Title: Meta-analysis of studies on the effectiveness of adding anti-PD1 antibodies to the first-line chemotherapy in advanced esophageal cancer
Abstract: Introduction : The results of six randomized control trials have been published by 2022, which evaluated the efficacy of adding PD-1 inhibitors to the first-line chemotherapy in patients with metastatic esophageal cancer. However, it still remains unclear which patients derive the most clinical benefit from combined therapy. Therefore, it is necessary to evaluate the efficacy of the combination of anti-PD1 treatment with chemotherapy in different patient subgroups. Materials and methods : We conducted a meta-analysis of randomized controlled trials in patients with stage IV esophageal cancer who received anti-PD1 drugs with different chemotherapeutic regimens in the first-line setting to select patients who benefit the most from the combined therapy. Results : Six randomized trials were included in the analysis for a total of 3,813 patients. Patients who received combination therapy had significantly longer OS (HR = 0.69, 95% CI: 0.63-0.75; p < 0.001), PFS (HR = 0.62, 95% CI: 0.56-0.69; p < 0.001), and better ORR (OR = 2.12, 95% CI: 1.85-2.42; p < 0.001) than those who received chemotherapy alone. Subgroup analyses showed no benefit of adding PD1-inhibitors to chemotherapy in patients with PD-L1 CPS <1 in terms of OS (HR = 0.58, 95 % CI: 0.31-1.1; p = 0.1) as well as in never-smokers (HR = 0.9, 95% CI: 0.67-1.23; p = 0.52). Conclusions : The addition of PD-1 inhibitors to the first-line chemotherapy in patients with metastatic esophageal cancer significantly improves treatment outcomes. Our results could not strongly suggest the selected patients' cohort which would benefit the most from the combination of PD-1 inhibitors and chemotherapy use.