Selecting first-line bevacizumab-containing therapy for advanced breast cancer: TURANDOT risk factor analyses

Background: The randomised phase III TURANDOT trial compared first-line bevacizumab-paclitaxel (BEV-PAC) vs bevacizumab-capecitabine (BEV-CAP) in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). The interim analysis revealed no difference in overall survival (OS; primary end point) between treatment arms; however, progression-free survival (PFS) and objective response rate were significantly superior with BEV-PAC. We sought to identify patient populations that may be most appropriately treated with one or other regimen.Methods:Patients with HER2-negative LR/mBC who had received no prior chemotherapy for advanced disease were randomised to either BEV-PAC (bevacizumab 10 mg kg^-1 days 1 and 15 plus paclitaxel 90 mg m^-2 days 1, 8 and 15 q4w) or BEV-CAP (bevacizumab 15 mg kg^-1 day 1 plus capecitabine 1000 mg m-2 bid days 1-14 q3w). The study population was categorised into three cohorts: triple-negative breast cancer (TNBC), high-risk hormone receptor-positive (HR+) and low-risk HR+. High-and low-risk HR+ were defined, respectively, as having ≥2 vs ≤1 of the following four risk factors: disease-free interval ≤24 months; visceral metastases; prior (neo)adjuvant anthracycline and/or taxane; and metastases in ≥3 organs. Results: The treatment effect on OS differed between cohorts. Non-significant OS trends favoured BEV-PAC in the TNBC cohort and BEV-CAP in the low-risk HR+ cohort. In all three cohorts, there was a non-significant PFS trend favouring BEV-PAC. Grade ≥3 adverse events were consistently less common with BEV-CAP. Conclusions: A simple risk factor index may help in selecting bevacizumab-containing regimens, balancing outcome, safety profile and patient preference. Final OS results are expected in 2015 (ClinicalTrials.gov NCT00600340).