Metastatic breast cancer (BC) has a poor prognosis with a 15-year cause-specific survival rate between 7% and 8,3%. The median overall survival approaches two years and is even shorter in women with triple-negative disease.
Bevacizumab, a recombinant humanised monoclonal IgG1 antibody, binds to the vascular endothelial growth factor (VEGF) and neutralises its biological activity, thus inhibiting the vascularisation of tumours.
Bevacizumab has currently no market approval for the second-line therapy of metastatic BC in combination with chemotherapy, neither in the US nor in Europe.
Two phase III trials were identified for this indication of bevacizumab.
The first study (Miller et al.) compared the combination of bevacizumab and capecitabine as second-line and third-line therapy to capecitabine monotherapy in 462 heavily pre-treated women, including also about a quarter of patients with HER2-positive BC.
Bevacizumab did not improve the primary endpoint progression free survival (PFS), duration of survival or any other reported outcome except for the objective response rate. There was also no difference in time to deterioration in quality-of-life. In terms of adverse events (AEs), Miller et al found similar results between the two treatment groups, including AEs leading to study discontinuation.
The RIBBON-2 study, the other phase III trial, evaluated only second-line bevacizumab in combination with different chemotherapeutic regimens in 684 women with metastatic HER2-negative BC.
The primary endpoint, PFS, was significantly different and showed an absolute gain of 2.1 months for bevacizumab. Subgroup analyses indicated further improvements for women with triple-negative BC or for patients who received taxanes as chemotherapy. All other endpoints however, including overall survival, did not differ significantly between the groups. Quality-of-Life was not addressed in this trial.
AEs of at least grade 3 (severe, life-threatening or leading to death) occurred more often in the combination arm than in the chemotherapy only arm, and those leading to treatment discontinuation were also more frequent in the bevacizumab group.
Whether bevacizumab in combination with chemotherapy will be used for second-line therapy in metastatic BC depends on its trade-off between AEs and benefit in terms of improving symptoms, survival and quality of life. For that, above all, convincing data on the quality-of-life as well as on special subgroups are needed.