Maintenance Chemotherapy With S-1 vs. Observation After Adjuvant Therapy for Resected Pancreatic Cancer With High Risk of Recurrence/Metastasis

Prior treatment

• Incomplete macroscopic resection (R2 resection);
• CA19-9 \> 180 U/mL within 21 days before enrollment;
• Participation in another clinical trial of cytotoxic drugs, targeted therapies, immunotherapies, etc., within the past 4 weeks, or received systemic chemotherapy, radiotherapy, or biological therapy within the past 4 weeks;
• Concurrent or metachronous cancers with disease-free survival ≥ 5 years (excluding pancreatic cancer), except for cancers that have been cured or can be potentially cured with local excision (e.g., esophageal cancer, gastric cancer, colorectal cancer, cervical cancer, non-melanoma skin cancer, bladder cancer);
• Known allergy to the investigational drug, the class of the investigational drug, or its components;
• Need for systemic corticosteroid treatment (except for local steroid pre-treatment);
• Toxicity not recovered (CTCAE \> Grade 1) or previous anticancer surgery not fully recovered;

Other illness

• Pancreatic cancer originating from non-pancreatic ductal epithelium, including pancreatic neuroendocrine tumors, pancreatic acinar cell carcinoma, pancreatoblastoma, and solid-pseudopapillary tumor;
• Presence of distant metastasis (including malignant ascites and pleural effusion, peritoneal metastasis) or locally recurrent pancreatic cancer;
• Factors that significantly affect oral drug absorption, such as difficulty swallowing, chronic diarrhea, or gastrointestinal obstruction; uncontrolled Crohn's disease or ulcerative colitis;
• History of interstitial lung disease (including interstitial pneumonia, pulmonary fibrosis, etc.) or CT findings of interstitial lung disease;
• Active local or systemic infection requiring treatment;
• Heart failure NYHA classification ≥ II or severe heart disease;
• Known HIV infection or history of acquired immunodeficiency syndrome (AIDS) or active hepatitis B or C;

Lab values

• Severe liver dysfunction (AST/ALT \> 3.5 times the upper limit of normal, alkaline phosphatase \> 6 times the upper limit of normal), with liver drainage;

Other

• Known peripheral neuropathy (CTCAE ≥ Grade 2);
• Clinically symptomatic serous effusions (including pleural effusion, ascites, pericardial effusion) requiring symptomatic treatment;
• Pregnant or breastfeeding women; patients of childbearing potential unwilling or unable to take effective contraceptive measures;
• Patients deemed unsuitable for this study by the investigator.

• Histologically confirmed pancreatic cancer (originating from the pancreatic ductal epithelium);
• Meets one of the following conditions: Pathologically confirmed as moderately differentiated, moderately to poorly differentiated, or poorly differentiated; or pathologic staging as: T3N0M0, T1-3N1-2M0, T4N0-2M0; or one or more surgical margins are R1 resected (R0 resection if no tumor cells are found more than 1mm from the margin, otherwise R1 resection); or involvement of the portal vein and/or superior mesenteric vein resection; or pre-adjuvant chemotherapy CA19-9 \> 90 U/mL; or pre-adjuvant chemotherapy ctDNA testing positive;
• Completed standard treatment: Received radical resection, postoperative adjuvant therapy (including adjuvant chemotherapy based on gemcitabine or fluorouracil), and radiotherapy (if applicable);
• Eligible for oral medication;
• Age ≥18 and ≤75, male or female;
• ECOG performance status: 0 to 2;
• Normal function of major organs as per the following criteria within 14 days prior to starting treatment:① Neutrophil count ≥ 1.5×10\^9/L;② Platelet count ≥ 75×10\^9/L;③ Hemoglobin ≥ 9.0 g/dL;④ AST ≤ 2.5×UNL (upper normal limit) (if liver metastasis present, AST ≤ 5×UNL);⑤ ALT ≤ 2.5×UNL (if liver metastasis present, ALT ≤ 5×UNL);⑥ Total bilirubin ≤ 1.5×UNL;⑦ Creatinine clearance (calculated using the Cockcroft-Gault formula) \> 60 mL/min or serum creatinine ≤ 1.5×UNL;
• Women of childbearing potential must have used reliable contraception within 7 days prior to enrollment and have a negative pregnancy test, and must be willing to use appropriate contraception during the study and for 6 months after the last dose of the investigational drug. For men, they must be surgically sterile or agree to use appropriate contraception during the study and for 3 months after treatment;
• Expected survival time ≥6 months;
• Voluntary participation in the study, signed informed consent, and demonstrated good compliance and cooperation during follow-up.