Statistical analysis
tumor
PRIMARY TUMOR, LIVER METASTASIS, TUMOR, METASTASIS
Using the Simon’s optimal two-stage design, with the power of 80% and one-sided α of 5%, the planned sample size was 22 patients. Considering the efficacy of anti-PD-1 monoclonal antibody combined with anti-angiogenesis targeted therapy, we set the primary endpoint PFS at 5 months, and we expected that the ORR could increase from 10 to 35%. In the first stage, we enrolled 8 patients. If 1 or more patients reached an objective response, we would enroll additional 14 or more patients in the second stage. Ultimately, if 5 or more of 22 patients reached an objective response, the primary endpoint was met.Patients who completed at least one treatment cycle with at least one follow-up tumor assessment were considered evaluable for efficacy. All patients who had undergone at least one treatment cycle were included in the safety assessment. The 95% CIs of ORR and DCR were calculated using exact binomial test. Median PFS, OS and their 95% CIs, were estimated using the Kaplan–Meier method and compared using log-rank test. Hazard ratio (HR) and 95% CIs were calculated using Cox proportional hazard model. Exploratory analyses were performed between subgroups by sex, primary tumor site, ECOG performance status, pathological grade, Lauren classification, metastasis site, and liver metastasis. All statistical analyses were two-sided and significance was set at 