Shun Lu1, Gongyan Chen2, Yuping Sun3, Sanyuan Sun4, Jianhua Chang5, Yu Yao6, Zhendong Chen7, Feng Ye8, Junguo Lu9, Jianhua Shi10, Jianxing He11, Xiaoqing Liu12, Yiping Zhang13, Zhihua Liu14, Jian Fang15, Ying Cheng16, Chunhong Hu17, Weidong Mao18, Yanping Hu19, Youling Gong20, Li Shan21, Zhixiong Yang22, Yong Song23, Wei Li24, Chong Bai25, Buhai Wang26, Rui Ma27, Zhendong Zheng28, Mingfang Liu29, Zhijun Jie30, Lejie Cao31, Wangjun Liao32, Hongming Pan33, Dongning Huang34, Yuan Chen35, Jinji Yang36, Shukui Qin37, Shenglin Ma38, Li Liang39, Zhe Liu40, Jianying Zhou41, Min Tao42, Yijiang Huang43, Feng Qiu44, Yunchao Huang45, Sha Guan46, Mengye Peng46, Weiguo Su46. 1. Shanghai Lung Cancer Center, Shanghai Chest Hospital, Jiao Tong University, China. Electronic address: shunlu@sjtu.edu.cn. 2. Harbin Medical University Cancer Hospital, China. 3. Jinan Central Hospital, China. 4. XuZhou Central Hospital, China. 5. Fudan University Shanghai Cancer Center, China. 6. The First Affiliated Hospital of Xi'an Jiaotong University, China. 7. The Second Hospital of Anhui Medical University, China. 8. Xiamen Key Laboratory of Antitumor Drug Transformation Research, The First Affiliated Hospital of Xiamen University, China. 9. Nantong Tumor Hospital, China. 10. Linyi Cancer Hospital, China. 11. The First Affiliated Hospital of Guangzhou Medical University, China. 12. The Fifth Medical Center, General Hospital of the People's Liberation Army, China. 13. Zhejiang Cancer Hospital, China. 14. Jiangxi Cancer Hospital, China. 15. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, China. 16. Jilin Cancer Hospital, China. 17. The Second Xiangya Hospital of Central South University, China. 18. Jiangyin People's Hospital, China. 19. Hubei Cancer Hospital, China. 20. West China Hospital of Sichuan University, China. 21. Xinjiang Cancer Hospital, China. 22. Affiliated Hospital of Guangdong Medical University, China. 23. Jinling Hospital, Nanjing University School of Medicine, China. 24. The First Hospital of Jilin University, China. 25. Shanghai Changhai Hospital, China. 26. Northern Jiangsu People's Hospital, China. 27. Liaoning Cancer Hospital, China. 28. General Hospital of Northern Theater Command, China. 29. General Hospital of Ningxia Medical University, China. 30. The Fifth People's Hospital of Shanghai, China. 31. The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, China. 32. Nanfang Hospital of Southern Medical University, China. 33. Sir Run Run Shaw Hospital Affiliated with School of Medicine, Zhejiang University, China. 34. The Fourth Affiliated Hospital of Guangxi Medical University, China. 35. Tongji Hospital, Tongji Medical College of Hust, China. 36. Guandong Provincial People's Hospital, China. 37. People's Liberation Army Cancer Center of Nanjing Jinling Hospital, China. 38. Hangzhou First People's Hospital, China. 39. Peking University Third Hospital, China. 40. Beijing Chest Hospital, Capital Medical University, China. 41. The First Affiliated Hospital, Zhejiang University, China. 42. The First Affiliated Hospital of Soochow University, China. 43. Hainan General Hospital, China. 44. The First Affiliated Hospital of Nanchang University, China. 45. Yunnan Cancer Hospital, China. 46. Hutchison MediPharma, Shanghai, China.
