Efficacy and safety of fruquintinib plus chemotherapy as second-line therapy in metastatic colorectal cancer: A multicenter trial

Wensi Zhao; Jun Lei; Wei Shi; Jun Li; Liping Li; Junping Huang; Wei Gong; Xiongjie Yu; Kefa Yue; Lilin He; Qi Han; Songlin Wang; Ze Tang; Wenbin Li; Dedong Cao; Dandan Lin; Shaobo Ke; Haoqing Zhai; Xianliang Hua; Lei Yin; Yongshun Chen

doi:10.59717/j.xinn-oncol.2026.100026

The Innovation Oncology > 2026 Vol. 1 > No. 2 > 100026

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Efficacy and safety of fruquintinib plus chemotherapy as second-line therapy in metastatic colorectal cancer: A multicenter trial

1.
Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, China
2.
Cancer Center, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, China
3.
Department of Laboratory Medicine, Xixi Hospital of Hangzhou, Hangzhou Medical College, Hangzhou 310060, China
4.
Department of Oncology, Xiaogan Central Hospital, Xiaogan 432099, China
5.
Department of Oncology, Xiantao First People’s Hospital, Xiantao 433000, China
6.
Department of Oncology, Jianghan Oilfield General Hospital, Qianjiang 433124, China
7.
Department of Oncology, Xiangyang Central Hospital, Xiangyang 441106, China
8.
Department of Oncology, Shiyan Renmin Hospital, Shiyan 442099, China
9.
Department of Oncology, People’s Hospital of Yangxin, Huangshi 435299, China
10.
Department of Oncology, First People’s Hospital of Tianmen, Tianmen 431700, China
11.
Department of Oncology, Xianning Central Hospital, Xianning 437100, China
12.
Department of Oncology, Zhongxiang People’s Hospital, Jingmen 431999, China
13.
Department of Oncology, Huangshi Central Hospital, Huangshi 435000, China
14.
Department of Oncology, Qianjiang Central Hospital of Yangtz University, Qianjiang 433100, China
15.
Department of Pediatric Research Institute Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Intelligent Application of Big Data in Pediatrics Engineering Research Center of Chongqing Education Commission of China, Chongqing 400016, China
16.
These authors contributed equally

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Corresponding authors: yongshun2007@163.com (Y.C.); yinlei@whu.edu.cn (L.Y.)
Received Date: January 04, 2026

Accepted Date: July 06, 2026

Published Online: July 10, 2026

The Innovation Oncology 1(2), https://doi.org/10.59717/j.xinn-oncol.2026.100026 | Cite this article

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. We evaluated fruquintinib plus chemotherapy as second-line therapy in metastatic colorectal cancer (mCRC).
  
  It is the first study of a small-molecule tyrosine kinase inhibitor for mCRC patients at second-line setting.
  
  The real-world mCRC patients with second-line treatment were screened for propensity score matching analysis.
  
  Results showed progression-free survival benefit and favorable safety profile compared to real-world data.
  
  Fruquintinib plus chemotherapy may represent a novel and rational second-line treatment option for mCRC.

ABSTRACT

ABSTRACT

To evaluate the efficacy and safety of fruquintinib combined with chemotherapy as second-line treatment for metastatic colorectal cancer (mCRC), we performed an open-label phase II trial. A total of 102 Chinese mCRC patients who progressed after first-line therapy were enrolled and received fruquintinib plus chemotherapy. Fruquintinib was administered in a standard 4-week regimen or an adjusted 3-week regimen. Primary endpoint was progression-free survival (PFS). Efficacy and adverse events (AEs) were compared to a real-world control group. As of data cutoff on January 10, 2026, with a median follow-up of 33.2 months, the median PFS was 7.1 months (95% CI, 5.4-8.6) and overall survival (OS) was 22.6 months (95% CI, 19.7-26.2). Objective response rate was 27.6% (95% CI: 19.2-37.7), disease control rate (DCR) was 83.7% (95% CI: 74.5-90.1), and median duration of response (DoR) was 11.9 months (95% CI: 8.8-15.0). Patients with primary tumor resection, no liver metastasis, or no prior history of anti-vascular endothelial growth factor (receptor) therapy had improved survival. Grade ≥ 3 AEs occurred in 38.2% of patients, common grade ≥ 3 AEs were neutropenia (11.8%) and leukopenia (5.9%). Compared to the control group, the fruquintinib group showed significantly improved median PFS (6.6 vs. 5.3 months; HR, 0.68, 95% CI, 0.51-0.91; P = 0.010), higher ORR (23.1% vs. 16.9%) and DCR (79.5% vs. 67.7%), and a numerically longer OS (23.0 vs. 19.7 months; P = 0.640). These results showed fruquintinib plus chemotherapy may represent a novel and rational second-line option for mCRC with promising efficacy and favorable safety.
- metastatic colorectal cancer /
- fruquintinib /
- chemotherapy /
- second-line treatment /
- progression-free survival

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Zhao W., Lei J., Shi W., et al. (2026). Efficacy and safety of fruquintinib plus chemotherapy as second-line therapy in metastatic colorectal cancer: A multicenter trial. The Innovation Oncology 1:100026. https://doi.org/10.59717/j.xinn-oncol.2026.100026

Zhao W., Lei J., Shi W., et al. (2026). Efficacy and safety of fruquintinib plus chemotherapy as second-line therapy in metastatic colorectal cancer: A multicenter trial. The Innovation Oncology 1:100026. https://doi.org/10.59717/j.xinn-oncol.2026.100026

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Efficacy and safety of fruquintinib plus chemotherapy as second-line therapy in metastatic colorectal cancer: A multicenter trial

GRAPHICAL ABSTRACT

PUBLIC SUMMARY

ABSTRACT