Xiangmei Zhang1, Zhenzhen Zhang2, Miao Cao3, Beichen Liu4, Motomi Mori5, Shiuh-Wen Luoh6, Raymond Bergan7, Yueping Liu8, Yunjiang Liu9. 1. Research Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 2. OHSU-PSU School of Public Health, Oregon Health and Science University, Portland, OR. 3. Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 4. Department of Hematology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 5. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN. 6. Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR. 7. Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR. 8. Department of Pathology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 9. Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. Electronic address: lyj818326@outlook.com.
Abstract
BACKGROUND: To explore the potential advantage of preoperative anti-angiogenosis therapy, we implemented a study to evaluate the efficacy of recombinant human endostatin (EN) in combination with neoadjuvant chemotherapy in the treatment of stage III breast cancer. PATIENTS AND METHODS: Eighty-seven patients were randomized to neoadjuvant TEC (docetaxel, epirubicin, and cyclophosphamide) or to EN+TEC, followed by surgery. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), relapse-free survival (RFS), overall survival (OS), and safety. RESULTS: Patients receiving EN+TEC achieved significantly higher ORR (81.82%; 36/44) compared with those receiving TEC (58.14%; 25/43; P=0.016). There was a non-significant trend of increased pCR with EN treatment (15.91% vs. 6.98%). The median follow-up was 54 months and revealed a significantly higher RFS with EN+TEC (median, 67.3 months; 95% confidence interval [CI], 61.0-73.7 months), compared with TEC (median, 55.0 months; 95% CI, 48.3-61.7 months; P =0.014). EN+TEC also significantly improved OS (74.2 months; 95% CI, 68.9-79.6 months), compared with TEC (59.1 months; 95% CI, 52.0-66.1 months; P =0 .006). The 3- and 5-year OS rates are estimated to be 88.5% and 82.8% with EN+TEC and 76.7% and 54.4% with TEC, respectively. Cox proportional regression analyses showed that EN+TEC was associated with improved OS (hazard ratio, 0.377; 95% CI, 0.418-0.959; P =0 .041). There was no significant difference in adverse events between EN+TEC and TEC. CONCLUSION: The combination of EN+TECneoadjuvant chemotherapy significantly improved the ORR and OS, suggesting a benefit of adding anti-angiogenesis to standard chemotherapy in the treatment of locally advanced breast cancer.
RCT Entities:
BACKGROUND: To explore the potential advantage of preoperative anti-angiogenosis therapy, we implemented a study to evaluate the efficacy of recombinant humanendostatin (EN) in combination with neoadjuvant chemotherapy in the treatment of stage III breast cancer. PATIENTS AND METHODS: Eighty-seven patients were randomized to neoadjuvant TEC (docetaxel, epirubicin, and cyclophosphamide) or to EN+TEC, followed by surgery. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), relapse-free survival (RFS), overall survival (OS), and safety. RESULTS:Patients receiving EN+TEC achieved significantly higher ORR (81.82%; 36/44) compared with those receiving TEC (58.14%; 25/43; P=0.016). There was a non-significant trend of increased pCR with EN treatment (15.91% vs. 6.98%). The median follow-up was 54 months and revealed a significantly higher RFS with EN+TEC (median, 67.3 months; 95% confidence interval [CI], 61.0-73.7 months), compared with TEC (median, 55.0 months; 95% CI, 48.3-61.7 months; P =0.014). EN+TEC also significantly improved OS (74.2 months; 95% CI, 68.9-79.6 months), compared with TEC (59.1 months; 95% CI, 52.0-66.1 months; P =0 .006). The 3- and 5-year OS rates are estimated to be 88.5% and 82.8% with EN+TEC and 76.7% and 54.4% with TEC, respectively. Cox proportional regression analyses showed that EN+TEC was associated with improved OS (hazard ratio, 0.377; 95% CI, 0.418-0.959; P =0 .041). There was no significant difference in adverse events between EN+TEC and TEC. CONCLUSION: The combination of EN+TEC neoadjuvant chemotherapy significantly improved the ORR and OS, suggesting a benefit of adding anti-angiogenesis to standard chemotherapy in the treatment of locally advanced breast cancer.