Association between immune-related adverse events and the efficacy of PD-1 inhibitors in advanced esophageal cancer

IntroductionRecent developments in immune checkpoint inhibitors (ICIs) have improved the treatment outcomes of esophageal cancer (EC); however, it may initiate immune-related adverse events (irAEs) in some patients. The ICIs' therapeutic efficacy is associated with irAEs in patients with non-small cell lung cancer or renal cell carcinoma, although this association is unknown in EC. The purpose of this study was to explore the association between irAEs and the efficacy of programmed death 1 (PD-1) inhibitors in EC patients. Patients and methodsThis study included patients with advanced EC treated with PD-1 inhibitors. The patients were divided into two groups according to the occurrence of irAEs. Afterward, the efficacy was compared between the irAE-negative and irAE-positive groups, and we analyzed the predictive factors of irAEs and survival. ResultsOverall, 295 patients were included in this study. Baseline characteristics were balanced in the irAE-negative and irAE-positive groups. In total, 143 (48.47%) patients experienced irAEs. The most frequent irAEs were anemia (49, 16.61%), hyperthyroidism (45, 15.25%), and pneumonitis (44, 14.92%). In total, 33 (11.19%) patients had grade >= 3 irAEs and pneumonitis have 15 (5.08%). No grade 5 adverse events were observed. A total of 52 (17.63%) and 91 (30.85%) patients had single and multiple irAEs, respectively. Compared with patients without irAEs, those with irAEs had significantly higher objective response rate (ORR) (37.76% vs. 25.00%, p = 0.018) and disease control rate (DCR) (92.31% vs. 83.55%, p = 0.022). Univariate Cox analyses indicated the significant association between irAEs and improved median progression-free survival (PFS) (10.27 vs. 6.2 months, p < 0.001) and overall survival (OS) (15.4 vs. 9.2 months, p < 0.001). In multivariate analyses, irAEs were independently associated with longer PFS (p = 0.011) and OS (p = 0.002). Moreover, multivariate analysis revealed that cycles > 8, radiation, as well as antiangiogenic therapy were strongly associated with irAEs development (p < 0.001, p = 0.002, and p = 0.025, respectively). ConclusionIn advanced EC, patients with irAEs showed markedly better efficacy in ORR, DCR, PFS, and OS compared with patients without irAEs.

Automated summary

This study explores the association between immune-related adverse events (irAEs) caused by PD-1 inhibitors and treatment outcomes in esophageal cancer (EC) patients. The results show that patients with irAEs have significantly better objective response rate, disease control rate, progression-free survival, and overall survival compared to those without irAEs.