Ant-PD-1/PD-L1 inhibitors in metastatic gastroesophageal cancers (GEC): A systematic review and meta-analysis.

Abstract

323 Background: CheckMate 649 and KEYNOTE 590 studies established the role of immune checkpoint inhibitors (ICI) in the frontline setting for unresectable, advanced, or metastatic GEC. However, many GEC patients do not benefit from ICI. The purpose of the study was to evaluate the efficacy of ICI in various subgroups of GEC patients. Methods: We searched MEDLINE/PubMed, Embase, ESMO, and ASCO Meeting Abstracts for phase II or III randomized clinical trials (RCTs) testing ICI in metastatic/advanced gastric or gastroesophageal junction or esophageal cancer. Outcome measures included overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed for histology (squamous vs. adenocarcinoma), cancer location (gastric, gastroesophageal junction, and esophageal), age (< 65 years vs. > = 65 years), race (Asians vs. non-Asians), and sex (male vs. females). Random-effects meta-analysis was conducted using the R software. Results: Fourteen RCTs were included for the final analysis with total of 9102 patients. RCTs were divided into three groups: 5 RCTs for ICI+ chemotherapy vs. chemotherapy (Group A), 9 RCTs for ICI vs. chemotherapy (Group B), and 2 RCTs for ICI vs. placebo (Group C). OS was improved in Groups A (HR 0.78, 95% CI 0.71-0.86) and B (HR 0.82, 95% CI 0.73-0.91), but the results were not statistically significant in Group C. PFS was improved in Groups A(HR 0.70 95% CI 0.63-0.78) and C(HR 0.69 95% CI 0.56-0.86) but not statistically significant in Group B. On subgroup analysis for Group A, a statistically significant difference in OS was seen across all subgroups: histology, cancer location, age, and race except gastroesophageal junction cancer (HR 0.83 95% CI 0.66-1.04) and females (HR 0.86 95%CI 0.73-1.01). In Group B, statistically significant differences were only seen in esophageal cancer (HR 0.73 95% CI 0.66-0.81), squamous histology (HR 0.74 95% CI 0.67-0.82), Asian race (HR 0.77 95% CI 0.67-0.88) and men (HR 0.84 95% CI: 0.77-0.92). Conclusions: This study shows evidence for the use of ICI+ chemotherapy in the frontline setting for the management of GEC. While comparing ICI against chemotherapy, esophageal cancer, squamous histology, and the Asian race seemed to benefit more from ICI. Similarly, males, in general, benefited more from ICI than females. We plan to present an updated analysis at the meeting, which will include pending publications of some ongoing clinical trials.