Anlotinib Monotherapy for Refractory Metastatic Colorectal Cancer: A Double-Blinded, Placebo-Controlled, Randomized Phase III Trial (ALTER0703)
Autor: | Guisheng Li, Qiong Wu, Jin Li, Xiuwen Wang, Yiye Wan, Ying Cheng, Jianping Xiong, Chunhong Hu, Jianqiang Cai, Yong-Qiang Li, Yong Tang, Helong Zhang, Jiang liu, Baoli Qin, Jifeng Feng, Jian Dong, Jianfeng Zhou, Yongqian Shu, Xingwen Li, Jianhong Wang, Yongkun Sun, Minhui Wu, Yigui Chen, Nong Xu, Zhendong Chen, Yuxian Bai, Jufeng Wang, Yanhong Deng, Da Jiang, Yi Ba, Chengxue Dang, Yujuan Qi, Jianming Xu, Donglin Wang, Yihebali Chi |
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Rok vydání: | 2021 |
Předmět: |
Cancer Research
medicine.medical_specialty Indoles Randomization Placebo law.invention 03 medical and health sciences 0302 clinical medicine Double-Blind Method Randomized controlled trial Refractory law Internal medicine Gastrointestinal Cancer medicine Clinical endpoint Humans 030212 general & internal medicine Progression-free survival Adverse effect business.industry Hazard ratio Oncology 030220 oncology & carcinogenesis Quality of Life Quinolines Colorectal Neoplasms business |
Zdroj: | Oncologist |
ISSN: | 1549-490X 1083-7159 |
Popis: | 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. |
Databáze: | OpenAIRE |
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