Anlotinib in combination with trifluridine-tipiracil in patients with refractory metastatic colorectal cancers - a phase II, single arm study

Sep 22, 2026

Management of metastatic colorectal cancer in late-line settings remains a major clinical challenge. This phase II, open-label, single-arm study assessed anlotinib combined with trifluridine-tipiracil (FTD-TPI) as a third-line option for patients with refractory mCRC after at least two prior standard regimens. The primary endpoint was objective response rate; secondary endpoints included DCR, PFS, OS, and safety. In 21 enrolled patients, ORR was 10.0% and median PFS was 5.6 months. Neutropenia and thrombocytopenia were the most common grade ≥3 TEAEs.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages6

Reading Time15 min

AccessFree to download

Background

Methods

Results

Conclusion

Key words

Lessons Learned

Trial information

Disease and study design

Endpoints and statistical methods

Drug information

Patient characteristics

Primary assessment method

Anlotinib in combination with trifluridine-tipiracil inpatients with refractory metastatic colorectal cancers: a phase II, single arm study Qing Liu1,2‡, Chi Zhang1,2‡, Mengling Liu1,2, Ke Peng1,2, Xiaojing Xu1,2, Yiyi Yu1,2, Tianshu Liu1,2,3, *,§, 1Cancer Center, Shanghai Key Laboratory of Oncology Target Discovery and Antibody Drug Development, Zhongshan Hospital, Fudan University, Shanghai, China 2Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China 3Center of Evidence-based Medicine, Fudan University, Shanghai, China *Corresponding author: Tianshu Liu, MD, PhD, Department of Medical Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China ([liu.tianshu@zs-hospital.sh.cn](liu.tianshu@zs-hospital.sh.cn)) . ‡Q. Liu and C. Zhang contributed equally. §Principal Investigator. Abstract Background: The management of metastatic colorectal cancer (mCRC) in late-line settings remains a significant clinical challenge. The SUNLIGHT trial, which investigated the combination of trifluridine-tipiracil (FTD-TPI) and bevacizumab, reported a median progression-free survival (PFS) of 5 months and an objective response rate (ORR) of 6.3% . This phase II study was conducted to evaluate the potential of combining anlotinib with FTD-TPI as a third-line treatment strategy in patients with refractory mCRC. Methods: In this open-label, single-arm phase II study, mCRC patients who had experienced disease progression following at least two prior standard treatment regimens were enrolled. Participants received a combination of anlotinib (12 mg, PO, QD, days 1-14, q3w) and FTD-TPI (35 mg/ m2, PO, BID, days 1-5, q2w) . The primary endpoint was the ORR. Secondary endpoints included disease control rate (DCR), PFS, overall survival (OS) and safety. Results: As of May 30, 2025, twenty-one patients with mCRC were enrolled in this study. The median age was 62 years, with 71.4% male participants. Among the 20 evaluable patients, 2 achieved a partial response (PR), 16 had stable disease (SD) at the first evaluation. The ORR was 10.0%(2/20), and the DCR reached 90.0%(18/20) . Based on Kaplan–Meier estimates, the median PFS was 5.6 months. The most common grade ≥3 treatment emergent adverse event (TEAEs) were neutropenia (25%) and thrombocytopenia (5%) . Conclusion: The combination of anlotinib and FTD-TPI demonstrated promising efficacy and a manageable safety profile, supporting its potential as a favorable late-line treatment option for patients with refractory mCRC. [ClinicalTrials.gov](ClinicalTrials.gov) Identifier: ChiCTR2400079535 . Key words: anlotinib; trifluridine-tipiracil; metastatic colorectal cancer; late-line therapy. Lessons Learned • Anlotinib may offer a more convenient alternative to intravenous anti-angiogenic agents in the mCRC treatment for its oral route of administration. • The combination of anlotinib and FTD-TPI showed promising efficacy and manageable toxicity for late-line treatment in patients with mCRC. Received: 27 July 2025; Accepted: 19 January 2026. © The Author(s) 2026. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by-nc/4.0/](licenses/by-nc/4.0/)), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [reprints@oup.com](reprints@oup.com) for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [journals.permissions@oup.com](journals.permissions@oup.com). 2 The Oncologist, 2026, Vol. 31, No. 3 Trial informaTion Disease Stage of disease/treatm

FAQs

What is the study design and treatment regimen in this phase II trial?

This is an open-label, single-arm phase II study. Patients received anlotinib orally on days 1–14 of a 21-day cycle plus FTD-TPI orally twice daily on days 1–5 of each 14-day cycle.

What were the primary and secondary endpoints?

The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

What efficacy results were reported for the evaluable population?

Among 20 evaluable patients, there were 2 partial responses and stable disease in 16 at the first evaluation. ORR was 10.0% (2/20), DCR was 90.0% (18/20), and median PFS was 5.6 months.

What safety findings were highlighted?

The most common grade ≥3 treatment-emergent adverse events were neutropenia (25%) and thrombocytopenia (5%). The study concluded that safety was manageable with the combination.

Sep 22, 2026

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