Yihebali Chi1, Yongqian Shu2, Yi Ba3, Yuxian Bai4, Baoli Qin5, Xiuwen Wang6, Jianping Xiong7, Nong Xu8, Helong Zhang9, Jianfeng Zhou10, Jianming Xu11, Ying Cheng12, Jifeng Feng13, Chunhong Hu14, Yigui Chen15, Zhendong Chen16, Jufeng Wang17, Chengxue Dang18, Jianhong Wang19, Yiye Wan20, Yong Tang21, Donglin Wang22, Jiang Liu23, Minhui Wu24, Yanhong Deng25, Xingwen Li26, Yongqiang Li27, Jian Dong28, Da Jiang29, Guisheng Li30, Qiong Wu31, Jin Li32, Yujuan Qi33, Yongkun Sun1, Jianqiang Cai34. 1. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. 2. Department of Medical Oncology, Jiangsu Province Hospital, Nanjing, People's Republic of China. 3. Department of Digestive Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, People's Republic of China. 4. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, People's Republic of China. 5. Department of Gastrointestinal Oncology, Liaoning Cancer Hospital & Institute, Shenyang, People's Republic of China. 6. Department of Chemotherapy, Qilu Hospital of Shandong University, Jinan, People's Republic of China. 7. Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China. 8. Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University, Hangzhou, People's Republic of China. 9. Department of Medical Oncology, Tangdu Hospital, Air Force Medical University, Xi'an, People's Republic of China. 10. Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, People's Republic of China. 11. Department of Gastrointestinal Oncology, 307 Hospital of PLA, Academy of Military Medical Sciences, Beijing, People's Republic of China. 12. Department of Medical Oncology, Jilin Cancer Hospital, Changchun, People's Republic of China. 13. Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing, People's Republic of China. 14. Department of Oncology, the Second Xiangya Hospital, Central South University, Changsha, People's Republic of China. 15. Department of Abdominal Oncology, Fujian Cancer Hospital, Fuzhou, People's Republic of China. 16. Department of Oncology, The Second Hospital of Anhui Medical University, Hefei, People's Republic of China. 17. Department of Oncology, Henan Cancer Hospital, Zhengzhou, People's Republic of China. 18. Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China. 19. Department of Medical Oncology, Nantong Tumor Hospital, Nantong, People's Republic of China. 20. Department of Medical Oncology, Jiangxi Cancer Hospital, Nanchang, People's Republic of China. 21. Department of Digestive Internal Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, People's Republic of China. 22. Department of Medical oncology, Chongqing Cancer Hospital, Chongqing, People's Republic of China. 23. Department of Medical Oncology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People's Republic of China. 24. Department of integrated Chinese and Western Medicine, Shaanxi Provincial Cancer Hospital, Xi'an, People's Republic of China. 25. Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China. 26. Department of Gastrointestinal Surgery, Gansu Provincial Cancer Hospital, Lanzhou, People's Republic of China. 27. Department of Medical Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China. 28. First Department of Medical Oncology, Yunnan Cancer Hospital, Kunming, People's Republic of China. 29. Department of Medical Oncology, Forth Hospital of Hebei Medical University, Hebei, People's Republic of China. 30. Department of Medical Oncology, Liuzhou Worker's Hospital, Liuzhou, People's Republic of China. 31. Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China. 32. Department of Medical Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China. 33. Department of Medical Oncology, Qinghai Provincial People's Hospital, Xining, People's Republic of China. 34. Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Abstract
BACKGROUND: Treatment options for refractory metastatic colorectal cancer (mCRC) were limited. Anlotinib is a novel multitarget tyrosine kinase inhibitor. ALTER0703 study was conducted to assess efficacy and safety of anlotinib for patients with refractory mCRC. MATERIALS AND METHODS: This was a multicenter, double-blinded, placebo-controlled, randomized phase III trial involving 33 hospitals in China. Patients had taken at least two lines of therapies were 2:1 randomized to receive oral anlotinib (12 mg/day; days 1-14; 21 days per cycle) or placebo, plus best supportive care. Randomization was stratified by previous VEGF-targeting treatments and time from diagnosis to metastases. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), and safety. RESULTS: A total of 419 patients (anlotinib: 282; placebo: 137) were treated from December 2014 to August 2016. The median PFS was improved in anlotinib group (4.1 months; 95% confidence interval [CI], 3.4-4.5) over placebo group (1.5 months; 95% CI, 1.4-1.5), with a hazard ratio (HR) of 0.34 (95% CI, 0.27-0.43; p < .0001). However, median OS was similar between two groups (8.6 months; 95% CI, 7.8-9.7 vs. 7.2 months; 95% CI, 6.2-8.8; HR, 1.02; p = .870). Improvements of ORR and DCR were observed in anlotinib over placebo. The most common grade ≥ 3 anlotinib related adverse events were hypertension (20.92%), increased γ-GT (7.09%), and hand-foot skin reaction (6.38%). CONCLUSION: Anlotinib was tolerated in Chinese patients with refractory mCRC. Although OS did not reach significant difference, anlotinib still provided clinical benefits by substantially prolonged PFS in these patients. IMPLICATIONS FOR PRACTICE: In this randomized clinical trial that included 419 patients with refractory metastatic colorectal cancer, substantial prolonged in progression-free survival was noted in patients who received anlotinib compared with those given placebo. Improvements on objective response rate and disease control rate was also observed in anlotinib group. However, overall survival was similar between the two groups. In a word, in third-line or above treatment of Chinese patients with refractory metastatic colorectal cancer, anlotinib provided clinical benefit by significantly prolonged progression-free survival.
