Association between reactive cutaneous capillary endothelial proliferation and the efficacy of camrelizumab in esophageal cancer: a retrospective cohort study

Abstract

Background: Reactive cutaneous capillary endothelial proliferation (RCCEP) is a common immune-related adverse event (irAE) related to camrelizumab. This study sought to investigate the relationship between RCCEP and the treatment efficacy of camrelizumab in esophageal cancer (EC), and to explore the risk factors for RCCEP.

Methods: This retrospective study collected the data of patients with EC who were treated with camrelizumab between November 2019 and November 2023. The patients were divided into RCCEP-negative groups and RCCEP-positive groups based on the occurrence of RCCEP. Subsequently, the Chi-squared test was applied to analyze the differences in objective response rate (ORR) and disease control rate (DCR) between the two groups. The association between progression-free survival (PFS) or overall survival (OS), and RCCEP was analyzed by the log-rank test. The factors associated with RCCEP were analyzed using univariable and multivariable Logistic regression analyses. Data cutoff was on February 2, 2024.

Results: In total, 397 patients were included in this study, of whom 128 (32.24%) suffered from RCCEP. There were no significant differences in the baseline characteristics of the patients in the RCCEP-negative and RCCEP-positive groups. Among the patients with RCCEP, seven had grade 3 RCCEP, and none had grade 4 or 5 RCCEP. Compared with the patients without RCCEP, those with RCCEP had a significantly higher ORR (71.09% vs. 43.87%, P<0.001) and DCR (94.53% vs. 72.49%, P<0.001). In the multivariate Cox analysis, RCCEP was found to be independently associated with longer PFS (P<0.001) and OS (P<0.001). In the univariate Cox analysis of patients with RCCEP, neither RCCEP time nor grade was associated with prolonged PFS and OS. The multivariable logistic regression analysis revealed that more camrelizumab treatment cycles was significantly associated with a higher risk of RCCEP [odds ratio (OR) =1.24; 95% confidence interval (CI): 1.16-1.31] and camrelizumab combined with antiangiogenic therapy was significantly associated with a lower risk of RCCEP (OR =0.24; 95% CI: 0.07-0.86).

Conclusions: In the EC patients treated with camrelizumab, those with RCCEP had significantly better outcomes in terms of the ORR, DCR, PFS, and OS than those without RCCEP. The emergence of RCCEP may serve as a potential predictor for the therapeutic efficacy of camrelizumab in the treatment of EC. More camrelizumab treatment cycles and not receiving combined anti-angiogenic therapy were independent risk factors for RCCEP.

Keywords: Camrelizumab; esophageal cancer (EC); immune-related adverse events (irAEs); reactive cutaneous capillary endothelial proliferation (RCCEP).

Figure 1

Number of patients by treatment cycles.

Figure 2

Number of patients with (A) RCCEP and (B) irAEs by onset time. irAEs, immune-related adverse events; RCCEP, reactive cutaneous capillary endothelial proliferation.

Figure 3

PFS and OS after the camrelizumab treatment using the Kaplan-Meier method. Kaplan-Meier curves for the (A) PFS and (B) OS of all patients; the (C) PFS and (D) OS of patients with or without RCCEP; the (E) PFS and (F) OS of patients without irAEs, with irAEs but without RCCEP, and with RCCEP. CI, confidence interval; irAEs, immune-related adverse events; OS, overall survival; PFS, progression-free survival; RCCEP, reactive cutaneous capillary endothelial proliferation.