Safety Profile and Adverse Events of Special Interest for Fruquintinib in Chinese Patients with Previously Treated Metastatic Colorectal Cancer: Analysis of the Phase 3 FRESCO Trial

被引：24

作者：

Li, Jin ^{[1
]}

Guo, Weijian ^{[2
]}

Bai, Yuxian ^{[3
]}

Deng, Yanhong ^{[4
]}

Yang, Lei ^{[5
]}

Chen, Zhendong ^{[6
]}

Zhong, Haijun ^{[7
]}

Xu, Ruihua ^{[8
]}

Pan, Hongming ^{[9
]}

Shu, Yongqian ^{[10
]}

Yuan, Ying ^{[11
]}

Zhou, Jianfeng ^{[12
]}

Xu, Nong ^{[13
]}

Liu, Tianshu ^{[14
]}

Ma, Dong ^{[15
]}

Wu, Changping ^{[16
]}

Cheng, Ying ^{[17
]}

Xu, Jianming ^{[18
]}

Chen, Donghui ^{[19
]}

Li, Wei ^{[20
]}

Sun, Sanyuan ^{[21
]}

Yu, Zhuang ^{[22
]}

Cao, Peiguo ^{[23
]}

Shen, Lin ^{[24
]}

Chen, Haihui ^{[25
]}

Wang, Shubin ^{[26
]}

Wang, Hongbing ^{[27
]}

Fan, Songhua ^{[28
]}

Guo, Xiaojun ^{[28
]}

Wang, Ning ^{[29
]}

Han, Rubing ^{[29
]}

Zhang, Bin ^{[29
]}

Qin, Shukui ^{[30
]}

机构：

[1] Tongji Univ, East Hosp, Dept Med Oncol, Shanghai, Peoples R China

[2] Fudan Univ, Shanghai Canc Ctr, Shanghai Med Coll, Dept Med Oncol, Shanghai, Peoples R China

[3] Harbin Med Univ, Canc Hosp, Dept Med Oncol, Harbin, Peoples R China

[4] Sun Yat Sen Univ, Hosp 6, Dept Med Oncol, Guangzhou, Peoples R China

[5] Nantong Canc Hosp, Dept Med Oncol, Nantong, Peoples R China

[6] Anhui Med Univ, Hosp 2, Dept Med Oncol, Hefei, Peoples R China

[7] Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou, Peoples R China

[8] Sun Yat Sen Univ, Canc Ctr, Dept Med Oncol, Guangzhou, Peoples R China

[9] Sir Run Run Shaw Hosp, Dept Med Oncol, Hangzhou, Peoples R China

[10] Jiangsu Prov Hosp, Dept Med Oncol, Nanjing, Peoples R China

[11] Zhejiang Univ, Affiliated Hosp 2, Dept Med Oncol, Hangzhou, Peoples R China

[12] Peking Union Med Coll Hosp, Dept Oncol, Beijing, Peoples R China

[13] Zhejiang Univ, Affiliated Hosp 1, Coll Med, Dept Med Oncol, Hangzhou, Peoples R China

[14] Fudan Univ, Zhongshan Hosp, Dept Med Oncol, Shanghai, Peoples R China

[15] Guangdong Prov Peoples Hosp, Dept Med Oncol, Guangzhou, Peoples R China

[16] First Peoples Hosp Changzhou, Dept Med Oncol, Changzhou, Jiangsu, Peoples R China

[17] Jilin Prov Canc Hosp, Dept Med Oncol, Changchun, Peoples R China

[18] Peoples Liberat Army Gen Hosp, Med Ctr Chinese 5, Dept Med Oncol, Beijing, Peoples R China

[19] Shanghai Jiao Tong Univ Affiliated Peoples Hosp 1, Dept Med Oncol, Shanghai, Peoples R China

[20] First Hosp Jilin Univ, Dept Med Oncol, Changchun, Peoples R China

[21] Xuzhou Cent Hosp, Dept Med Oncol, Xuzhou, Jiangsu, Peoples R China

[22] Qingdao Univ, Med Coll, Affiliated Hosp, Dept Med Oncol, Qingdao, Peoples R China

[23] Cent South Univ, Xiangya Hosp 3, Xiangya Hosp, Dept Med Oncol, Changsha, Peoples R China

[24] Peking Univ Canc Hosp & Inst, Minist Educ, Dept Gastrointestinal Oncol, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China

[25] Liuzhou Workers Hosp, Dept Med Oncol, Liuzhou, Peoples R China

[26] Beijing Univ, ShenZhen Hosp, Dept Med Oncol, Shenzhen, Peoples R China

[27] Xuzhou Med Coll, Affiliated Hosp, Dept Med Oncol, Xuzhou, Jiangsu, Peoples R China

[28] Hutchison MediPharma Ltd, Shanghai, Peoples R China

[29] Lilly China, Drug Dev & Med Affairs Ctr, Shanghai, Peoples R China

[30] Jinling Hosp, Canc Ctr, Nanjing, Peoples R China

来源：

ADVANCES IN THERAPY | 2020年 / 37卷 / 11期

关键词：

Adverse events of special interest; Chinese patients; FRESCO trial; Fruquintinib; Metastatic colorectal cancer; Safety profile; THERAPY; SUNITINIB; PLACEBO; MECHANISMS; INHIBITOR; SURVIVAL; GROWTH;

