Fruquintinib vs Bevacizumab Combined With Irinotecan Liposome and Capecitabine as Second-Line Therapy for Advanced Metastatic Colorectal Cancer

Prior treatment

• History of major surgery or severe trauma within 4 weeks prior to the initiation of the study drug.
• Use of immunosuppressive agents, including systemic or locally absorbed corticosteroids, for immunosuppressive purposes, with a daily dose of prednisone \>10 mg or equivalent, and continued us within 2 weeks prior to enrollment.
• Prior exposure to any irinotecan-containing chemotherapy regimen.
• Reception of live attenuated vaccines within 4 weeks prior to the initiation of the study drug.
• Prior treatment with anti-angiogenic small-molecule targeted therapy.
• Patients with evidence or history of significant bleeding tendency within 3 months prior to enrollment (bleeding \>30 mL within 3 months, vomiting blood, black stool, blood in stool), hemoptysis (\>5 mL of fresh blood within 4 weeks), or a thromboembolic event (including stroke events and/or transient ischemic attack) within 12 months;
• Female participants who are pregnant (positive pregnancy test prior to drug administration) or are breastfeeding;.

Other illness

• Presence of any active autoimmune disease or a history of autoimmune disorders (e.g., autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypopituitarism, vasculitis, nephritis and etc.; not include vitiligo or childhood asthma that has fully resolved and does not require intervention in adulthood; asthma requiring bronchodilator therapy for medical management is included).
• History of other malignancies within the past 5 years, except for curatively resected skin basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ.
• Congenital or acquired immunodeficiency (e.g., HIV) or active hepatitis (e.g., hepatitis B: HBsAg positive and HBV DNA ≥ 10⁴ copies/mL or \>2000 IU/mL; hepatitis C: HCV antibody positive).
• Uncontrolled cardiac clinical symptoms or diseases, including: (1) NYHA classification \>2 heart failure; (2) Unstable angina pectoris; (3) Myocardial infarction within 1 year; (4) Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
• Hypertension that is not well-controlled with antihypertensive medication (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg).
• Active or uncontrolled severe infections (≥ CTCAE grade 2 infection).
• Active peptic ulcer disease, ulcerative colitis, or uncontrolled gastrointestinal bleeding, or any gastrointestinal condition judged by the investigator, which may cause gastrointestinal bleeding, perforation, or bowel obstruction.
• Patients who are allergic to the study drug or excipients.
• Any other conditions judged by the investigator which can potentially affect the study outcomes or compromise the safety or adherence of the participants, such as drug abuse, serious diseases (including psychiatric conditions like epilepsy), or other medical, psychological, or social factors that may endanger participant safety or adherence.

Other

• Urine routine suggests urinary protein ≥2+ and the amount of urinary protein \>1.0g in 24 hours.

• Patients voluntarily enrolled in the study and signed an informed consent form, were compliant and cooperated with follow-up visits;
• Patients with metastatic colorectal adenocarcinoma confirmed by pathology or histology;
• Age: 18-75 (inclusive of 18 and 75), male or female;
• Patients who have previously failed or were intolerant to first-line standard therapy (recurrence within 6 months of the end of adjuvant chemotherapy is considered first-line treatment failure).
• ECOG score: 0-1;
• At least one measurable lesion (based on RECIST 1.1 criteria);
• Major organs and bone marrow function were essentially normal (no blood components or cell growth factors had been used in the 14 days prior to enrollment):
  • Neutrophil count ≥ 1.5 × 10⁹/L;
  • Platelet count ≥ 100 × 10⁹/L;
  • Hemoglobin ≥ 90 g/L;
  • Coagulation parameters: International Normalized Ratio (INR) ≤ 1.5 × ULN; Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN;
  • Liver function: Total bilirubin ≤ 1.5 × ULN; Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 × ULN (with an exception for patients with liver metastases, where ALT/AST may be up to 5 × ULN);
  • Renal function: Serum creatinine ≤ 1.5 × ULN; Creatinine clearance (CCr) ≥ 50 mL/min.
• Female participants of reproductive age must undergo a serum or urinalysis that shows no pregnancy within 14 days before the first dose of study treatment. Male or female patients of childbearing potential will voluntarily use an effective method of contraception, e.g., double-barrier contraception, condoms, oral or injectable contraceptives, intrauterine devices, etc., during the study period and for at least 6 months after the last dose of study medication.