Immunotherapy Combined With Chemoradiotherapy for First-line Treatment of Esophageal Squamous Cell Carcinoma:a Real-world Study From China
Immunotherapy Combined With Chemoradiotherapy for First-line Treatment of Esophageal Squamous Cell Carcinoma:a Real-world Study From China
This trial aims to assess efficacy and safety of immunotherapy combined with chemoradiotherapy for first-line treatment of esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma is a highly aggressive malignancy, with squamous cell carcinoma accounting for over 90% of esophageal cancer cases in China. According to the American Cancer Society, the 5-year survival rates vary among patients at different stages of esophageal cancer: approximately 50% for early and mid-stage cases, around 26% for locally advanced cases, and only 5% for those with distant metastasis.In recent years, immunotherapy combined with chemotherapy has emerged as the first-line standard treatment for advanced esophageal cancer, and several phase III trials of immunotherapy combined with radiotherapy are currently underway for locally advanced esophageal cancer. Despite being a novel treatment strategy for patients with locally advanced esophageal cancer, there remains a lack of sufficient evidence-based medical data supporting the use of immunotherapy combined with chemoradiotherapy.In recent years, immunotherapy combined with chemotherapy has emerged as the first-line standard treatment for advanced esophageal cancer, and several phase III trials of immunotherapy combined with radiotherapy are currently underway for locally advanced esophageal cancer. Despite being a novel treatment strategy for patients with locally advanced esophageal cancer, there remains a lack of sufficient evidence-based medical data supporting the use of immunotherapy combined with chemoradiotherapy.
Inclusion Criteria:
Voluntary participation and written signed informed consent;
Age 18-85 years old, gender is not limited;
Histologically or cytologically confirmed esophageal squamous cell carcinoma Exclusion Criteria,and patients with suspected brain or bone metastasis at the time of screening should undergo brain MRI or ECT before study enrollment;
Physical status score ECOG 0-1;
Weight > 40 kg;
Expected survival ≥ 6 months;
According to RECIST 1.1 guidelines, at least one lesion (not previously receiving radiotherapy) with a maximum diameter ≥ 10 mm as accurately measured by computed tomography (CT) or magnetic resonance imaging (MRI) at baseline (except lymph nodes, whose short axis must be ≥ 15 mm); And the lesion is suitable for repeated accurate measurement.;
No previous immunotherapy;
no serious abnormalities of haematopoietic, cardiac, pulmonary, hepatic; and renal functions and immunodeficiency (Haematology: white blood cells ≥3.5×109/L; neutrophils ≥1.5×109/L; haemoglobin ≥90g/L; platelets
≥100×109/L. Liver and kidney function: total bilirubin ≤1.5 times the upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) ≤2.5 times the upper limit of normal; creatinine ≤1.5 times the upper limit of normal; albumin ≥30 g/L. Coagulation: International Normalised Ratio (INR) or Prothrombin Time (PT) or Activated Partial Thromboplastin Time (APTT)
≤ 1.5 times ULN; if the subject is receiving anticoagulation therapy, PT or INR is acceptable as long as the PT or INR is within the range of the anticoagulant drug formulation. Echocardiographic assessment: left ventricular ejection fraction (LVEF) ≥ low limit of normal (50%). Pulmonary function FEV1 ≥70% of % of predicted value and DLCO ≥60% of % of predicted value).
The female patient has evidence of postmenopausal status, or the urine or serum pregnancy test results of the premenopausal woman are negative. Women who stop menstruating for 12 months without other medical reasons are considered menopausal.
Exclusion Criteria:
having any active autoimmune disease or a history of autoimmune disease (e.g. interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary gland inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (which can be included if hormone replacement therapy is effective), etc.), and a history of immunosuppressive drug use within 28 days, with the exception of the use of hormones for the purpose of dealing with toxicity from radiotherapy;
Previously received or are receiving other PD-1 antibody therapy or other immunotherapy targeting PD-1/PD-L1, or are currently participating in other interventional clinical studies for treatment;
Have received other anti-tumour therapy (including herbal therapy with anti-tumour effect) within 4 weeks prior to the first dose of the study; have received long-term systemic immunotherapy or hormone therapy (except physiological replacement therapy, e.g., oral thyroxine for hypothyroidism) within 4 weeks prior to the first dose of the study; and have been treated with other experimental drugs or interventional clinical studies within 4 weeks prior to the first dose of the study;
Patients with uncontrolled clinical cardiac symptoms or disease such as
(1) NYHA class II or higher heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, and (4) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
with congenital or acquired immune function defects (e.g., HIV-infected patients), active hepatitis B (HBV-DNA ≥104 copies/ml) or hepatitis C (hepatitis C antibody-positive with HCV-RNA above the lower limit of detection of the analytical method), or active tuberculosis;
Have an active infection or unexplained fever >38.5°C within 2 weeks prior to screening (at the investigator's discretion, subjects may be enrolled for fever arising from tumours);
In the judgement of the investigator, the subject has other factors that may cause him/her to be forced to terminate the study in the middle of the study, e.g., suffering from other serious illnesses (including psychiatric illnesses) that require comorbid treatment, family or social factors that may affect the safety of the subject or the collection of trial data.