Chemotherapy, immune checkpoint inhibitors, and anti-angiogenic targeted therapies have been explored in combination for neoadjuvant and conversion therapies. However, the efficacy of the novel anti-angiogenic agent fruquintinib in combination with immune checkpoint inhibitors and chemotherapy in the neoadjuvant and conversion treatment of locally advanced or metastatic gastric cancer has not been reported. This study aims to observe the efficacy and safety of fruquintinib combined with immune checkpoint inhibitors and chemotherapy in real-world settings.

Inclusion Criteria:

Patients must meet all of the following criteria to be enrolled in this study:

1. Age ≥18 years and ≤75 years;
2. Either gender;
3. Histologically confirmed gastric or gastroesophageal junction adenocarcinoma. For neoadjuvant therapy cohort: candidates for Initial potentially curative surgery with cII, cIII, or cIVA stage disease (>cT2N0-3M0 or cT0-4N+M0); no distant metastasis. For conversion therapy cohort: patients with locally advanced unresectable or stage IV metastatic disease (per AJCC 8th edition). Pre-treatment imaging (CT or MRI, PET-CT, etc.) must indicate only one of the following unresectable factors:

(1) Lymph node metastasis around the abdominal aorta (2) Virchow lymph node metastasis (left supraclavicular lymph node metastasis) (3) Resectable liver metastases: 2 to 5 metastatic lesions, total diameter >5 cm and ≤8 cm, tumor invades the vena cava or portal vein (4) Lung metastases (5) Isolated peritoneal implantation

4. Have received chemotherapy, immune checkpoint inhibitors, and fruquintinib for at least 2 cycles. For the neoadjuvant therapy cohort, patients who have not previously received anticancer treatment (radiotherapy, chemotherapy, targeted therapy, or immunotherapy, etc.). The patients are eligible for inclusion in the analysis set if they have received fruquintinib treatment for at least 2 cycles and have undergone at least one baseline tumor assessment. All patients included in the efficacy analysis are included in the safety analysis set.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 before treatment.

6. Expected survival time of >6 months before neoadjuvant therapy and >3 months before conversion therapy.

7. No significant organ dysfunction or drug contraindications before receiving neoadjuvant or conversion therapy.

8. There is no mandatory requirement for target lesions. Objective response rate (ORR) assessment is based on all evaluable patients, regardless of the presence of target lesions. For patients without target lesions, those assessed as non PR/non PD will be analyzed as stable disease (SD).

Exclusion Criteria:

Patients meeting any of the following criteria are not eligible to enter the study:

1. History of other primary malignant tumors, except: (1) complete remission of malignant tumors at least 2 years before enrollment and no need for other treatment during the study period; (2) adequately treated non-melanoma skin cancer or malignant melanoma without evidence of disease recurrence; (3) adequately treated in situ carcinoma.
2. Conversion therapy cohort: Diagnosis of HER2-positive gastric or gastroesophageal junction adenocarcinoma.
3. Conversion therapy cohort: Evidence of distant metastases beyond oligometastases as defined in the inclusion criteria before the first dose of study treatment (such as brain, bone, etc.).
4. Female patients who are pregnant or lactating.
5. Known allergy (Grade 3 or higher allergic reaction) or contraindication to anti-angiogenic drugs, any monoclonal antibody, or chemotherapy drug components.
6. Use of non-study drug treatments during the study period that may interfere with the analysis.
7. Patients who did not undergo any tumor efficacy assessment after receiving neoadjuvant or conversion therapy.
8. Less than 2 cycles of fruquintinib neoadjuvant or conversion therapy.
9. Patients with insufficient follow-up information as judged by the investigator (such as not returning to the hospital for treatment or efficacy assessment after initial treatment).

Histologically confirmed gastric or gastroesophageal junction adenocarcinoma. For neoadjuvant therapy cohort: candidates for Initial potentially curative surgery with cII, cIII, or cIVA stage disease (>cT2N0-3M0 or cT0-4N+M0); no distant metastasis. For conversion therapy cohort: patients with locally advanced unresectable or stage IV metastatic disease (per AJCC 8th edition).