BACKGROUND: Treatment options for refractory metastatic colorectal cancer (mCRC) were limited. Anlotinib is a novel multitarget tyrosine kinase inhibitor. ALTER0703 study was conducted to assess efficacy and safety of anlotinib for patients with refractory mCRC. MATERIALS AND METHODS: This was a multicenter, double-blinded, placebo-controlled, randomized phase III trial involving 33 hospitals in China. Patients had taken at least two lines of therapies were 2:1 randomized to receive oral anlotinib (12 mg/day; days 1-14; 21 days per cycle) or placebo, plus best supportive care. Randomization was stratified by previous VEGF-targeting treatments and time from diagnosis to metastases. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), and safety. RESULTS: A total of 419 patients (anlotinib: 282; placebo: 137) were treated from December 2014 to August 2016. The median PFS was improved in anlotinib group (4.1 months; 95% confidence interval [CI], 3.4-4.5) over placebo group (1.5 months; 95% CI, 1.4-1.5), with a hazard ratio (HR) of 0.34 (95% CI, 0.27-0.43; p < .0001). However, median OS was similar between two groups (8.6 months; 95% CI, 7.8-9.7 vs. 7.2 months; 95% CI, 6.2-8.8; HR, 1.02; p = .870). Improvements of ORR and DCR were observed in anlotinib over placebo. The most common grade ≥ 3 anlotinib related adverse events were hypertension (20.92%), increased γ-GT (7.09%), and hand-foot skin reaction (6.38%). CONCLUSION: Anlotinib was tolerated in Chinese patients with refractory mCRC. Although OS did not reach significant difference, anlotinib still provided clinical benefits by substantially prolonged PFS in these patients. IMPLICATIONS FOR PRACTICE: In this randomized clinical trial that included 419 patients with refractory metastatic colorectal cancer, substantial prolonged in progression-free survival was noted in patients who received anlotinib compared with those given placebo. Improvements on objective response rate and disease control rate was also observed in anlotinib group. However, overall survival was similar between the two groups. In a word, in third-line or above treatment of Chinese patients with refractory metastatic colorectal cancer, anlotinib provided clinical benefit by significantly prolonged progression-free survival.
Authors: Christopher T Ritchlin; Arthur Kavanaugh; Joseph F Merola; Georg Schett; Jose U Scher; Richard B Warren; Alice B Gottlieb; Deepak Assudani; Kathy Bedford-Rice; Jason Coarse; Barbara Ink; Iain B McInnes Journal: Lancet Date: 2020-02-08 Impact factor: 79.321
Authors: M Piccart; G N Hortobagyi; M Campone; K I Pritchard; F Lebrun; Y Ito; S Noguchi; A Perez; H S Rugo; I Deleu; H A Burris; L Provencher; P Neven; M Gnant; M Shtivelband; C Wu; J Fan; W Feng; T Taran; J Baselga Journal: Ann Oncol Date: 2014-09-17 Impact factor: 32.976
Authors: Richard S Finn; Baek-Yeol Ryoo; Philippe Merle; Masatoshi Kudo; Mohamed Bouattour; Ho Yeong Lim; Valeriy Breder; Julien Edeline; Yee Chao; Sadahisa Ogasawara; Thomas Yau; Marcelo Garrido; Stephen L Chan; Jennifer Knox; Bruno Daniele; Scot W Ebbinghaus; Erluo Chen; Abby B Siegel; Andrew X Zhu; Ann-Lii Cheng Journal: J Clin Oncol Date: 2019-12-02 Impact factor: 44.544
Authors: Roy S Herbst; Yan Sun; Wilfried E E Eberhardt; Paul Germonpré; Nagahiro Saijo; Caicun Zhou; Jie Wang; Longyun Li; Fairooz Kabbinavar; Yukito Ichinose; Shukui Qin; Li Zhang; Bonne Biesma; John V Heymach; Peter Langmuir; Sarah J Kennedy; Hiroomi Tada; Bruce E Johnson Journal: Lancet Oncol Date: 2010-07 Impact factor: 41.316