First results of TURANDOT Trial

Comparing two bevacizumab-containing regimens as first-line therapy for HER2 negative metastatic breast cancer

Professor Christoph Zielinski from the Comprehensive Cancer Centre, Vienna, Austria, presented the first efficacy results from the phase 3 study run by the Central European Cooperative Oncology Group (CECOG). The presentation was entitled the ‘capeciTabine and bevacizUmab Randomised Against avastiN anD taxOl Trial’ (TURANDOT). The study compared two bevacizumab-containing regimens as first-line therapy for HER2 negative metastatic breast cancer.

Prof. Zielinski reported results from a preplanned analysis of data at 19 months from this phase 3 trial of bevacizumab plus either paclitaxel or capecitabine as first-line therapy for patients with HER2 negative breast cancer. The primary objective was to demonstrate non-inferior overall survival with bevacizumab/capecitabine vs bevacizumab/paclitaxel. Interim and final overall survival analyses were planned after 175 and 389 deaths, respectively, in the per-protocol population to reject the null hypothesis of inferiority (hazard ratio [HR] ≥1.33) with 80% power and overall α = 0.025. Secondary endpoints included response rate, progression-free survival, safety and quality of life.

In TURANDOT study, chemotherapy naive patients were randomized to placebo or one of two bevacizumab regimens; 10 mg/kg d1 bevacizumab plus 90 mg/m2 d1 paclitaxel four times weekly or 15 mg/kg d1 bevacizumab plus 1000 mg/m2 bid capecitabine three times per week until disease progression or unacceptable toxicity occurred. Patients’ baseline characteristics were similar in both arms.

The trial’s primary endpoint, non-inferiority in overall survival was not met at the level of statistical significance. The pre-planned interim analysis done at a median of 19 months post-treatment showed one year overall survival rates of 81% in 285 patients treated with bevacizumab plus paclitaxel and 79% in 279 patients receiving the bevacizumab/capecitabine combination hazard ratio 1.04 (−∞ to 1.69); p = 0.0593. The response rate was 44% and 27%, in the two arms, respectively (p = 0.0001). Progression-free survival in the bevacizumab/paclitaxel and bevacizumab/capecitabine arms was median 11 months and 8.1 months, respectively (p = 0.0052).

No safety issues were raised; adverse events were consistent with the known safety profiles of all three drugs. The most common adverse events of grade ≥3 were neutropenia (18%), peripheral neuropathy (14%) and leucopenia (7%) in patients receiving bevacizumab plus paclitaxel while hand-foot syndrome (16%), hypertension (6%) and diarrhoea (5%) occurred with bevacizumab/capecitabine.

Final results from this trial are anticipated in 2014.

Professor Zielinski, commented “While seeing a significantly better progression free survival and overall response rate with paclitaxel + bevacizumab regimens in this randomised controlled trial, the interim analysis shows that overall survival was most probably not compromised by the use of capecitabine + bevacizumab as compared to the other regimen. This is particularly remarkable, as overall survival and its comparison between the two study arms was the primary end point of the study.”