In the first-line treatment of HER2-negative metastatic breast cancer, additional administration of the recombinant monoclonal mouse-human antibody bevacizumab (AVASTIN) prolongs median progression-free survival from 5.8 months to 11.3 months, compared to the taxane paclitaxel (TAXOL, generics) alone. At the same time, however, it increases the risk of severe adverse reactions by approximately 20% (E2100 study (1)) (2). Although there was no improvement in overall survival, bevacizumab was licensed for this indication in 2007 in Europe and in 2008 in the USA based on the E-2100-study, subject to the clinical benefit being investigated in further studies (2,3). At the time, the American medicines agency FDA went against the recommendation of its advisory committee, which voted 5:4 against approval, also because of shortcomings in the study (2).

In 2009, the European medicines agency EMA extended the authorisation to the combination with the taxane docetaxel (TAXOTERE), although the increase in median progression-free survival in the AVADO* study (4), on which the decision was based, was even smaller (3). In this study, overall survival on bevacizumab even tended to be shorter (2).

In the USA, by comparison, the application for maintaining and expanding the approval to breast cancer looks set to fail. In addition to the AVADO study, the RIBBON-1* trial, a placebo-controlled study of bevacizumab in combination with the 5-fluorouracil prodrug capecitabine (XELODA), a taxane or anthracycline-containing chemotherapy, was also presented to the FDA's advisory committee. Bevacizumab increases median progression-free survival by 2.9 months when added to capecitabine and by 1.2 months when added to a taxane or anthracycline (2). However, overall survival is not significantly affected and as in the AVADO study even tended to be shorter in the taxane group on bevacizumab (5). Severe adverse reactions were observed nearly twice as frequently on the antibody as in the placebo arms (2). For the 13 members of the FDA's advisory committee, altogether, the risks are paramount. It voted, with only one dissenting opinion, to revoke the approval for breast cancer (6). It is to be expected that the FDA will follow its advisors' recommendation this time (7). We advise against the use of bevacizumab in breast cancer, - ed.

1

MILLER, K. et al.: N. Engl. J. Med. 2007; 357: 2666-76

2

FDA Information Document Oncology Drug Advisory Committee Meeting, 20 July 2010; to be found at http://www.fda.gov/AdvisoryCommittees/ CommitteesMeetingMaterials/Drugs/ OncologicDrugsAdvisoryCommittee/ucm219223.htm

3

EMA: European Public Assessment Report (EPAR) AVASTIN, as at 4 August 2010; to be found at http://www.ema.europa.eu/htms/human/epar

4

MILES, D.W. et al.: J. Clin. Oncol. 2010; 28: 3239-47

5

FDA: Core Presentation, 20 July 2010; http://www.fda.gov/downloads/ AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ OncologicDrugsAdvisoryCommittee/UCM219978.pdf

6

Genentech: Press Release, 20 July 2010; http://www.gene.com/gene/ news/press-releases/display.do?method=print&id=12887

7

Scrip 2010; Nr. 3506: 14

*

AVADO = Avastin And Docetaxel
RIBBON 1 = Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer