Comparison of chemotherapy–immunotherapy and chemoradiation in esophageal cancer: A TriNetX real-world evidence study.

Abstract

e16116 Background: Although chemoimmunotherapy is widely used in esophageal cancer, real-world comparisons with standard chemoradiation are limited. We compared toxicity, healthcare utilization, and short- and long-term survival between chemotherapy plus immunotherapy without radiation (NCIT) and standard chemoradiation (NCRT). Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Adults with esophageal cancer treated with fluoropyrimidine- and platinum-based chemotherapy plus immune checkpoint inhibitors without radiation (NCIT) were compared with patients receiving chemoradiation without immunotherapy (NCRT). Outcomes were assessed at 90 days, 6 months, 1 year, and 2 years following treatment initiation. Propensity score matching (1:1) was performed to balance age, sex, race, ethnicity, and baseline comorbidities. Outcomes included toxicities, healthcare utilization, hospice use, and overall survival. Results: A total of 8,166 patients were identified (NCIT: n = 1,902; NCRT: n = 6,264). After propensity score matching, 1,501patients were included in each cohort. In the matched population, the mean age was 70.0 years in the NCIT cohort and 70.1 years in the NCRT cohort, with similar proportions of male patients (77.5% vs 76.8%). At 90 days, NCIT was associated with lower rates of neutropenia (17.0% vs 19.8%; p = 0.048), thrombocytopenia (8.9% vs 11.1%; p = 0.039), emergency visits (22.5% vs 25.9%; p = 0.03), and inpatient hospitalization (29.1% vs 39.1%; p < 0.001), with no difference in early mortality or hospice utilization. Immune-mediated colitis occurred more frequently with NCIT at 90 days (3.7% vs 2.2%; p = 0.017) and remained consistently higher at 6 months, 1 year, and 2 years. While reduced inpatient utilization persisted through 2 years, survival outcomes differed over time. Mortality was similar at 90 days and 6 months, borderline higher with NCIT at 1 year (39.4% vs 35.9%; p = 0.05), and significantly higher at 2 years (49.6% vs 43.6%; p = 0.001). Median overall survival was shorter with NCIT (416 vs 615 days), with increased risk of death (HR 1.22, 95% CI 1.10–1.35; log-rank p < 0.001). Conclusions: Chemotherapy–immunotherapy without radiation is associated with improved early tolerability and reduced healthcare utilization but shows inferior long-term survival compared with chemoradiation. These findings suggest a potential delayed survival disadvantage and underscore the importance of radiation-based multimodal therapy in esophageal cancer. Interpretation is limited by the lack of histologic subtype data, a key determinant of treatment selection and outcomes, underscoring the need for prospective studies that incorporate tumor histology.