Evaluation of Event-Free Survival Surrogating Overall Survival as the Endpoint in Neoadjuvant Clinical Trials of Gastroesophageal Adenocarcinoma.

BACKGROUND

Gastric cancer (GC) is one of the most common malignant cancers worldwide. The development of potential antitumor agents is being investigated and stimulates more clinical trials. Overall survival (OS) is consistently considered the primary endpoint for clinical trials on treatment effect assessment. However, finding an appropriate endpoint more sensitive and easy for trials is vital. For adjuvant chemotherapy, current evidence has shown that disease-free survival (DFS) could be a surrogate endpoint for randomized controlled trials (RCTs) with GC, but evidence for neoadjuvant chemotherapy (NCT) or chemoradiotherapy (NCRT) is inadequate. This study was designed to evaluate the possibility that event-free survival (EFS) surrogates OS in RCTs of NCT/NCRT of gastric orss gastroesophageal (GC or GEJ) adenocarcinoma patients (ADK).

METHODS

A literature search was conducted through databases including PubMed, the Cochrane Library, and Embase. References and articles from other sources were also included. A total of 8 RCTs with 2,837 patients were eventually analyzed. Hazard ratios (HRs) of OS and EFS were directly approached. The surrogacy of EFS was assessed through the correlation of determination R. We used Review Manage pooling HRs of OS and EFS at the trial level. I was used to demonstrate the heterogeneity of inclusions. Publication bias was summarized and illustrated through funnel plots. All analyses were on two sides with a setting statistical significance as p < 0.05.

RESULTS

Eight RCTs of 2,837 patients were analyzed at the trial level. The I for OS was 21% and 51% for EFS, and a fixed-effect model was used. The pooled HR of OS was 0.83 (95% CI: 0.75-0.92, p < 0.001), and that of EFS was 0.78 (95% CI: 0.71-0.86, p < 0.001). The regression correlation coefficient between EFS and OS was 0.76 (95% CI: 0.41-1.11, p = 0.002), and the coefficient of determination R = 0.826.

CONCLUSIONS

A strong correlation was observed between OS and EFS at the trial level. EFS could be a surrogate endpoint for neoadjuvant RCTs of GC and GEJ adenocarcinoma. Further studies and evidence from individual data are expected.