Subgroup Analysis by Liver Metastasis in the FRESCO Trial Comparing Fruquintinib versus Placebo Plus Best Supportive Care in Chinese Patients with Metastatic Colorectal Cancer

Shukui Qin; Rui-Hua Xu; Lin Shen; Jianming Xu; Yuxian Bai; Lei Yang; Yanhong Deng; Zhen-Dong Chen; Haijun Zhong; Hongming Pan; Weijian Guo; Yongqian Shu; Ying Yuan; Jianfeng Zhou; Nong Xu; Tianshu Liu; Dong Ma; Changping Wu; Ying Cheng; Donghui Chen; Wei Li; Sanyuan Sun; Zhuang Yu; Peiguo Cao; Haihui Chen; Jiejun Wang; Shubin Wang; Hongbing Wang; Ning Wang; Bin Zhang; Qiang Zhang; Weiguo Su; Xiaojun Guo; Jin Li

doi:10.2147/OTT.S307273

Subgroup Analysis by Liver Metastasis in the FRESCO Trial Comparing Fruquintinib versus Placebo Plus Best Supportive Care in Chinese Patients with Metastatic Colorectal Cancer

Onco Targets Ther. 2021 Aug 11:14:4439-4450. doi: 10.2147/OTT.S307273. eCollection 2021.

Authors

Shukui Qin¹, Rui-Hua Xu², Lin Shen³, Jianming Xu⁴, Yuxian Bai⁵, Lei Yang⁶, Yanhong Deng⁷, Zhen-Dong Chen⁸, Haijun Zhong⁹, Hongming Pan¹⁰, Weijian Guo¹¹, Yongqian Shu¹², Ying Yuan¹³, Jianfeng Zhou¹⁴, Nong Xu¹⁵, Tianshu Liu¹⁶, Dong Ma¹⁷, Changping Wu¹⁸, Ying Cheng¹⁹, Donghui Chen²⁰, Wei Li²¹, Sanyuan Sun²², Zhuang Yu²³, Peiguo Cao²⁴, Haihui Chen²⁵, Jiejun Wang²⁶, Shubin Wang²⁷, Hongbing Wang²⁸, Ning Wang²⁹, Bin Zhang²⁹, Qiang Zhang²⁹, Weiguo Su³⁰, Xiaojun Guo³⁰, Jin Li³¹

Affiliations

¹ Cancer Center, Jinling Hospital, Nanjing, People's Republic of China.
² Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China.
³ Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
⁴ Department of Medical Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People's Republic of China.
⁵ Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, People's Republic of China.
⁶ Department of Medical Oncology, Nantong Cancer Hospital, Nantong, People's Republic of China.
⁷ Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.
⁸ Department of Medical Oncology, The Second Hospital of Anhui Medical University, Hefei, People's Republic of China.
⁹ Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China.
¹⁰ Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
¹¹ Department of Medical Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
¹² Department of Medical Oncology, Jiangsu Provincial Hospital, Nanjing, People's Republic of China.
¹³ Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
¹⁴ Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, People's Republic of China.
¹⁵ Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, People's Republic of China.
¹⁶ Department of Medical Oncology, Fudan University Zhongshan Hospital, Shanghai Medical College, Shanghai, People's Republic of China.
¹⁷ Department of Medical Oncology, Guangdong Provincial People's Hospital, Guangzhou, People's Republic of China.
¹⁸ Department of Medical Oncology, The First People's Hospital of Changzhou, Changzhou, People's Republic of China.
¹⁹ Department of Medical Oncology, Jilin Province Cancer Hospital, Changchun, People's Republic of China.
²⁰ Department of Medical Oncology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, People's Republic of China.
²¹ Department of Medical Oncology, The First Hospital of Jilin University, Changchun, People's Republic of China.
²² Department of Medical Oncology, Xuzhou Central Hospital, Xuzhou, People's Republic of China.
²³ Department of Medical Oncology, The Affiliated Hospital of Medical College Qingdao University, Qingdao, People's Republic of China.
²⁴ Department of Medical Oncology, The Third Xiangya Hospital of Central South University, Changsha, People's Republic of China.
²⁵ Department of Medical Oncology, Liuzhou Worker's Hospital, Liuzhou, People's Republic of China.
²⁶ Department of Medical Oncology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
²⁷ Department of Medical Oncology, Peking University Shenzhen Hospital, Beijing University, Shenzhen, People's Republic of China.
²⁸ Department of Medical Oncology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou Medical College, Xuzhou, People's Republic of China.
²⁹ Eli Lilly and Company, Shanghai, People's Republic of China.
³⁰ Hutchison MediPharma Limited, Shanghai, People's Republic of China.
³¹ Department of Medical Oncology, Tongji University Shanghai East Hospital, Shanghai, People's Republic of China.

Abstract

Objective: The aim of the present subgroup analysis of the FRESCO trial is to determine the efficacy and hepatotoxicity of fruquintinib in Chinese patients with metastatic CRC with liver metastasis (CRLM) who were receiving third-line or posterior-line therapy.

Methods: Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Hazard ratio (HR) was estimated through Cox proportional hazards model. Hepatotoxicity was coded using the standardized MedDRA queries of hepatic failure, fibrosis, cirrhosis, and other liver injury-related conditions and graded using the Common Terminology Criteria Adverse Events grades. The efficacy of fruquintinib in patients with CRLM was evaluated in various subgroups.

Results: A total of 287 (69.0%) patients with metastatic CRC had liver metastasis (LM, fruquintinib: 185 and placebo: 102). Median OS in patients with CRLM was significantly prolonged with fruquintinib compared with placebo (8.61 months vs 5.98 months; HR=0.59, 95% CI, 0.45-0.77, P<0.001). In patients with CRLM, the incremental median PFS for patients in the fruquintinib-treated group was significantly higher than in the placebo group (median PFS: 3.71 vs.1.84 months; HR=0.22, 95% CI: 0.17-0.30; P<0.001). Compared with placebo, significant improvements in OS were observed with fruquintinib in LM patients regardless of lung metastasis, prior target therapy, and K-RAS status. In patients with CRLM, treatment-emergent hepatotoxicities of any grade occurred in 7 (3.8%) patients in the fruquintinib group vs 2 (2.0%) in the placebo group.

Conclusion: Fruquintinib demonstrated a statistically significant increase in OS and PFS as compared with placebo in Chinese patients with CRLM. The hepatotoxicity of fruquintinib was less reported, and comparable with placebo in patients with CRLM.

Clinicaltrialsgov identifier: NCT02314819.

Keywords: FRESCO trial; colorectal cancer; fruquintinib; liver metastasis.

Associated data

ClinicalTrials.gov/NCT02314819

Grants and funding

The FRESCO trial was co-funded by Eli Lilly and Company (Indianapolis, IN, USA) and Hutchison MediPharma (Shanghai, China). The role of the funding source includes study design, data acquisition, analysis and interpretation of data, and the decision to submit the article for publication. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. Medical writing assistance support for this publication was funded by Eli Lilly and Company.