As reported in The Lancet Oncology by Christoph Zielinski, MD, of the Medical University of Vienna and the Central European Cooperative Oncology Group, and colleagues, the final results of the phase III TURANDOT trial showed that overall survival with first-line bevacizumab (Avastin)/capecitabine was noninferior vs bevacizumab/paclitaxel in per-protocol analysis among patients with advanced HER2-negative breast cancer.
The previously reported interim analysis from the trial showed that progression-free survival (secondary endpoint) was significantly better with bevacizumab/paclitaxel; there was no significant difference in overall survival, but noninferiority of bevacizumab/capecitabine could not be confirmed.
In the open-label trial, patients with locally recurrent or metastatic disease from 51 sites in Hungary, Israel, Austria, Romania, Czech Republic, Poland, Latvia, Bosnia, Slovakia, Serbia, Bulgaria, and Croatia were randomized to receive approved regimens of bevacizumab/paclitaxel or bevacizumab/capecitabine. Treatments consisted of bevacizumab at 10 mg/kg on days 1 and 15 plus paclitaxel at 90 mg/m2 on days 1, 8, and 15 every 4 weeks vs bevacizumab at 15 mg/kg on day 1 plus capecitabine at 1,000 mg/m2 twice daily on days 1 to 14 every 3 weeks. Randomization was stratified by estrogen or progesterone receptor status, country, and menopausal status.
The primary objective was demonstrating noninferior overall survival with bevacizumab/capecitabine vs bevacizumab/paclitaxel in the per-protocol population by rejecting the null hypothesis of inferiority (hazard ratio [HR] ≥ 1.33) on a stratified Cox proportional hazard model. A total of 564 patients were randomized; the per-protocol population consisted of 531 patients, including 266 in the bevacizumab/paclitaxel group and 265 in the bevacizumab/capecitabine group.
Overall Survival and Adverse Events
At the final overall survival analysis, median overall survival was 30.2 months in the bevacizumab/paclitaxel group vs 26.1 months in the bevacizumab/capecitabine group. The stratified hazard ratio was 1.02 (97.5% repeated confidence interval [RCI] of –∞ to 1.26, repeated P = .0070), indicating noninferiority. The unstratified Cox model yielded a hazard ratio of 1.13 (97.5% RCI of –∞ to 1.39, repeated P = .061), not supporting noninferiority. Intent-to-treat analyses were consistent with the per-protocol results. Median progression-free survival was 10.9 vs 8.1 months (stratified HR = 1.32, P = .0066).
The most common grade ≥ 3 adverse events among all randomized patients were neutropenia (19% vs 2%), hand-foot syndrome (< 1% vs 16%), peripheral neuropathy (14% vs < 1%), leukopenia (7% vs < 1%), and hypertension (4% vs 6%). Serious adverse events occurred in 23% vs 25%. Deaths in two patients (1%) in the bevacizumab/paclitaxel group were considered to be related to treatment.
The investigators concluded: “Bevacizumab plus capecitabine represents a valid first-line treatment option for HER2-negative locally recurrent or metastatic breast cancer, offering good tolerability without compromising overall survival compared with bevacizumab plus paclitaxel. Although progression-free survival with the bevacizumab plus capecitabine combination is inferior to that noted with bevacizumab plus paclitaxel, we suggest that physicians should consider possible predictive risk factors for overall survival, individual’s treatment priorities, and the differing safety profiles.”
The study was funded by Roche. ■