Effects of immune checkpoint inhibitor on the quality of life of patients with advanced/metastatic esophageal, gastro-esophageal junction, and gastric cancers: A systematic review of randomized controlled trials.

e16351 Background: Immune checkpoint inhibitors (ICIs) have demonstrated survival benefits in patients with advanced or metastatic upper gastrointestinal cancers; however, their impact on patient-reported quality of life (QoL) remains poorly characterized. This systematic review aims to evaluate the effect of ICIs on QoL outcomes in patients with advanced or metastatic gastric/gastro-esophageal junction cancer (GC/GEJC) or esophageal cancer (EC). Methods: PubMed, Scopus, and Cochrane databases were systematically searched for publications up to 18 January 2025 to identify randomized controlled trials (RCTs) reporting QoL outcomes in patients with GC/GEJC or EC receiving ICIs. QoL were assessed using the EORTC QLQ-C30, QLQ-OES18 and the EQ-5D visual analogue scale (VAS). Outcomes were pooled using random-effects meta-analyses, using mean differences (MDs) for change-from-baseline outcomes and hazard ratios (HRs) for time-to-deterioration outcomes. Results: Eleven RCTs including 6392 unique patients were analyzed (7 RCTs including 2060 patients with EC and 5 RCTs including 4332 patients with GC/GEJC). Pembrolizumab was evaluated in six RCTs, tislelizumab in 4, and nivolumab in 1. Compared with chemotherapy, ICIs did not worsen cancer-specific QoL (QLQ-C30/GHS: MD 0.55 [95%CI-1.65 to 2.75]; I2= 57%, p = 0.030) or general health status (EQ-5D VAS: 0.16 [-1.04 to 1.36]; I2= 0%, p = 0.690). Moreover, ICIs were not associated with earlier deterioration in global health status (HR 0.91 [0.80 to 1.03]; I2= 0%, p = 0.911) or physical functioning (0.88 [0.76 to 1.01]; I2= 1%, p = 0.363). No significant differences were observed for esophageal-specific symptoms, including dysphagia (1.03 [0.69 to 1.53]; I2= 74%, p = 0.021), reflux (1.01 [0.55 to 1.84]; I2= 87%, p < 0.001), appetite loss (0.99 [0.85 to 1.16]; I2= 0%, p = 0.642), nausea/vomiting (0.80 [0.59 to 1.08]; I2= 64%, p = 0.062), and pain (0.93 [0.81 to 1.08]; I2= 0%, p = 0.470). Conclusions: These findings support the tolerability of ICIs, demonstrating maintenance of health-related QoL in patients with advanced or metastatic upper gastrointestinal cancer without accelerated deterioration across functional or symptom domains.