Minoru Miyashita1, Masaya Hattori2, Toshimi Takano3, Tatsuya Toyama4, Hiroji Iwata2. 1. Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. atihsayim8m8@med.tohoku.ac.jp. 2. Department of Breast Oncology, Aichi Cancer Center, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. 3. Department of Medical Oncology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan. 4. Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
Abstract
BACKGROUND: The combination of bevacizumab and chemotherapy has greatly improved progression-free survival (PFS) and objective response rate (ORR) in HER2-negative metastatic breast cancer in many pivotal trials. However, risk-benefit balance related to bevacizumab addition could not be confirmed because of a lack of overall survival (OS) improvement. Therefore, we conducted a meta-analysis to evaluate multiple endpoints pertaining to bevacizumab use in metastatic breast cancer (MBC) treatment. METHODS: We searched PubMed and Cochrane Library databases and included seven studies in our meta-analysis in which bevacizumab combined with chemotherapy was compared with chemotherapy alone in MBC. RESULTS: Compared to the chemotherapy-alone group, the combination treatment group had significantly improved PFS [hazard ratio (HR): 0.72, 95% CI 0.67-0.77, P < 0.00001]. Furthermore, bevacizumab addition did not significantly improve OS (HR: 0.95, 95% CI 0.87-1.03, P = 0.22). The ORRs in the combination treatment and chemotherapy-alone groups were 42% and 32%, respectively (HR: 1.47, 95% CI 1.26-1.71, P < 0.00001). Bevacizumab addition significantly increased the incidence of therapy discontinuation due to toxicity and toxicity of grade 3 or higher (HR: 1.43, 95% CI 1.06-1.93, P = 0.02, HR: 1.43; 95% CI 1.25-1.64, P < 0.00001, respectively). A qualitative systematic review of two randomized controlled trials indicated no significant differences in quality of life from baseline between the two groups. CONCLUSIONS: Compared to chemotherapy alone, bevacizumab combined with chemotherapy significantly improved PFS in the HER2-negative MBC patients. However, the lack of a significant OS difference remained.
BACKGROUND: The combination of bevacizumab and chemotherapy has greatly improved progression-free survival (PFS) and objective response rate (ORR) in HER2-negative metastatic breast cancer in many pivotal trials. However, risk-benefit balance related to bevacizumab addition could not be confirmed because of a lack of overall survival (OS) improvement. Therefore, we conducted a meta-analysis to evaluate multiple endpoints pertaining to bevacizumab use in metastatic breast cancer (MBC) treatment. METHODS: We searched PubMed and Cochrane Library databases and included seven studies in our meta-analysis in which bevacizumab combined with chemotherapy was compared with chemotherapy alone in MBC. RESULTS: Compared to the chemotherapy-alone group, the combination treatment group had significantly improved PFS [hazard ratio (HR): 0.72, 95% CI 0.67-0.77, P < 0.00001]. Furthermore, bevacizumab addition did not significantly improve OS (HR: 0.95, 95% CI 0.87-1.03, P = 0.22). The ORRs in the combination treatment and chemotherapy-alone groups were 42% and 32%, respectively (HR: 1.47, 95% CI 1.26-1.71, P < 0.00001). Bevacizumab addition significantly increased the incidence of therapy discontinuation due to toxicity and toxicity of grade 3 or higher (HR: 1.43, 95% CI 1.06-1.93, P = 0.02, HR: 1.43; 95% CI 1.25-1.64, P < 0.00001, respectively). A qualitative systematic review of two randomized controlled trials indicated no significant differences in quality of life from baseline between the two groups. CONCLUSIONS: Compared to chemotherapy alone, bevacizumab combined with chemotherapy significantly improved PFS in the HER2-negative MBC patients. However, the lack of a significant OS difference remained.
Entities:
Keywords:
Bevacizumab; Meta-analysis; Metastatic breast cancer; Systematic review