This is a real-world study. Patients with metastatic colorectal cancer who have progressed (PD) after third-line treatment with fruquintinib combined with PD-1 inhibitors will receive fruquintinib combined with TAS-102 as fourth-line therapy. The objective of this study was to observe the efficacy and safety of cross-line（from third to fourth line）treatment with fruquinitinib.

This is a real-world study. Patients with metastatic colorectal cancer confirmed by histopathology had previously received 2-line system therapy with fluorouracil, oxaliplatin, irinotecan, anti-VEGF, anti-EGFR (RAS and BRAF wild type) (treatment with anti-VEGF-TKI is not allowed), and had received fruquinitinib combined with PD-1 inhibitors for third-line treatment. After progression (PD) (confirmed by RECIST 1.1 ), fruquinitinib combined with TAS-102 as fourth-line therapy was received. The primary endpoint was observation the overall survival (OS) of fourth-line treatment of mCRC with fruquinitinib and TAS-102. The study objective is to explore the possibility of cross-line rechallenge of fruquinitinib.

Inclusion Criteria:

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To be enrolled in this study, patients must meet all of the following criteria:

1. Age ≥18 years, ≤75 years;
2. No gender limitation;
3. Patients with metastatic colorectal cancer confirmed by histopathology had previously received 2-line system therapy with fluorouracil, oxaliplatin, irinotecan, anti-VEGF, anti-EGFR (RAS and BRAF wild type) (treatment with anti-VEGF-TKI is not allowed), and had received fruquinitinib combined with PD-1 inhibitors for third-line treatment. After progression (PD) (confirmed by RECIST 1.1 ), fruquinitinib combined with TAS-102 as fourth-line therapy was received.
4. Expected survival ≥12 weeks
5. Must have at least one measurable lesion (RECIST1.1).
6. Full organ and bone marrow function.

Exclusion Criteria:

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Patients will not be admitted to the study if they meet any of the following criteria:

1. Patients with contraindications to study drugs (fruquinitinib, PD-1 inhibitor, TAS-102);
2. allergic to the investigational drug or any of its adjuncts;
3. There are other non-investigational drugs during third-line and fourth-line treatment;
4. Pregnant or lactating female subjects;
5. Patients with a large number of pleural effusion or ascites requiring drainage;
6. Patients considered unsuitable for inclusion in this study by the investigators.

Patients with metastatic colorectal cancer