A randomized parallel controlled phase II trial of recombinant human endostatin added to neoadjuvant chemotherapy for stage III breast cancer

Abstract Background To explore the potential advantage of preoperative antiangiogenosis 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 docetaxel, epirubicin and cyclophosphamide (TEC) or to EN+TEC, followed by surgery. The primary endpoint was objective response rate (ORR). Secondary endpoints included pathological 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%). Median follow-up was 54 months, and revealed a significantly higher RFS with EN+TEC (median: 67.3 months, 95% CI 61.0-73.7), compared to TEC (median: 55.0 months, 95% CI 48.3-61.7), p=0.014. EN+TEC also significantly improved OS (74.2 months, 95% CI 68.9-79.6), compared with TEC (59.1 months, 95% CI 52.0-66.1), 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 (HR: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. Trial registration Clinical trials.gov identifier: NCT01907529