Fruquintinib Combined With PD-1 Inhibitor as First-line Maintenance Therapy for Advanced Gastric Cancer

Inclusion Criteria:

• Voluntarily signed the informed consent and had good compliance;

• Age ≥18 years, Eastern Cooperative Oncology Group (ECOG) score 0-1, and expectedsurvival time ≥12 months;

• Histologically or cytologically unresectable, locally advanced, recurrent ormetastatic gastric or gastroesophageal junction adenocarcinoma;

• He had not received previous systemic chemotherapy for unresectable, locallyadvanced, recurrent, or metastatic gastric or gastroesophageal junctionadenocarcinoma;

• Patients with disease progression/relapse occurring more than 6 months aftercompletion of neoadjuvant/adjuvant therapy;

• At least one measurable lesion according to RECIST version 1.1;

• Tumor tissue/serum samples were tested as microsatellite stable (MSS) or mismatchrepair intact (pMMR), HER2 negative;

• Adequate organ functions:

Absolute neutrophil count ≥1.5×109/L; Platelet ≥100×109/L; Hemoglobin ≥90g/L; WBC≥3×109/L Total bilirubin ≤ 1.5XULN; ALT and AST ≤2.5XULN (If liver metastasis, AST and ALT≤5 XULN)； Serum creatinine (Cr) ≤1.5XULN or serum creatinine clearance ≥50 ml/min； Urinary protein ≤2+, or 24-hour urinary protein volume ≤2000mg; Prothrombin time (PT) and partially activated prothrombin time (APTT) ≤1.5×ULN;

• Female or male patients of reproductive age must use effective contraception throughout and for 6 months after treatment.

Exclusion Criteria:

• Participated in other drug clinical trials within 4 weeks before enrollment;

• Have had other malignancies within the past 5 years, except cured basal cellcarcinoma of the skin, papillary carcinoma of the thyroid, superficial bladder,carcinoma in situ of the breast, and carcinoma in situ of the cervix ;

• History of severe heart disease, such as symptomatic congestive heart failure (CHF) ≥ grade 2 (NCI-CTCAE 5.0), heart failure ≥ grade 2 New York Heart Association (NYHA), transmural myocardial infarction, unstable angina, poorly controlledarrhythmia, etc.

• Hypertension poorly controlled by two antihypertensive drugs (systolic bloodpressure ≥160mmHg or diastolic blood pressure ≥100mmHg) and type 2 diabetesuncontrolled by antidiabetic treatment (fasting blood glucose ≥8.9mmol/L);

• Active autoimmune and inflammatory diseases, such as systemic lupus erythematosus,psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory boweldisease, and Hashimoto's thyroiditis;

• Type 1 diabetes mellitus, hypothyroidism that can be controlled only withreplacement therapy, and skin diseases (e.g., vitiligo, psoriasis) that do notrequire systemic treatment could be included;

• Central nervous system (CNS) metastases that are not adequately treated, or thepresence of uncontrolled or symptomatic active CNS metastases; Patients withadequately treated CNS metastases and neurologic symptoms that had returned tobaseline at least 4 weeks before enrollment (with the exception of residual signs orsymptoms related to CNS therapy) were eligible for enrollment; In addition,participants had to discontinue corticosteroids or to be taking a stable or taperingdose of prednisone (or equivalent doses of other corticosteroids) of 10 mg or lessper day at least 4 weeks before enrollment;

• The patients had pleural effusion and ascites that could not be controlled bypuncture drainage and other treatments within 14 days before enrollment. Moderate orgreater pericardial effusion with clinical symptoms;

• A live or attenuated live vaccine was administered within 30 days before enrollment;

• Major surgery had been performed within 28 days before enrollment or minornonstudy-related surgery had been performed within 7 days before enrollment (withthe exception of tumor biopsy and venous-access port placement);

• Patients with clinically significant bleeding symptoms or definite bleeding tendencywithin 3 months before enrollment; Patients with gastrointestinal perforation and/orgastrointestinal fistula within 6 months before enrollment (except those whosesymptoms disappeared after gastric cancer resection for bleeding/perforation ofgastric cancer);

• Arterial/venous thrombotic events, such as cerebrovascular accident (includingtransient ischemic attack, cerebral infarction), deep vein thrombosis and pulmonaryembolism, occurred within 6 months beforeenrollment;

• Major vascular disease (e.g., aortic aneurysm requiring surgical repair or recentperipheral thrombosis) within 6 months before enrollment;

• Severe, unhealed or open wounds and active ulcers or untreated fractures;

• Had a history of immediate anaphylaxis;

• The presence of clinically significant pulmonary fibrosis or interstitial pneumoniaas judged by the investigator; Had active lung infection prior to injection andrequired anti-infective therapy;

• Active infections included tuberculosis (medical history, investigator's judgment,radiological examination, and local laboratory testing), hepatitis B (hepatitis Bsurface antigen positive and HBV DNA above the upper limit of the study center'snormal range), hepatitis C (HCV antibody positive and HVC RNA positive), HIV (HIVantibody positive), syphilis, etc;

• Had active gastrointestinal bleeding or hemoptysis;

• A history of alcohol or psychotropic substance abuse with no withdrawal or a historyof mental disorder;

• Known allergy to the study drug or any of its excipients; Or severe allergicreactions to other monoclonal antibodies;

• Systemic antibiotic use for ≥ 7 days within 4 weeks before enrollment or unexplainedfever >38.5°C during screening or before the first dose (fever due to a neoplasticcause, as judged by the investigator, was eligible);

• Known history of allogeneic organ transplantation or allogeneic hematopoietic stemcell transplantation;

• Unable to take oral medication;

• The presence of other serious physical or mental illnesses or laboratoryabnormalities that may increase the risk of participating in the study, or interferewith the results of the study, and patients who were deemed by the investigators tobe unsuitable for participation in the study.