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Lancet Oncol. 2014 Oct;15(11):1269-78. doi: 10.1016/S1470-2045(14)70439-5. Epub 2014 Sep 28.

Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial.

Author information

1
German Breast Group, Neu-Isenburg, and University Women's Hospital, Frankfurt, Germany. Electronic address: Gunter.vonMinckwitz@germanbreastgroup.de.
2
University Hospital of Udine, Udine, Italy.
3
Vall d'Hebron Institute of Oncology and Vall d'Hebron University Hospital, Barcelona, Spain.
4
Center of Oncology, University Hospital Split, Split, Croatia.
5
Outpatient Cancer Center, Freiburg, Germany.
6
Department of Medicine I and Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria; Central European Cooperative Oncology Group, Vienna, Austria.
7
Centre Hospitalier-Universitaire de Besançon, Besançon, France.
8
Institut du Cancer Montpellier, Val d'Aurelle, France.
9
National Institute of Oncology, Budapest, Hungary.
10
Hospital Universitario 12 Octubre, Madrid, Spain.
11
Istituto Nazionale Tumori Fondazione G Pascale, Naples, Italy.
12
Centre Henri Becquerel, Rouen, France.
13
F Hoffmann-La Roche Ltd, Basel, Switzerland.
14
Assistance-Publique Hôpitaux de Paris-Tenon, Institut Universitaire de Cancerologie Université Pierre et Marie Curie, Sorbonne Université, Paris, France.

Abstract

BACKGROUND:

Combining bevacizumab with first-line or second-line chemotherapy improves progression-free survival in HER2-negative locally recurrent or metastatic breast cancer. We assessed the efficacy and safety of further bevacizumab therapy in patients with locally recurrent or metastatic breast cancer whose disease had progressed after treatment with bevacizumab plus chemotherapy.

METHODS:

In this open-label, randomised, phase 3 trial, we recruited patients who had HER2-negative locally recurrent or metastatic breast cancer that had progressed after receiving 12 weeks or more of first-line bevacizumab plus chemotherapy from 118 centres in 12 countries. Patients were randomly assigned (1:1) by use of a central interactive voice response system using a block randomisation schedule (block size four) stratified by hormone receptor status, first-line progression-free survival, selected chemotherapy, and lactate dehydrogenase concentration, to receive second-line single-agent chemotherapy either alone or with bevacizumab (15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks). Second-line therapy was continued until disease progression, unacceptable toxicity, or consent withdrawal. At progression, patients randomly assigned to chemotherapy alone received third-line chemotherapy without bevacizumab; those randomly assigned to bevacizumab continued bevacizumab with third-line chemotherapy. The primary endpoint was progression-free survival from randomisation to second-line progression or death in the intention-to-treat population. This trial is ongoing, and registered with ClinicalTrials.gov, number NCT01250379.

FINDINGS:

Between Feb 17, 2011, and April 3, 2013, 494 patients were randomly assigned to treatment (247 in each group). The median duration of follow-up at the time of this prespecified primary progression-free survival analysis was 15·9 months (IQR 9·1-21·7) in the chemotherapy-alone group and 16·1 months (10·6-22·7) in the combination group. Progression-free survival was significantly longer for those patients treated with bevacizumab plus chemotherapy than for those with chemotherapy alone (median: 6·3 months [95% CI 5·4-7·2] vs 4·2 months [3·9-4·7], respectively, stratified hazard ratio [HR] 0·75 [95% CI 0·61-0·93], two-sided stratified log-rank p=0·0068). The most common grade 3 or more adverse events were hypertension (33 [13%] of 245 patients receiving bevacizumab plus chemotherapy vs 17 [7%] of 238 patients receiving chemotherapy alone), neutropenia (29 [12%] vs 20 [8%]), and hand-foot syndrome (27 [11%] vs 25 [11%]). Grade 3 proteinuria occurred in 17 (7%) of 245 patients receiving combination therapy and one (<1%) of 238 patients receiving chemotherapy alone. Serious adverse events were reported in 61 (25%) of 245 patients receiving bevacizumab plus chemotherapy versus 44 (18%) of 238 patients receiving chemotherapy alone.

INTERPRETATION:

These results suggest that continued VEGF inhibition with further bevacizumab is a valid treatment option for patients with locally recurrent or metastatic HER2-negative breast cancer whose disease was stabilised or responded to first-line bevacizumab with chemotherapy.

FUNDING:

F Hoffmann-La Roche.

PMID:
25273342
DOI:
10.1016/S1470-2045(14)70439-5
[Indexed for MEDLINE]

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