Penpulimab Plus Chemotherapy With/Without Anlotinib for Patients With Advanced Esophageal Squamous Cell Carcinoma

Inclusion Criteria: 1. Patients with stage III-IV esophageal squamous cell carcinoma who are not candidates for curative treatment (excluding adenosquamous carcinoma mixed type); 2. Those who have not received systemic treatment in the past, or (new) adjuvant treatment/radical surgery/radical radiotherapy and chemotherapy have relapsed for more than 6 months; Note: Including patients with advanced or recurring non-target lesions who have progressed again after radiotherapy alone. For local lesions (non-target lesions), the time from the end of palliative treatment to the enrollment time\> 2 weeks; 3. According to the RECIST 1.1 version of the curative effect evaluation standard for solid tumors, there is at least one measurable lesion; the measurable lesion should not have received local treatment such as radiotherapy (the lesion located in the previous radiotherapy area, if it is confirmed that it has progressed, and meets RECIST1.1 Standard, target lesions can also be selected); 4. Patients between 18 and 75 years old; 5. ECOGPS score: 0\~1 points; the expected survival period is more than 3 months; 6. Tumor specimens can be provided to determine gene detection and PD-L1 expression, at least 15 white sheets (assessed by the company); provide two oral swabs; within 7 days before the medication, the first, third, and sixth at the end of the cycle, one tube of 6ml EDTA anticoagulant blood will be provided. 7. It has sufficient organ and bone marrow function, that is, it meets the following standards: (1) The standard of routine blood examination must meet: Hemoglobin content (HB) ≥90g/L (no blood transfusion within 28 days); Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Platelet count (PLT) ≥100×10\^9/L. (2) The biochemical inspection shall meet the following standards: Serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); ALT and AST≤2.5´ULN; if there is liver metastasis, ALT and AST≤5´ULN; Cr≤1.5´ULN or creatinine clearance (CCr)≥60ml/min; (Cockcroft-Gault formula) (3) The coagulation function is adequate, which is defined as the international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; 8) Women of childbearing age must take appropriate contraceptive measures from screening to 3 months after stopping the treatment, and they must be non-lactating patients. Before starting the administration, the pregnancy test is negative, or meeting one of the following criteria proves that there is no risk of pregnancy: 1. Post-menopausal is defined as amenorrhea at least 12 months after the age is greater than 50 years and all exogenous hormone replacement therapy is stopped; 2. For women younger than 50 years old, if the amenorrhea is 12 months or more after stopping all exogenous hormone treatments, and the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) are within the laboratory postmenopausal reference value range, also Can be considered post-menopausal; 3. Have received irreversible sterilization, including hysterectomy, bilateral ovariectomy or bilateral fallopian tube resection, except for bilateral tubal ligation. For men, they must agree to use appropriate methods of contraception or have been surgically sterilized during the trial period and 8 weeks after the last trial drug administration; 9) The patient voluntarily joined the study, signed an informed consent form, had good compliance, and cooperated with the follow-up. Exclusion Criteria: 1. It is known that esophageal squamous cell carcinoma tends to be completely obstructed under endoscopy and requires interventional treatment to relieve the obstruction; 2. Patients with ulcerative esophageal squamous cell carcinoma; 3. Patients who have a higher risk of bleeding or perforation due to the tumor's obvious invasion of the adjacent organs (aorta or trachea) of the esophageal lesion, or patients who have formed a fistula; 4. Patients with esophageal squamous cell carcinoma whose esophageal lesions have not been reduced after radiotherapy without surgical resection of the primary lesion; 5. Allergy to paclitaxel and cisplatin preparations or excipient ingredients; 6. Patients who have used paclitaxel or cisplatin in adjuvant chemotherapy and have relapsed or metastasized within six months; Note: Those who have relapsed or metastasized for more than six months can be included in the study; 7. Previously received anti-tumor immunotherapy (including immune checkpoint inhibitors, immune cell therapy, etc.) or anti-angiogenesis targeted therapy drugs (including antibodies and small molecule tyrosine kinase inhibitors); 8. There are many factors that affect oral medications (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), but patients who have difficulty swallowing and can drink, can take Anlotinib after dissolving the granules; 9. The burden of liver metastases accounts for more than 50% of the entire liver volume; 10. Patients with any severe and/uncontrolled diseases, including: 1. Patients with unsatisfactory blood pressure control using antihypertensive drugs (systolic blood pressure ≥150mmHg or diastolic blood pressure ≥100mmHg); patients with grade II or higher myocardial ischemia or myocardial infarction, arrhythmia (including QT interval ≥480ms); according to NYHA standards , Grade III-IV cardiac insufficiency, or cardiac color Doppler ultrasound examination reveals that the left ventricular ejection fraction (LVEF) is less than 50%; 2. Active or uncontrolled serious infection; 3. Liver diseases such as cirrhosis, decompensated liver disease, chronic active hepatitis; 4. Poor control of diabetes (fasting blood glucose (FBG)\> 10mmol/L); 5. Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein content is confirmed to be greater than 1.0g; 11. Long-term unhealed wounds or fractures; 12. Patients with esophageal squamous cell carcinoma with active bleeding within 2 months of the primary lesion; pulmonary hemorrhage with NCICTCAE grade\> grade 1 occurred within 4 weeks before enrollment; other sites with NCICTCAE grade\> grade 2 occurred within 4 weeks before enrollment Bleeding; patients with bleeding tendency (such as active peptic ulcer) or who are receiving thrombolytic or anticoagulant therapy such as warfarin, heparin or their analogues; 13. Major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks before the first dose of the study or expected major surgery during the study treatment period. 14. A history of gastrointestinal perforation and/or fistula in the 6 months before the enrollment treatment; or arteriovenous thrombotic events, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and lungs Embolizer 15. There are known symptomatic central nervous system metastases and/or cancerous meningitis; 16. Ascites with clinical significance, including any ascites that can be found on physical examination, ascites that has been treated in the past or still needs to be treated at present, only those with a small amount of ascites but asymptomatic on imaging can be selected; 17. Patients with moderate pleural effusion on both sides, or large pleural effusion on one side, or patients who have caused respiratory dysfunction and require drainage; 18. Known to have active tuberculosis; 19. Suffer from interstitial lung disease that requires steroid therapy; 20. Uncontrolled metabolic disorders or other non-malignant tumor organs or systemic diseases or cancer secondary reactions, which may lead to higher medical risks and/or uncertainty in survival evaluation; 21. Patients with significant malnutrition, BMI\<13.6kg/m2; 22. People who have a history of psychotropic drug abuse and cannot be quit or have mental disorders; 23. Have a history of immunodeficiency, including those who have tested positive for HIV or have other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 24. History of other primary malignant tumors, except for the following: 1) Malignant tumors that have been completely remitted for at least 2 years before enrollment and no other treatment is required during the study period; 2) Non-melanoma skin that has been adequately treated and has no evidence of disease recurrence Carcinoma or malignant freckle-like nevus; 3) Carcinoma in situ that has been adequately treated and has no evidence of disease recurrence; 25. Female patients who are pregnant or breastfeeding; 26. According to the judgment of the investigator, those with concomitant diseases that seriously endanger the safety of the patient or affect the patient's completion of the study.