A multi-center effectiveness comparison study of fruquintinib with constructed external control cohort of other targeted kinase inhibitors using real-world data in third-line treatment of metastatic colorectal cancer

Ying Jin; Jin Li; Lin Shen; Jianming Xu; Yanqiao Zhang; Jingdong Zhang; Hongming Pan; Xiujuan Qu; Yamin Chen; Qiang Zhang; Jinnan Li; Miaomiao Sun; Shukui Qin

doi:10.3389/fonc.2022.1044328

A multi-center effectiveness comparison study of fruquintinib with constructed external control cohort of other targeted kinase inhibitors using real-world data in third-line treatment of metastatic colorectal cancer

Front Oncol. 2022 Nov 24:12:1044328. doi: 10.3389/fonc.2022.1044328. eCollection 2022.

Authors

Ying Jin¹, Jin Li², Lin Shen³, Jianming Xu⁴, Yanqiao Zhang⁵, Jingdong Zhang⁶, Hongming Pan⁷, Xiujuan Qu⁸, Yamin Chen⁹, Qiang Zhang¹⁰, Jinnan Li¹⁰, Miaomiao Sun¹⁰, Shukui Qin¹¹

Affiliations

¹ Department of Medical Oncology, Sun Yat-Sen University Cancer Centre, Guangzhou, China.
² Department of Medical Oncology, Shanghai Oriental Hospital Affiliated Tongji University East Hospital, Shanghai, China.
³ Department of Gastrointestinal Oncology, Beijing Cancer Hospital, Beijing, China.
⁴ Department of Medical Oncology, The Fifth Medical Centre of Chinese PLA General Hospital, Beijing, China.
⁵ Department of Gastroenterology, Harbin Medical University Cancer Hospital, Harbin, China.
⁶ Department of Gastroenterology, Liaoning Cancer Hospital and Institute, Shenyang, China.
⁷ Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
⁸ Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
⁹ Department of Medical Oncology, First Affiliated Hospital of Dalian Medical University, Dalian, China.
¹⁰ Eli Lilly and Company, Lilly China Drug Development and Medical Affairs Centre, Shanghai, China.
¹¹ Department of Medical Oncology, People's Liberation Army (PLA) Cancer Centre of Jinling Hospital, Nanjing, China.

Abstract

Objective: The objective of this study was to assess the comparative efficacy in third-line setting for metastatic CRC (mCRC) patients using matched population of FRESCO trial with fruquintinib and real-world data with other TKIs.

Materials and methods: The arm of fruquintinib from the FRESCO phase III trial (NCT02314819) included the data of patients with metastatic CRC that progressed after at least two lines of chemotherapy and received fruquintinib treatment. An external control arm was constructed using real-world data (RWD) of patients who received other TKIs based on key eligibility criteria of FRESCO. The baseline characteristics of two arms was balanced by propensity score matching (PSM). The Kaplan-Meier method and Cox proportional hazard model was used to evaluate progression free survival (PFS) and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), respectively.

Results: Overall, 128 patients were successfully matched by PSM in each, fruquintinib and other TKIs group. The patients in fruquintinib group showed significant increase in median PFS than other TKIs (3.71 vs. 2.49 months, HR = 0.67, 95%CI, 0.48-0.94, p = 0.019). In the subgroup analysis, fruquintinib showed a significant benefit in PFS compared with other TKIs among patients undergoing two or three previous chemotherapy regimens (HR 0.58, 95%CI 0.40-0.84; p=0.004), with rectum as primary disease site (HR 0.52, 95%CI 0.31-0.87; p=0.013), with left sided primary tumor location (HR 0.62, 95%CI 0.42-0.90; p=0.011), with multiple metastasis sites (HR 0.68, 95%CI 0.48-0.97; p=0.034) and with lung metastasis (HR 0.65, 95%CI 0.43-0.98; p=0.042).

Conclusion: With the approach of establishing the external control arm from RWD, this study has demonstrated that treatment with fruquintinib significantly prolonged PFS as compared to other TKIs in patients as third-line mCRC treatment.

Keywords: FRESCO; fruquintinib; metastatic colorectal cancer; progression free survival; real-world data; tyrosine kinase inhibitors.