353O - Efficacy and safety in TANIA, a randomised phase III trial of continued or reintroduced bevacizumab (BEV) after 1st-line BEV for HER2-negative loca...

Date 28 September 2014
Event ESMO 2014
Session Breast cancer, metastatic
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Gunter von Minckwitz
Citation Annals of Oncology (2014) 25 (suppl_4): iv116-iv136. 10.1093/annonc/mdu329
Authors G. von Minckwitz1, F. Puglisi2, J. Cortes3, E. Vrdoljak4, N. Marschner5, C. Zielinski6, C.B. Villanueva7, G. Romieu8, I. Láng9, E. Ciruelos10, M. De Laurentiis11, C. Veyret12, S. de Ducla13, U. Freudensprung14, S. Srock13, J. Gligorov15
  • 1Managing Director, German Breast Group and University Women's Hospital, 63263 - Neu-Isenburg/DE
  • 2Dipartimento Di Oncologia, Azienda Ospedaliero-Universitaria di Udine, Udine/IT
  • 3Breast Cancer Program, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 4Medical Oncology, Center of Oncology and Radiotherapy, HR-21000 - Split/HR
  • 5Internal Medicine / Hematology, Praxis für Interdisziplinaere Onkologie, 79106 - Freiburg/DE
  • 6Department Of Medicine I, Medical University of Vienna and Central European Cooperative Oncology Group (CECOG), A-1090 - Vienna/AT
  • 7Service Oncologie Medicale, C.H.U. Jean Minjoz, FR-25030 - Besancon CEDEX/FR
  • 8Oncologie Médicale, Centre Val d'Aurelle, Montpellier/FR
  • 9Dept. Med. Oncology And Clin. Pharmacology B, National Institute of Oncology, HU-1122 - Budapest/HU
  • 10Medical Oncology, Hopital 12 de Octubre, Madrid/ES
  • 11Medical Oncology, INT Fondazione G Pascale, Naples/IT
  • 12Medical Oncology, Centre Henri Becquerel, Rouen/FR
  • 13Medical Affairs, F Hoffman-La Roche Ltd, Basel/CH
  • 14Global Medical Affairs Biometrics, F Hoffmann-La Roche Ltd, 4070 - Basel/CH
  • 15Oncologie Medicale, APHP, CancerEst, Tenon University Hospital, 75020 - Paris/FR

Abstract

Aim

Combining BEV with 1st- or 2nd-line chemotherapy (CT) improves progression-free survival (PFS) in HER2-negative LR/mBC. The open-label randomised phase III TANIA trial evaluated further BEV in BEV-pretreated LR/mBC.

Methods

Patients (pts) whose HER2-negative LR/mBC had progressed during/after ≥12 weeks of 1st-line BEV + CT were randomised 1:1 to 2nd-line single-agent CT either alone or with BEV (15 mg/kg q3w or 10 mg/kg q2w). Stratification factors were: hormone receptor status; time to 1st-line progression (PD; <6 vs ≥6 mo); CT choice (taxane vs non-taxane vs vinorelbine); and LDH (≤1.5 vs >1.5 × upper normal limit). 2nd-line therapy was continued until PD, unacceptable toxicity or consent withdrawal. At PD, pts in the CT arm received 3rd-line CT without BEV (no crossover); pts initially randomised to CT + BEV received 3rd-line CT + BEV. The primary endpoint was PFS from randomisation to 2nd PD/death. Additional endpoints included 2nd-line PFS in prespecified subgroups, 2nd- and 3rd-line PFS (randomisation to 3rd PD/death), 2nd-line objective response rate, overall survival (OS), safety, QoL and biomarkers. Sample size was calculated based on a log-rank test assuming median PFS of 7 → 9.3 mo and a HR of 0.75. PFS events were required in 384 of 488 pts for 80% power at 2-sided α = 0.05.

Results

From Jan 2011 to Apr 2013, 494 pts were enrolled (247 CT; 247 CT + BEV). Baseline characteristics, CT vs CT + BEV: median age 54 vs 56 y; triple negative 23% vs 20%; disease-free interval ≤12 mo 10% vs 7%. The most frequently chosen 2nd-line CT was capecitabine (59% vs 61%).

CT (N = 247) CT + BEV (N = 247)
Median follow-up, mo 15.9 16.1
2nd-line PFS (primary endpoint)
Events, n (%) 203 (82) 204 (83)
Median 2nd-line PFS, mo 4.2 6.3
Stratified HR (95% CI) 0.75 (0.61–0.93) p = 0.0068a
Best objective response rate, % (95% CI) 16.8 (11.7–22.9) 20.9 (15.2–27.5)
Difference (95% CI) 4.1 (–4.2 to 12.4) p = 0.3457b
2nd-line grade ≥3 adverse events of special interest, %c (N = 238) (N = 245)
Hypertension 7.1 13.5
Proteinuria 0.4 6.9
Venous thromboembolic event 2.1 3.3
Febrile neutropenia 1.7 3.3
Congestive heart failure 0.4 2.0
Bleeding 1.7 0.4
Arterial thromboembolic event 1.3 0
Wound-healing complication 0 0.8
Gastrointestinal perforation 0 0.4
Fistula/abscess 0 0

a2-sided stratified log-rank test. b2-sided chi-squared test with Schouten correction. cBEV basket terms, MedDRA v16.1. Data cut-off: 20 Dec 2013.

Conclusions

The primary objective was met, showing statistically significantly improved PFS with BEV after PD on 1st-line BEV-containing therapy. 2nd-line safety results were as expected from previous BEV trials in LR/mBC. Final OS, 2nd and 3rd-line PFS and 3rd-line safety results are due in 2015.

Disclosure

G. von Minckwitz: is a paid member on Roche's advisory boards, and has received speaker honoraria and conducted Roche-sponsored research; F. Puglisi: has received honoraria from Roche; J. Cortes: has received honoraria from Roche, Celgene, Novartis and Eisai and has acted as a consultant for Roche and Celgene; E. Vrdoljak: is a member of Roche advisory boards and has received corporate sponsored research; N. Marschner:is a member of Roche advisory boards and has received corporate sponsored research; C. Zielinski: has received speaker honoraria Roche, Eli Lilly and Pfizer; G. Romieu: is a member of a Roche Advisory Board; M. De Laurentiis: has received honoraria for talks, seminars and Advisory Board participation from Roche; C. Veyret: is an expert member of Roche Boards; S. De Ducla: is an employee of, and holds stock in Roche; U. Freudensprung: is an employee of F. Hoffmann-La Roche Ltd S. Srock: SS is an employee of, and holds stock in Roche; J. Gligorov: has acted as a Consultant/Advisor for, and has received honoraria and research funding from Roche. All other authors have declared no conflicts of interest.