Final results for overall survival (OS), the primary endpoint of the CECOG TURANDOT prospective randomised trial evaluating bevacizumab-paclitaxel (BEV-PAC) vs BEV-capecitabine (CAP) for HER2-negative locally recurrent/metastatic breast cancer (LR/mBC)

Background: The open-label randomised phase III TURANDOT trial aimed to demonstrate non-inferior OS with first-line BEV–CAP vs BEV–PAC for LR/mBC. The interim analysis did not confirm non-inferior OS (stratified hazard ratio [HR] 1.04; 97.5% repeated confidence interval [CI]: −∞ to 1.69) [Lang Lancet Oncol 2013]. Here we report the final OS analysis.

Methods: Patients (pts) with HER2-negative LR/mBC who had received no prior chemotherapy for LR/mBC were randomised to either BEV–PAC (BEV 10mg/kg d1 & 15 + PAC 90mg/m² d1, 8 & 15 q4w) or BEV–CAP (BEV 15mg/kg d1 + CAP 1000mg/m² bid d1–14 q3w) until disease progression or unacceptable toxicity. Stratification factors were oestrogen/progesterone receptor (ER/PgR) status, country and menopausal status. The primary objective was to demonstrate non-inferior OS with BEV–CAP vs BEV–PAC in the per-protocol (PP) population by rejecting the null hypothesis of inferiority (HR ≥1.33) using a stratified Cox proportional hazard model. Sensitivity analyses included unstratified Cox model, intent-to-treat (ITT) and subgroup analyses.

Results: At the primary final OS analysis in the PP population after deaths in 183 of 266 pts (69%) in the BEV–PAC arm and 201 of 265 (76%) in the BEV–CAP arm (median OS: 30.2 vs 26.1 months, respectively), the stratified HR was 1.02 (97.5% repeated CI: −∞ to 1.26) indicating non-inferiority. However, the unstratified Cox model (HR=1.13; 97.5% repeated CI: −∞ to 1.39) was not supportive. ITT analyses were consistent with the PP results. Subgroup results are shown in the table.

Conclusion: The primary objective was met at the final OS analysis. However, inconsistency between stratified and unstratified OS results and heterogeneity between subgroups is being explored further.

Conflict of interest: Corporate-sponsored Research: R Greil: Roche, Amgen, Celgene. G Steger: Novartis, Roche, Amgen, Teva, Celgene. T Pienkowski: Roche. D Sirbu: PSi, Verum Edu, INC Research. A Eniu: Roche, Astra Zeneca, GSK, Novartis. Other Substantive Relationships: C Zielinski: honoraria – Roche. consultancy and advisory role – Roche. Z Kahan: patents, royalties, other intellectual property – Springer. R Greil: honoraria – Roche, BMS, Celgene. consultancy and advisory role – Roche, BMS, Celgene. travel expenses – Roche. S Beslija: consultancy and advisory role – Roche. expert testimony – Roche, Abvic, Novartis. G Steger: consultancy and advisory role – Roche, Pfizer, Astra-Zeneca, Novartis, Teva, Amgen, Celgene. travel expenses – Roche, Novartis, Amgen, Teva, Celgene. B Melichar: honoraria – Roche, Novartis, GSK. consultancy or advisory role: Roche, Novartis GSK. travel expenses – Roche, Novartis, GSK: T Pienkowski: honoraria – Roche. travel expenses – Roche, Novartis. D Sirbu: consultancy or advisory role: A&D Pharma. A Eniu: honoraria – Roche, Astra Zeneca, Novartis. consultancy or advisory role: Roche, Astra Zeneca, Novartis. B Nisenbaum: travel expenses – Roche, Medison, Teva. D Messinger: employment – IST GmbH. T Brodowicz: consultancy or advisory role – Roche, Bayer, Novartis.