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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REFERENCES

[1]	Sung H., Ferlay J., Siegel R.L., et al. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71:209−249. DOI:10.3322/caac.21660 View in Article CrossRef Google Scholar
[2]	Wang S., Zheng R., Li J., et al. (2024). Global, regional, and national lifetime risks of developing and dying from gastrointestinal cancers in 185 countries: A population-based systematic analysis of GLOBOCAN. Lancet Gastroenterol. Hepatol. 9:229−237. DOI:10.1016/S2468-1253(23)00366-7 View in Article CrossRef Google Scholar
[3]	Han B., Zheng R., Zeng H., et al. (2024). Cancer incidence and mortality in China, 2022. J. Natl. Cancer Cent. 4:47−53. DOI:10.1016/j.jncc.2024.01.006 View in Article CrossRef Google Scholar
[4]	Benson A.B., Venook A.P., Al-Hawary M.M., et al. (2021). Colon cancer, version 2.2021, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Cancer Netw. 19:329-359. DOI:10.6004/jnccn.2021.0012 View in Article Google Scholar
[5]	Benson A.B., Venook A.P., Al-Hawary M.M., et al. (2022). Rectal cancer, version 2.2022, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Cancer Netw. 20:1139-1167. DOI:10.6004/jnccn.2022.0051 View in Article Google Scholar
[6]	Biller L.H. and Schrag D. (2021). Diagnosis and treatment of metastatic colorectal cancer: A review. JAMA 325:669−685. DOI:10.1001/jama.2021.0106 View in Article CrossRef Google Scholar
[7]	De Falco V., Napolitano S., Rosello S., et al. (2020). How we treat metastatic colorectal cancer. ESMO Open 4:e000813. DOI:10.1136/esmoopen-2020-000813 View in Article CrossRef Google Scholar
[8]	Bennouna J., Sastre J., Arnold D., et al. (2013). Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): A randomised phase 3 trial. Lancet Oncol. 14:29−37. DOI:10.1016/S1470-2045(12)70477-1 View in Article CrossRef Google Scholar
[9]	Masi G., Salvatore L., Boni L., et al. (2015). Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: Final results of the randomized BEBYP trial. Ann. Oncol. 26:724−730. DOI:10.1093/annonc/mdv012 View in Article CrossRef Google Scholar
[10]	Tabernero J., Yoshino T., Cohn A.L., et al. (2015). Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): A randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 16:499−508. DOI:10.1016/S1470-2045(15)70127-0 View in Article CrossRef Google Scholar
[11]	Van Cutsem E., Tabernero J., Lakomy R., et al. (2012). Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J. Clin. Oncol. 30:3499−3506. DOI:10.1200/JCO.2012.42.8201 View in Article CrossRef Google Scholar
[12]	Grothey A., Van Cutsem E., Sobrero A., et al. (2013). Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet (London, England) 381:303−312. DOI:10.1016/S0140-6736(12)61900-X View in Article CrossRef Google Scholar
[13]	Li J., Qin S., Xu R.H., et al. (2018). Effect of fruquintinib vs placebo on overall survival in patients with previously treated metastatic colorectal cancer: The FRESCO randomized clinical trial. JAMA 319:2486−2496. DOI:10.1001/jama.2018.7855 View in Article CrossRef Google Scholar
[14]	Dasari A., Lonardi S., Garcia-Carbonero R., et al. (2023). Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): An international, multicentre, randomised, double-blind, phase 3 study. Lancet (London, England) 402:41−53. DOI:10.1016/S0140-6736(23)00772-9 View in Article CrossRef Google Scholar
[15]	Ma S., Chen R., Duan L., et al. (2023). Efficacy and safety of toripalimab with fruquintinib in the third-line treatment of refractory advanced metastatic colorectal cancer: Results of a single-arm, single-center, prospective, phase II clinical study. J Gastrointest. Oncol. 14:1052−1063. DOI:10.21037/jgo-23-108 View in Article CrossRef Google Scholar
[16]	Zhao W., Lei J., Ke S., et al. (2023). Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: An open-label, single-arm, phase II trial (RENMIN-215). EClinicalMedicine 66:102315. DOI:10.1016/j.eclinm.2023.102315 View in Article CrossRef Google Scholar
[17]	Ma X., Ou K., Liu X., et al. (2026). Efficacy and safety of fruquintinib combined with albumin-bound paclitaxel as second-line therapy for advanced gastric cancer following failure of PD-1 inhibitor-containing treatment (TACTIC GC-01): A phase II single-arm study. Int. J. Cancer 158:2219−2228. DOI:10.1002/ijc.70299 View in Article CrossRef Google Scholar
