Updated pooled analyses of first-line anti-PD1/PD-L1 inhibitors plus chemotherapy in advanced esophageal squamous cell carcinoma.

Abstract

366 Background: Advanced and metastatic esophageal squamous cell carcinoma (ESCC) patients have limited treatment options and poor prognosis. Recently, several studies demonstrated the clinical benefit of combining immune checkpoint inhibitors (ICI) and chemotherapy (CT), leading to its approval in the first-line setting. Since then, efforts have been made to identify the patients who may benefit the most or not from the combination of ICI plus CT. Methods: We searched PubMed, Scopus, and the Cochrane Library for randomized clinical trials investigating first-line ICI plus chemotherapy (CT) for advanced or metastatic ESCC patients. Outcomes of interest included: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and OS according to gender, PD-L1 expression (<1% / ≥1%), and PD-L1 CPS (<10 / ≥10). We used I2 statistics to assess heterogeneity, and the fixed-effect model was used to pool studies. Results: Eight studies were included with 4,702 patients. Of them, most had an ECOG 0 or 1, and were younger than 65 years (62%), male (77%), and Asian (78%). Metastatic disease was diagnosed in 75% of patients. ICI plus CT was administered to 58%, and 43% received CT +/- placebo. Median follow-up ranged from 7.1 to 22.6 months. ICI plus CT significantly improved all efficacy outcomes compared to CT alone: decreasing the risk of death by 32% (HR for OS: 0.68; 95%CI 0.63-0.74; p<0.00001); reducing the risk of progression or death by 38% (HR for PFS: 0.62; 95%CI 0.58-0.67; p<0.00001); and increasing the objective response rate (risk difference: 0.17; 95%CI 0.14-0.20; p<0.00001). A survival benefit was seen across all subgroup analyses, but it was significantly higher in patients with PD-L1 ≥1% compared to those with PD-L1 <1% (reduction in the risk of death of 38% versus 23% respectively, p=0.03). OS was not significantly different between males versus females, or PD-L1 CPS≥10 versus CPS<10. Conclusions: Our large systematic review and meta-analysis support the efficacy and survival benefit of ICI plus CT as first-line therapy for all ESCC patients, regardless of gender or PD-L1 expression.