D O I：

10.1007/s12325-020-01477-w

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Introduction In FRESCO (Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients) trial, fruquintinib demonstrated a statistically significant and clinically meaningful overall survival benefit in Chinese patients with metastatic colorectal cancer (mCRC). However, its safety profile, including adverse events of special interest (AESIs) and treatment-emergent adverse events (TEAEs) by age, sex, and body mass index (BMI), is not well known. The present analysis evaluated the safety profile and AESIs for fruquintinib in the FRESCO trial. Methods In FRESCO, eligible Chinese patients were randomized (2:1) to receive fruquintinib (5 mg once daily for 3 weeks, followed by 1 week off in 28-day cycles) or placebo plus best supportive care. Treatment-related AESIs and time to first occurrence of AESIs were summarized. Treatment-related TEAEs by age, sex, and BMI were also summarized. Results A total of 266 patients (95.7%) in the fruquintinib group and 97 (70.8%) in the placebo group had at least one treatment-related TEAE; the mean relative dose intensity was 92% and 98%, respectively. In the fruquintinib group, the most common (in > 40% of patients) treatment-related AESIs were hypertension (55.4%), palmar-plantar erythrodysesthesia syndrome [known as hand-foot skin reaction (HFSR)] (49.3%), and proteinuria (42.1%). The most common treatment-related grade >= 3 AESIs (>= 3% of patients) were hypertension (21.2%), HFSR (10.8%), and proteinuria (3.2%); the median time to onset of these events was 10, 21, and 20 days, respectively. Subgroup analysis by age, sex, and BMI revealed that the frequencies of treatment-related TEAEs were similar across all subgroups, and were consistent with the overall safety profile of fruquintinib. Conclusions The most common treatment-related grade >= 3 AEs were hypertension, HFSR, and proteinuria. The treatment-related TEAE profile of fruquintinib in Chinese patents with mCRC was comparable among different subgroups and consistent with that reported in the overall population.

引用

页码：4585 / 4598

页数：14

共 33 条

[1]

[Anonymous], 2007, Food, nutrition, physical activity, and the prevention of cancer: A global perspective

[2]

[Anonymous], 2019, ELUNATE FRUQUINTINIB

[3] Global patterns and trends in colorectal cancer incidence and mortality [J].

Arnold, Melina ;

Sierra, Monica S. ;

Laversanne, Mathieu ;

Soerjomataram, Isabelle ;

Jemal, Ahmedin ;

Bray, Freddie .

GUT, 2017, 66 (04) :683-691

[4] Clinical outcomes of Chinese patients with metastatic colorectal cancer receiving first-line bevacizumab-containing treatment [J].

Bai, Long ;

Zhang, Dong-sheng ;

Wu, Wen-jing ;

Ren, Chao ;

Wang, De-shen ;

Wang, Feng ;

Qiu, Miao-zhen ;

Xu, Rui-hua .

MEDICAL ONCOLOGY, 2015, 32 (02)

[5] A Phase I study of safety and pharmacokinetics of fruquintinib, a novel selective inhibitor of vascular endothelial growth factor receptor-1,-2, and-3 tyrosine kinases in Chinese patients with advanced solid tumors [J].

Cao, Junning ;

Zhang, Jian ;

Peng, Wei ;

Chen, Zhiyu ;

Fan, Songhua ;

Su, Weiguo ;

Li, Ke ;

Li, Jin .

CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2016, 78 (02) :259-269

[6] Molecular mechanisms and clinical applications of angiogenesis [J].

Carmeliet, Peter ;

Jain, Rakesh K. .

NATURE, 2011, 473 (7347) :298-307

[7] Cancer Statistics in China, 2015 [J].

Chen, Wanqing ;

Zheng, Rongshou ;

Baade, Peter D. ;

Zhang, Siwei ;

Zeng, Hongmei ;

Bray, Freddie ;

Jemal, Ahmedin ;

Yu, Xue Qin ;

He, Jie .

CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132

[8] Pharmacogenomics of intrinsic and acquired pharmacoresistance in colorectal cancer: Toward targeted personalized therapy [J].

De Mattia, Elena ;

Cecchin, Erika ;

Toffoli, Giuseppe .

DRUG RESISTANCE UPDATES, 2015, 20 :39-70

[9] Toxicities of Targeted Therapy and Their Management in Kidney Cancer [J].

Di Lorenzo, Giuseppe ;

Porta, Camillo ;

Bellmunt, Joaquim ;

Sternberg, Cora ;

Kirkali, Ziya ;

Staehler, Michael ;

Joniau, Steven ;

Montorsi, Francesco ;

Buonerba, Carlo .

EUROPEAN UROLOGY, 2011, 59 (04) :526-540

[10] Sorafenib in advanced clear-cell renal-cell carcinoma [J].

Escudier, Bernard ;

Eisen, Tim ;

Stadler, Walter M. ;

Szczylik, Cezary ;

Oudard, Stephane ;

Siebels, Michael ;

Negrier, Sylvie ;

Chevreau, Christine ;

Solska, Ewa ;

Desai, Apurva A. ;

Rolland, Frederic ;

Demkow, Tomasz ;

Hutson, Thomas E. ;

Gore, Martin ;

Freeman, Scott ;

Schwartz, Brian ;

Shan, Minghua ;

Simantov, Ronit ;

Bukowski, Ronald M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (02) :125-134

← 1 2 3 4 →