Abstract
OBJECTIVES: Fruquintinib is an orally active kinase inhibitor that selectively targets the vascular endothelial growth factor (VEGF) receptor. A Phase II trial has demonstrated a significant benefit in progression-free survival (PFS) for fruquintinib-treated patients with locally advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC) who have progressed after second-line chemotherapy. This Phase III trial is a randomized, double-blind, multicenter trial to confirm fruquintinib's efficacy in the same patient population. MATERIALS AND METHODS: From December 2015 to February 2018, 730 patients were screened, of whom 527 were enrolled into the study. Participants were randomized 2:1 to receive fruquintinib (n = 354) or placebo (n = 173) once daily for 3 weeks on-treatment, and 1 week off-treatment. Patients were stratified according to epidermal growth factor receptor mutation status and prior use of VEGF inhibitors. Primary endpoint was overall survival (OS). RESULTS: Median OS was 8.9 months for the fruquintinib group and 10.4 months for placebo group (hazard ratio [HR] 1.02; 95 % confidence interval [CI], 0.82-1.28; P = 0.841), with median PFS of 3.7 months and 1.0 months, respectively (HR 0.34; 95 % CI, 0.28-0.43; P < 0.001). Objective response rate and disease control rate were 13.8 % and 66.7 % for fruquintinib, and 0.6 % and 24.9 % for placebo, respectively (P < 0.001). Hypertension was the most frequent treatment-emergent adverse event (≥grade 3) observed in fruquintinib-treated patients (21.0 %). Post hoc analysis revealed that fruquintinib prolonged the median OS for patients who did not receive subsequent antitumor therapy: 7.0 months versus 5.1 months for placebo (HR 0.65; 95 % CI, 0.46-0.91; P = 0.012). Patients receiving fruquintinib also reported improvements in quality of life for most functional scales measured by EORTC QLQ-C30 and LC13 questionnaires. CONCLUSION: Although the study did not meet its primary endpoint, fruquintinib could be effective in combination with other agents for the treatment of patients with NSCLC who have failed second-line chemotherapy.
OBJECTIVES: Fruquintinib is an orally active kinase inhibitor that selectively targets the vascular endothelial growth factor (VEGF) receptor. A Phase II trial has demonstrated a significant benefit in progression-free survival (PFS) for fruquintinib-treated patients with locally advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC) who have progressed after second-line chemotherapy. This Phase III trial is a randomized, double-blind, multicenter trial to confirm fruquintinib's efficacy in the same patient population. MATERIALS AND METHODS: From December 2015 to February 2018, 730 patients were screened, of whom 527 were enrolled into the study. Participants were randomized 2:1 to receive fruquintinib (n = 354) or placebo (n = 173) once daily for 3 weeks on-treatment, and 1 week off-treatment. Patients were stratified according to epidermal growth factor receptor mutation status and prior use of VEGF inhibitors. Primary endpoint was overall survival (OS). RESULTS: Median OS was 8.9 months for the fruquintinib group and 10.4 months for placebo group (hazard ratio [HR] 1.02; 95 % confidence interval [CI], 0.82-1.28; P = 0.841), with median PFS of 3.7 months and 1.0 months, respectively (HR 0.34; 95 % CI, 0.28-0.43; P < 0.001). Objective response rate and disease control rate were 13.8 % and 66.7 % for fruquintinib, and 0.6 % and 24.9 % for placebo, respectively (P < 0.001). Hypertension was the most frequent treatment-emergent adverse event (≥grade 3) observed in fruquintinib-treated patients (21.0 %). Post hoc analysis revealed that fruquintinib prolonged the median OS for patients who did not receive subsequent antitumor therapy: 7.0 months versus 5.1 months for placebo (HR 0.65; 95 % CI, 0.46-0.91; P = 0.012). Patients receiving fruquintinib also reported improvements in quality of life for most functional scales measured by EORTC QLQ-C30 and LC13 questionnaires. CONCLUSION: Although the study did not meet its primary endpoint, fruquintinib could be effective in combination with other agents for the treatment of patients with NSCLC who have failed second-line chemotherapy.
Authors: Mohammad M Al-Sanea; Ghada H Al-Ansary; Zainab M Elsayed; Raed M Maklad; Eslam B Elkaeed; Mohamed A Abdelgawad; Syed Nasir Abbas Bukhari; Marwa M Abdel-Aziz; Howayda Suliman; Wagdy M Eldehna Journal: J Enzyme Inhib Med Chem Date: 2021-12 Impact factor: 5.051
Authors: Shun Lu; Jian-Ying Zhou; Xiao-Min Niu; Jian-Ya Zhou; Hong Jian; Hong-Yan Yin; Sha Guan; Lin-Fang Wang; Ke Li; James He; Wei-Guo Su Journal: Transl Lung Cancer Res Date: 2021-02