TUESDAY, July 10, 2012 (MedPage Today) — The angiogenesis inhibitor bevacizumab (Avastin) has "at best" a modest effect on outcomes in metastatic breast cancer, authors of a systematic review concluded.
Despite statistically significant improvements in progression-free survival (33 percent) and response rate (15 percent), patients treated in first or second line with bevacizumab lived no longer than their counterparts treated without the targeted agent, according to Anna Dorothea Wagner, MD, of Vaudois University Hospital Center in Lausanne, Switzerland, and co-authors.
Grade 3/4 adverse events and serious adverse events occurred significantly more often with bevacizumab, but treatment-related deaths occurred less often, the investigators reported in the July issue of the Cochrane Database of Systematic Reviews.
"The overall patient benefit from adding bevacizumab to first- and second-line chemotherapy in metastatic breast cancer can at best be considered as modest," they wrote in conclusion. "It is dependent on the type of chemotherapy used and limited to a prolongation of [progression-free survival] and response rates."
"In contrast, bevacizumab has no significant impact on the patient-related secondary outcomes of overall survival or quality of life, which indicate a direct patient benefit," they added. "For this reason, the clinical value of bevacizumab for metastatic breast cancer remains controversial."
Multiple angiogenesis inhibitors have become available for cancer therapy in recent years, and many others have demonstrated activity in animal models of cancer. However, the benefits have tended to be heterogeneous and transient, both in preclinical and clinical settings, the authors wrote in their introduction.
Results of some pivotal studies of angiogenesis inhibitors have been frankly disappointing, leaving the clinical value of the drug class in question, they continued.
Wagner and colleagues sought to address some of the uncertainty by performing a systematic review of the safety and efficacy of therapies that target vascular endothelial growth factor (VEGF) in metastatic breast cancer.
Investigators reviewed published literature and data from several sources to identify randomized controlled trials and nonrandomized studies of VEGF-targeted therapies. The search had a starting point of 2000 for all information collected.
The search identified seven randomized trials and five ongoing trials. Four of the published trials focused on VEGF-targeted therapy for metastatic breast cancer, all involving bevacizumab.
The four trials included a total of 2,886 patients for comparison of chemotherapy with versus without bevacizumab. For first-line therapy, the analysis yielded a progression hazard ratio of 0.67 in favor of bevacizumab. Second-line therapy that included the angiogenesis inhibitor was associated with a progression hazard ratio of 0.85.
The data also showed higher objective response rates in first- and second-line therapy when bevacizumab was added to chemotherapy.
Quality-of-life data were limited to four trials (two published) and did not show a significant impact of anti-VEGF therapy.
Treatment with bevacizumab was associated with a 77 percent increase in the hazard for grade 3/4 adverse events and a 41 percent higher risk of serious adverse events. However, treatment-related deaths occurred significantly less often in bevacizumab-treated patients.