The overall incidence of liver metastases from gastric cancer is about 9.9%-18.7%. Gastric cancer has strong heterogeneity and rapid disease progression, and the prognosis of liver metastasis is poor. The 5-year survival rate of patients with liver metastases from gastric cancer is very low, making clinical treatment challenging.

Thalidomide has immunomodulatory and anti-angiogenesis effects. It has been used in the treatment of multiple myeloma for more than 20 years, and there are many clinical studies in solid tumors. In recent years, thalidomide has been found to induce the degradation of IKAROS family transcription factors IKZF1 and IKZF3 in combination with CRBN. Therefore, it is very meaningful to explore the therapeutic value of thalidomide in advanced gastric cancer liver metastasis.

The overall incidence of liver metastases from gastric cancer is about 9.9%-18.7%. Gastric cancer has strong heterogeneity and rapid disease progression, and the prognosis of liver metastasis is poor. The 5-year survival rate of patients with liver metastases from gastric cancer is very low, making clinical treatment challenging. Although immune checkpoint inhibitors have been approved for third-line treatment of advanced gastric cancer, they are expensive and poorly accessible. For patients with poor economic conditions, combination therapy based on chemotherapy regimen or treatment regimen optimization may still be a relatively important direction.

Thalidomide has immunomodulatory and anti-angiogenesis effects. It has been used in the treatment of multiple myeloma for more than 20 years, and there are many clinical studies in solid tumors. In recent years, thalidomide has been found to induce the degradation of IKAROS family transcription factors IKZF1 and IKZF3 in combination with CRBN.

In addition, the sedative effect of thalidomide helps to improve patients' sleep. Thalidomide can also inhibit inflammatory factors such as TNF-α, thus improving appetite and increasing lean body weight in patients with cachexia. Its antiemetic effects can reduce gastrointestinal reactions to chemotherapeutic drugs in combined therapy. Thalidomide is also very cheap in China, which is suitable for patients on long-term maintenance treatment. Therefore, it is of great significance to explore the therapeutic value of thalidomide in liver metastasis of advanced gastric cancer.

Inclusion Criteria:

1. Aged 18-75 years old;
2. ECOG physical status score 0-1 points (within 3 days before starting treatment);
3. Expected survival period ≥ 3 months;
4. Basically normal functions of major organs;
5. Pathologically confirmed metastatic gastric cancer or adenocarcinoma at the gastroesophageal junction with no chance of radical surgery, accompanied by liver metastasis or simple liver metastasis;
6. No previous medical treatment; If neoadjuvant or adjuvant chemotherapy has been performed before and after surgery, recurrence can be defined as first-line therapy only after drug withdrawal for at least six months;
7. HER2 negative. HER2 negative definition: IHC (0 or 1+), or IHC (2+) but negative for FISH (HER2:CEP17<2 with mean HER2 copy number <4.0 signals/cell);
8. Measurable lesions assessed according to RECIST1.1;
9. Able to swallow pills normally.

Exclusion Criteria:

1. Those who are allergic to thalidomide;
2. Pregnant or lactating women;
3. Severe mental illness;
4. Those who cannot take medication or follow up as planned;
5. During the trial period and within 3 months after the trial, the subjects and their partners are not willing to use contraception;
6. Participants in other clinical studies 3 months prior to the trial；
7. Patients who are financially well off and willing to use immune checkpoint inhibitors.