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)

Konference: 2015 40th Congress ESMO a 18th ECCO - účast ČR

Kategorie: Zhoubné nádory prsu

Téma: Breast Cancer - Advanced Disease

Číslo abstraktu: 1800

Autoři: Prof. Dr. Christoph C. Zielinski; Prof. Dr. István Lang; Prof. Moshe Inbar; MD Zsuzsanna Kahan, PhD.; MD Richard Greil, Ph.D.; Dr. Semir Beslija; Dr. Salomon M. Stemmer; Dr. Zaneta Zvirbule; Prof. MD Günther Steger; prof. MUDr. Bohuslav Melichar, Ph.D.; Dr. Tadeusz Pienkowski; Dr. Daniela Sirbu; prof. MUDr. Luboš Petruželka, CSc.; Dr. Alexandru Eniu; Bella Nisenbaum; Magdolna V. Dank; Rodica Anghel; Diethelm Messinger, MSc; prof. MD Thomas Brodowicz

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.

Table (abstract 1800).
Factor Subgroup, PP population Median OS, months Unstratified HR (95%CI)
Hormone receptor status ER and/or PgR positive (n=406) 30.5 27.6 1.07 (0.85–1.35)
  Triple negative (n=124) 24.4 17.7 1.35 (0.90–2.02)
Female menopausal status Pre (n=95) 27.6 23.0 1.75 (1.08–2.84)
  Post (n=431) 30.3 26.1 1.04 (0.83–1.29)
ECOG performance status 0 (n=350) 32.6 31.4 1.07 (0.83–1.39)
  1/2 (n=181) 20.9 20.5 1.23 (0.90–1.69)
Age, years <65 (n=393) 27.4 26.0 1.07 (0.85–1.35)
  ≥65 (n=138) 34.5 26.5 1.30 (0.86–1.95)
Visceral metastases Yes (n=365) 26.2 23.7 1.07 (0.85–1.36)
  No (n=166) 35.4 30.9 1.20 (0.82–1.75)
Prior anthracycline and/or taxane Yes (n=285) 28.5 24.3 1.09 (0.83–1.43)
  No (n=246) 32.3 28.0 1.16 (0.86–1.57)
Body surface area, m2 <1.8 (n=322) 26.9 27.2 0.94 (0.72–1.22)
  ≥1.8 (n=209) 31.6 22.5 1.53 (1.11–2.12)


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.

Metastatic Breast Cancer

Datum přednesení příspěvku: 27. 9. 2015