Effects of Immunotherapy on Quality-of-Life Outcomes in Patients with Gastroesophageal Cancers: A Meta-Analysis of Randomized Controlled Trials

Abstract

Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer care, with increasing data demonstrating improved survival outcomes using ICIs among patients with advanced gastroesophageal cancer (GEC). ICIs are also associated with a lower incidence of grade ≥ 3 adverse events (AEs) compared to chemotherapy, suggesting that ICIs may have favorable effects on health-related quality of life (HRQoL). This meta-analysis sought to evaluate the effects of ICIs on the HRQoL of patients with advanced GEC. Methods We conducted an online bibliographic search on Medline via PubMed using MeSH-based terms to retrieve randomized controlled trials (RCTs) that evaluated the effects of ICIs on HRQoL in patients with advanced GEC (we searched for all studies between 2018–2021). We included RCTs that incorporated ICIs as part of the intervention arm either as monotherapy (first- or second-line) or as a combination therapy (first-line) with another ICI or chemotherapy. We combined the HRQoL measures into a meta-analysis using standard random effects models, from which estimates of the average mean difference (MD) were obtained with 95% confidence intervals. We assessed heterogeneity of the study outcomes using the Q and I2 statistics. Results We identified 11 phase-3 RCTs that met inclusion criteria, with a mean enrollment of 820 patients. Eight RCTs had ICI plus chemotherapy combination in the intervention arm, three had ICIs as monotherapy, and one had doublet ICI therapy in the intervention arm. All RCTs had chemotherapy for the control arm. Collectively, trials reported 37 HRQoL measures using 5 different HRQoL tools. The pooled analysis favored the intervention over the control arm in terms of Functional Assessment of Cancer Therapy-Esophageal (FACT-E) scores [MD 2.7 (95% CI 0.1 to 5.3), p < 0.041]. In a subgroup analysis of eight RCTs comparing combination therapy with ICIs plus chemotherapy versus chemotherapy alone, the effect estimates favored the ICI arm regarding the FACT-E [MD 2.7 (95% CI 0.1 to 5.3), p < 0.041] and the EORTC QLQ-OES18 pain scale [MD -2.2 (95% CI -4.3 to -0.2), p < 0.030]. Likewise, the effect estimates favored ICIs monotherapy arm over chemotherapy alone regarding QLQ-STO22 hair loss subscale [MD -23.2 (95% CI -29.7 to -16.7), p < 0.001], QLQ-STO22 dysphagia subscale [MD 6.7 (95% CI 1.7 to 11.7), p = 0.009], EQ-5D pain scale [MD 6.9 (95% CI 2.9 to 10.9), p < 0.001], and QLQ-OES18 saliva subscale [MD 5.8 (95% CI 0.1 to 11.6), p = 0.046]. Conclusions In this meta-analysis, we found that the inclusion of ICIs for advanced GEC yielded better HRQoL outcomes than chemotherapy alone. Further research on the impact of ICIs on HRQoL is needed, with increasing evidence that ICIs improve survival outcomes in patients with advanced GEC.