title: Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study.
abstract: To assess the efficacy and safety of fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, in metastatic colorectal cancer (mCRC) patients.
  
  
  
  A phase Ib open-label study and phase II randomized, placebo-controlled trial compared the efficacy of fruquintinib plus best supportive care (BSC) with placebo plus BSC in mCRC patients with ≥2 lines of prior therapies. The primary endpoint was progression-free survival (PFS).
  
  
  
  In the phase Ib study, 42 patients took fruquintinib 5 mg for 3 weeks on/1 week off. The median PFS was 5.80 months, and the median overall survival (OS) was 8.88 months. In the phase II study, 71 patients were randomized (47 to fruquintinib, 24 to placebo). PFS was significantly improved with fruquintinib plus BSC (4.73 months; 95% confidence interval [CI] 2.86-5.59) versus placebo plus BSC (0.99 months; 95% CI 0.95-1.58); (hazard ratio [HR] 0.30; 95% CI 0.15-0.59; P < 0.001). The median OS was 7.72 versus 5.52 months (HR 0.71; 95% CI 0.38-1.34). The most common grade 3-4 adverse events were hypertension and hand-foot skin reaction.
  
  
  
  Fruquintinib showed a significant PFS benefit of 3.7 months in patients with treatment-refractory mCRC. The safety profile was consistent with that of VEGFR tyrosine kinase inhibitors. A randomized phase III confirmatory study in mCRC is underway.
  
  
  
  NCT01975077 and NCT02196688.
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, 200032, China. tianyoulijin@163.com.|Department of Oncology, Tongji University Shanghai East Hospital, No. 150 Jimo Road, Pudong District, Shanghai, 200120, China. tianyoulijin@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Yuxian
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Medical Oncology, 307th Hospital of PLA, Academy of Military Medical Sciences, Beijing, 100071, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Fudan University Zhongshan Hospital, Shanghai Medical College, Shanghai, 200032, China.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Beijing Cancer Hospital, Beijing, 100142, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Medical Oncology, Shanghai First People's Hospital, Shanghai, 200090, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, 200032, China.
authors.forename: Junning
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Hutchison MediPharma Ltd, Shanghai, 201203, China.
authors.forename: Songhua
authors.initials: S
authors.lastname: Fan
authors.affiliation: Hutchison MediPharma Ltd, Shanghai, 201203, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Hua
authors.affiliation: Hutchison MediPharma Ltd, Shanghai, 201203, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Su
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary*; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001572:Benzofurans / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000074322:Antineoplastic Agents, Immunological; D001572:Benzofurans; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C000591844:HMPL-013; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Fruquintinib; Metastatic colorectal cancer; Progression-free survival; VEGFR