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 {"type":"clinical-trial","attrs":{"text":"NCT00600340","term_id":"NCT00600340"}}NCT00600340).