Triple negative breast cancer (TNBC) is a heterogeneous classification to which various subtypes are included. At present, TNBC lacks a standard targeted therapeutic strategy, other than conventional cytotoxic agents. The combination of weekly carboplatin and paclitaxel is active and well tolerated. In addition, bevacizumab when added to paclitaxel prolonged progression-free survival (PFS) in metastatic breast cancer (MBC). We investigated the activity and toxicity of paclitaxel plus carboplatin and bevacizumab as first-line treatment in triple-negative MBC.
The primary endpoint was the objective response rate (ORR) [complete (CR) + partial remission (PR)] and safety of the combination. The study followed the Simon's two-stage optimal design with 16 patients initially evaluated for response and toxicity and then expanding to a total of 46 patients. The null hypothesis that the objective response rate is ≤40% could be rejected if the number of CR/PR was ≥23. Paclitaxel 90mg/m2 and carboplatin AUC 2 were administered on days 1, 8, and 15 every 4 weeks, preceded by bevacizumab 10 mg/kg on days 1 and 15.
Forty-five women with triple negative MBC have been recruited thus far. Of them, 13 were premenopausal and 27 had prior (neo-) adjuvant chemotherapy. The median cycles administered were 6 (range: 1-8). We observed 7 CR, 23 PR for an ORR of 66.7%. Seven patients achieved stable disease, while 8 had disease progression. Median duration of response was 18.2 months and median PFS 10.3 months. Median overall survival was 25.7 months and 1-year survival 75.6%. Neutropenia grade 3 and 4 was experienced by 13 (29,5%) and 6 (13,6%) patients respectively, with one toxic death due to febrile neutropenia. Other grade 3 toxicities included anemia/neurotoxicity (4,4%), thrombocytopenia/diarrhea (2,2%).
Our study has achieved the primary objective of demonstrating clinical activity for weekly carboplatin and paclitaxel in combination with bevacizumab in triple negative MBC. We believe the combination merits further evaluation in this population.
Clinical trial identification
Legal entity responsible for the study
Hellenic Oncology Research Group (HORG)
All authors have declared no conflicts of interest.