B Xu1, T Sun2, Q Zhang3, P Zhang4, Z Yuan5, Z Jiang6, X Wang7, S Cui8, Y Teng9, X-C Hu10, J Yang11, H Pan12, Z Tong13, H Li27, Q Yao15, Y Wang16, Y Yin17, P Sun18, H Zheng19, J Cheng20, J Lu21, B Zhang22, C Geng23, J Liu24, K Shen25, S Yu26, H Li27, L Tang28, R Qiu28. 1. Department of Medical Oncology, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; State Key Laboratory of Molecular Oncology, National Cancer Centre/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: bhxu@hotmail.com. 2. Department of Internal Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China. 3. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China. 4. Department of Medical Oncology, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 5. Department of Medical Oncology, Sun Yat-sen University Cancer Centre, Guangzhou, China. 6. Department of Breast Cancer, The Fifth Medical Cent, Chinese PLA General Hospital, Beijing, China. 7. Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China. 8. Breast Cancer Centre, Henan Cancer Hospital, Zhengzhou, China. 9. Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China. 10. Department of Medical Oncology, Fudan University Cancer Center, Shanghai, China. 11. Department of Medical Oncology, The PLA General Hospital, Beijing, China. 12. Department of Medical Oncology, Sir Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. 13. Department of Breast Oncology, Tianjin Medical University Cancer Hospital, Tianjin, China. 14. Department of Breast Oncology, Peking University Cancer Hospital, Beijing, China. 15. Department of Medical Oncology, Nankai University Tianjing People's Hospital, Tianjing, China. 16. Breast Cancer Center, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China. 17. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 18. Department of Oncology, Qingdao University Yantai Yuhuangding Hospital, Yantai, China. 19. Department of Medical Oncology, Sichuan University West China Hospital, Chengdu, China. 20. Department of Oncology, Tongji Medical College Wuhan Union Hospital, Wuhan, China. 21. Department of Breast Surgery, Shanghai Jiaotong University Renji Hospital, Shanghai, China. 22. Department of Medical Oncology, Nantong Tumor Hospital, Nantong, China. 23. Department of Breast Oncology, Hebei Medical University Tumor Hospital, Shijiazhuang, China. 24. Department of Medical Oncology, Fujian Medical University Cancer Hospital, Fuzhou, China. 25. Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 26. Cancer Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. 27. Department of Breast Surgery, Sichuan Cancer Hospital, Chengdu, China. 28. Department of Research and Development, Beijing Biostar Technologies, Beijing, China.
Abstract
BACKGROUND: Primary analysis of the phase III trial BG01-1323L demonstrated that utidelone plus capecitabine significantly improved progression-free survival (PFS) and overall response rate (ORR) versus capecitabine alone in heavily-pretreated patients with metastatic breast cancer (MBC). Here, we report the final overall survival (OS) analysis and updates of other endpoints. PATIENTS AND METHODS: In total, 405 patients were randomised 2:1 to receive utidelone (30 mg/m2 IV daily, days 1-5, over 90 min) plus capecitabine (1000 mg/m2 orally b.i.d., days 1-14) or capecitabine alone (1250 mg/m2 orally b.i.d., days 1-14) every 21 days. The secondary endpoint, OS, was estimated using the Kaplan-Meier product-limit approach at a two-sided alpha level of 0.05 after the prespecified 310 death events had been reached. Exploratory analyses of the primary endpoint, PFS, and the secondary endpoint, ORR, were also done. Safety was analysed in patients who had at least one dose of study drug. RESULTS: At the final OS analysis, the median duration of follow-up was 19.6 months in the utidelone plus capecitabine group and 15.4 months in the capecitabine alone group. In the intention-to-treat population, 313 deaths had occurred at data cut-off, 203 of 270 patients in the combination group and 110 of 135 in the monotherapy group. Median OS in the combination group was 19.8 months compared with 16.0 months in the monotherapy group [hazard ratio (HR) = 0.75, 95% confidence intervals (CI) 0.59-0.94, P = 0.0142]. The updated analysis of PFS and ORR showed that the combination therapy remained superior to monotherapy. Safety results were similar to those previously reported with respect to incidence, severity and specificity. No late-emerging toxicities or new safety concerns occurred. CONCLUSIONS: For heavily-pretreated, anthracycline- and taxane-resistant MBC patients, utidelone plus capecitabine significantly improved OS versus capecitabine alone. These results support the use of utidelone plus capecitabine as a novel therapeutic regimen for patients with MBC.
BACKGROUND: Primary analysis of the phase III trial BG01-1323L demonstrated that utidelone plus capecitabine significantly improved progression-free survival (PFS) and overall response rate (ORR) versus capecitabine alone in heavily-pretreated patients with metastatic breast cancer (MBC). Here, we report the final overall survival (OS) analysis and updates of other endpoints. PATIENTS AND METHODS: In total, 405 patients were randomised 2:1 to receive utidelone (30 mg/m2 IV daily, days 1-5, over 90 min) plus capecitabine (1000 mg/m2 orally b.i.d., days 1-14) or capecitabine alone (1250 mg/m2 orally b.i.d., days 1-14) every 21 days. The secondary endpoint, OS, was estimated using the Kaplan-Meier product-limit approach at a two-sided alpha level of 0.05 after the prespecified 310 death events had been reached. Exploratory analyses of the primary endpoint, PFS, and the secondary endpoint, ORR, were also done. Safety was analysed in patients who had at least one dose of study drug. RESULTS: At the final OS analysis, the median duration of follow-up was 19.6 months in the utidelone plus capecitabine group and 15.4 months in the capecitabine alone group. In the intention-to-treat population, 313 deaths had occurred at data cut-off, 203 of 270 patients in the combination group and 110 of 135 in the monotherapy group. Median OS in the combination group was 19.8 months compared with 16.0 months in the monotherapy group [hazard ratio (HR) = 0.75, 95% confidence intervals (CI) 0.59-0.94, P = 0.0142]. The updated analysis of PFS and ORR showed that the combination therapy remained superior to monotherapy. Safety results were similar to those previously reported with respect to incidence, severity and specificity. No late-emerging toxicities or new safety concerns occurred. CONCLUSIONS: For heavily-pretreated, anthracycline- and taxane-resistant MBC patients, utidelone plus capecitabine significantly improved OS versus capecitabine alone. These results support the use of utidelone plus capecitabine as a novel therapeutic regimen for patients with MBC.
Authors: Anna Linehan; Orla Fitzpatrick; Darren Cowzer; Maeve A Hennessy; Zac L Coyne; Amy Nolan; Maeve Clarke; Roisin Ni Dhonaill; Bryan T Hennessy; Patrick G Morris; Liam Grogan; Oscar Breathnach Journal: Ir J Med Sci Date: 2021-10-25 Impact factor: 2.089