Metronomic cyclophosphamide and capecitabine combined with lapatinib in heavily pretreated metastatic breast cancer (MBC) HER2-positive patients: 2-year update.

Abstract

e11515 Background: Current therapeutic goals for MBC, as an incurable disease, are symptoms and prolonged disease control together with good quality of life. Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. We evaluated the efficacy and tolerability of the combination of anti-angiogenetic activity of metronomic chemotherapy with a tyrosine kinase inhibitor such as lapatinib in heavily pre-treated MBC HER-2 positive patients. Methods: Metastatic breast cancer patients HER-2 positive with CEA or Ca15.3 elevated, prior systemic therapy for advanced disease, ECOG performance status < 1 and life expectancy longer than 3 months. MBC patients were treated with metronomic oral capecitabine (1500 mg daily) and cyclophosphamide (50 mg daily) plus lapatinib (1250 mg daily). The treatment was given until disease progression. Primary objective was time to progression (TTP) and safety. Results: Fifteenpatients were included. Median age was 52 years old (range 42-77). Median number of previous chemotherapy lines was 5 (range 2-10). Median time to tumor progression was 6 months (2-14). No complete response was observed. Eight out of fiftten patients (60%) with pre-existing only bone metastases achieved a stable disease and/or partial response and were still on treatment after 6 month of therapy. At the same time 100% of these patients exhibited significant reduction of serum marker concentrations. No grade 3-4 skin toxicity was reported. Hematological and gastro-intestinal toxicity was well tolerated (G1-2). No reduction of dose was needed. Conclusions: The combination of lapatinib with metronomic chemotherapy may lead to effective palliation despite extensive pretreatment at least in bone metastatic patients. The treatment appears to be less toxic than lapatinib and capecitabine at full dosage, especially in heavily pretreated MBC patients. The preliminary results suggest the need of a clinical trial to confirm a role of this combination to delay lapatinib resistance.