrant or cyclophosphamide had no impact on patient outcomes. Surprisingly, previous treatment with CDK4/6 inhibitors did not impact either PFS or OS (8.5 and 20.8 months, respectively). Patients with liver metastases had a higher (non-significant) risk of progression or death compared to other locations of metastases. 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. FulVEC regimen was generally well tolerated with no toxicity-related treatment cessation and temporary treatment interruption in 18% of patients due to G3-4 myelotoxicity, mainly neutropenia. Dose reduction, required 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 surprisingly high activity in pretreated, endocrine-refractory breast cancer patients. Besides its significant antitumor activity and good safety profile, one of the most critical aspects of this therapy is its cost. FulVEC regimen consists of old, widely available, and inexpensive drugs and thus costs at least a level of magnitude less than any novel, targeted therapies considered for advanced ER+ BC. FulVEC and similar affordable strategies are critical for patients from low and middle-income countries. The activity of FulVEC proves that combining chemo- and hormone therapy in a palliative setting cannot be assumed as a no-go strategy. A phase III trial comparing FulVEC with physician treatment of choice in advanced BC patients who failed first-line HTH+CDK4/6i is warranted. Citation Format: Anna Buda-Nowak, Lukasz Kwinta, Pawel Potocki, Joanna Streb, Piotr Wysocki. Metronomic chemo-endocrine treatment (FulVEC) for patients with advanced hormone-refractory ER+ breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-08.