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PubMed · 42421558

Randomized phase-II trial of surufatinib plus FOLFOX/FOLFIRI versus FOLFOXIRI as second-line therapy for metastatic colorectal cancer.

Liyu Su·Peicheng Lin·Yi Yin·Zaisheng Ye·Changhua Zhuo·Shenghong Wei·Shichao Yu·Jinluan Li·Yanni Hong·Liang Zheng·Shen Zhao·Ying Chen·Hui Li·Rongbo Lin
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Abstract

BACKGROUND: Second-line treatment for metastatic colorectal cancer (mCRC) typically involves oxaliplatin- or irinotecan-based doublet chemotherapy with or without anti-angiogenic antibodies. Triplet regimens such as FOLFOXIRI have demonstrated synergy and improved efficacy as first-line therapy. Surufatinib, an oral multi-kinase inhibitor targeting VEGFR1-3, FGFR1, and CSF-1R, may enhance chemotherapy efficacy. We evaluated surufatinib combined with doublet (FOLFOX/FOLFIRI) versus triplet (FOLFOXIRI) chemotherapy as second-line treatment for mCRC. PATIENTS AND METHODS: This multicentre, open-label, randomized phase-II trial used Simon's minimax two-stage design. Eligible patients had mCRC progressing on or within 6 months after first-line doublet chemotherapy. Patients were randomized 1:1 to surufatinib 250 mg once daily plus either mFOLFOX6/FOLFIRI (doublet cohort, selected based on prior regimen) or FOLFOXIRI (triplet cohort). The primary endpoint was objective response rate (ORR). RESULTS: From September 2021 to November 2023, 57 patients were randomized (28 per cohort after one withdrawal). In the doublet cohort, ORR was 35.7% (95% CI: 18.6-55.9), median progression-free survival (PFS) was 5.4 months (95% CI: 3.8-7.0), and median overall survival (OS) was 19.0 months (95% CI: 9.2-28.8). In the triplet cohort, ORR was 39.3% (95% CI: 21.5-59.4), median PFS was 5.8 months (95% CI: 3.3-8.2), and median OS was 10.9 months (95% CI: 6.0-15.8). Grade ≥3 treatment-emergent adverse events occurred more frequently in the triplet (71.4%) versus doublet (57.1%) cohort, with higher rates of treatment delays (89.3% versus 72.0%) and discontinuations (25.0% versus 14.3%). CONCLUSIONS: Surufatinib plus doublet chemotherapy showed encouraging antitumor activity and acceptable tolerability in second-line mCRC, warranting further evaluation in a larger randomized trial. In contrast, surufatinib plus triplet chemotherapy was associated with increased toxicity, more frequent treatment delays or discontinuations, and shorter overall survival; this combination is not recommended for further investigation in this setting.ClinicalTrials.gov: NCT04734249Date of registration: January 31, 2021.

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HumansAntineoplastic Combined Chemotherapy ProtocolsColorectal NeoplasmsFemaleLeucovorinFluorouracilMaleOrganoplatinum CompoundsMiddle AgedAgedCamptothecinAdultNeoplasm MetastasisMetastatic colorectal cancerangiogenesis inhibitorsdoublet chemotherapysecond-line treatmentsurufatinibtriplet chemotherapyJournal ArticleRandomized Controlled TrialMulticenter StudyClinical Trial, Phase IIComparative StudyResearch Support, Non-U.S. Gov't

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Liyu Su, Peicheng Lin, Yi Yin, Zaisheng Ye, Changhua Zhuo, Shenghong Wei, Shichao Yu, Jinluan Li, Yanni Hong, Liang Zheng, Shen Zhao, Ying Chen, Hui Li, Rongbo Lin. 2026-07-09. Randomized phase-II trial of surufatinib plus FOLFOX/FOLFIRI versus FOLFOXIRI as second-line therapy for metastatic colorectal cancer.. https://doi.org/10.1080/07853890.2026.2698360

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Adult subjectAged subjectAntineoplastic Combined Chemotherapy Protocols subjectCamptothecin subjectClinical Trial, Phase II subjectColorectal Neoplasms subjectComparative Study subjectFemale subjectFluorouracil subjectHumans subjectJournal Article subjectLeucovorin subjectMale subjectMetastatic colorectal cancer subjectMiddle Aged subjectMulticenter Study subject

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