[18]	Zhang Y., Wang Z.X., Shen L., et al. (2023). A phase Ib/II study of fruquintinib in combination with paclitaxel as the second-line therapy for advanced gastric cancer. Cancer Commun. (Lond) 43:150−153. DOI:10.1002/cac2.12379 View in Article CrossRef Google Scholar
[19]	Zhang X., Zhao T., Zheng B., et al. (2025). Fruquintinib as first-line or second-line treatment in unresectable or metastatic soft-tissue sarcoma: A prospective, single-arm phase II study. Clin. Transl. Med. 15:e70308. DOI:10.1002/ctm2.70308 View in Article CrossRef Google Scholar
[20]	Bang Y.J., Kang Y.K., Kang W.K., et al. (2011). Phase II study of sunitinib as second-line treatment for advanced gastric cancer. Invest. New Drugs 29:1449−1458. DOI:10.1007/s10637-010-9438-y View in Article CrossRef Google Scholar
[21]	Martin-Richard M., Gallego R., Pericay C., et al. (2013). Multicenter phase II study of oxaliplatin and sorafenib in advanced gastric adenocarcinoma after failure of cisplatin and fluoropyrimidine treatment. A GEMCAD study. Invest. New Drugs 31:1573−1579. DOI:10.1007/s10637-013-0020-2 View in Article CrossRef Google Scholar
[22]	Guo Y., Zhang W., Ying J., et al. (2023). Phase 1b/2 trial of fruquintinib plus sintilimab in treating advanced solid tumours: The dose-escalation and metastatic colorectal cancer cohort in the dose-expansion phases. Eur. J. Cancer 181:26−37. DOI:10.1016/j.ejca.2022.12.004 View in Article CrossRef Google Scholar
[23]	Ciardiello F., Ciardiello D., Martini G., et al. (2022). Clinical management of metastatic colorectal cancer in the era of precision medicine. CA Cancer J. Clin. 72:372−401. DOI:10.3322/caac.21728 View in Article CrossRef Google Scholar
[24]	Giantonio B.J., Catalano P.J., Meropol N.J., et al. (2023). Bevacizumab in combination with Oxaliplatin, Fluorouracil, and Leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the eastern cooperative oncology group study E3200. J. Clin. Oncol. 41:3670−3675. DOI:10.1200/JCO.22.02761 View in Article CrossRef Google Scholar
[25]	Iwamoto S., Takahashi T., Tamagawa H., et al. (2015). FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: The randomized phase III EAGLE study. Ann. Oncol. 26:1427−1433. DOI:10.1093/annonc/mdv197 View in Article CrossRef Google Scholar
[26]	Peeters M., Price T.J., Cervantes A., et al. (2010). Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J. Clin. Oncol. 28:4706−4713. DOI:10.1200/JCO.2009.27.6055 View in Article CrossRef Google Scholar
[27]	Sobrero A.F., Maurel J., Fehrenbacher L., et al. (2008). EPIC: Phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J. Clin. Oncol. 26:2311−2319. DOI:10.1200/JCO.2007.13.1193 View in Article CrossRef Google Scholar
[28]	Cardone C., De Stefano A., Rosati G., et al. (2023). Regorafenib monotherapy as second-line treatment of patients with RAS-mutant advanced colorectal cancer (STREAM): An academic, multicenter, single-arm, two-stage, phase II study. ESMO Open 8:100748. DOI:10.1016/j.esmoop.2022.100748 View in Article CrossRef Google Scholar
[29]	Wu L., Yan H., Qin Y., et al. (2024). Fruquintinib plus oxaliplatin combined with S-1 (SOX) as neoadjuvant therapy for locally advanced gastric cancer (GC) or gastro-oesophageal junction adenocarcinoma (GEJ): A multicentre, phase II, single-arm, open-label clinical trial (FRUTINEOGA) protocol. BMJ Open 14:e075696. DOI:10.1136/bmjopen-2023-075696 View in Article CrossRef Google Scholar
[30]	Wang F., Shen L., Guo W., et al. (2024). Fruquintinib plus paclitaxel versus placebo plus paclitaxel for gastric or gastroesophageal junction adenocarcinoma: The randomized phase 3 FRUTIGA trial. Nat. Med. 30:2189−2198. DOI:10.1038/s41591-024-02989-6 View in Article CrossRef Google Scholar
[31]	Song Y., Qu T., Zhang H., et al. (2021). The real-world practice of Fruquintinib for Chinese patients with metastatic colorectal cancer. Cancer Manag. Res. 13:6199−6205. DOI:10.2147/CMAR.S313275 View in Article CrossRef Google Scholar
[32]	Bai Y., Qin S., Li J., et al. (2020). Early carcinoembryonic antigen (CEA) dynamics to predict fruquintinib efficacy in FRESCO, a 3+ line metastatic colorectal carcinoma (mCRC) phase III trial. J. Clin. Oncol. 38:e16001. DOI:10.1200/JCO.2020.38.15_suppl.e16001 View in Article CrossRef Google Scholar

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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