Role of immunotherapy in gastroesophageal cancer with liver metastasis: A meta-analysis of phase III randomized clinical trials.

Abstract

319 Background: Recent studies have demonstrated a poor response to immunotherapy in patients with colorectal cancer with liver metastasis. The role of immune checkpoint inhibitors (ICIs) for patients with gastroesophageal (GE) cancer with liver metastasis remains unclear. Our objective was to investigate if ICIs are beneficial in patients with GE cancer with liver metastasis. Methods: We searched PubMed, Embase, ESMO, and ASCO Meeting Abstracts for phase III randomized clinical trials (RCTs) testing ICIs in metastatic/advanced GE cancer from 2017 to 2023. All phase III RCTs of metastatic GE cancer treated with ICIs that had available data on liver metastasis were analyzed. A meta-analysis was conducted on the survival outcomes (overall and progression-free survival), where hazard ratios were obtained, with 95% confidence intervals, using the standard random effects model. To assess the heterogeneity of the study outcomes, the I2 statistic was obtained. The I2 statistic represented the variability in the meta-analysis attributed to study heterogeneity. These analyses were applied to the overall cohort of studies, as well as within the liver metastasis (yes or no) sub-cohorts. All analyses were conducted in SAS v9.4 (Cary, NC) at a significance level of 0.05. Results: Seven Phase III RCTs were includedthat had available data on overall survival and/or progressive free survival in patients with liver metastasis. Of these, six were in the frontline setting and one in the later line. Overall, 6,109 patients were included. Overall survival was similar among all patients (HR 0.72 [0.67,0.77], p<0.001, I2=0.0%), patients with no liver metastasis (HR 0.73 [0.67,0.81], p<0.001, I2=0.0%), and patients with liver metastasis (HR 0.74 [0.67,0.81], p<0.001, I2=0.0%), indicating that ICIs’ benefit on OS is consistent. Progression-free survival (PFS) was also similar among all patients (HR 0.63 [0.57,0.70], p<0.001, I2=54.7%); those with no liver metastasis (HR 0.62 [0.51,0.76], p<0.001, I2=62.3%), and with liver metastasis (HR 0.66 [0.57,0.76], p<0.001, I2-0.0%). Funnel plots were used to identify a potential bias for studies included in the analysis and showed no significant sources of bias for OS and PFS. Conclusions: In this meta-analysis, ICIs were beneficial in patients with GE cancer with and without liver metastasis. However, the majority of the trials were in the frontline setting where ICIs were combined with chemotherapy. Further subgroup analyses should be performed with individual patient-level data to identify patients who respond best to ICIs.