The Association of Clinical Outcomes with Posttreatment Changes in the Relative Eosinophil Counts and Neutrophil-to-Eosinophil Ratio in Patients with Advanced Urothelial Carcinoma Treated with Pembrolizumab

Abstract

Background To evaluate the association of clinical outcomes with posttreatment changes in the relative eosinophil count (REC) and neutrophil-to-eosinophil ratio (NER) in patients with advanced urothelial cancer (UC) treated with pembrolizumab. Materials and Methods We retrospectively analyzed 105 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The REC and NER before and three weeks after pembrolizumab were recorded. A receiver operating characteristic curve was used to determine the optimal cut-off values for analyzing the risk. Results There were no significant differences in the overall survival (OS) between the REC ≥4.8% and <4.8% groups and the NER ≥13.7 and <13.7 groups before pembrolizumab (p=0.997 and 0.669, respectively). However, a significant difference in the OS was confirmed between the increased and decreased REC groups and between the decreased and increased NER groups at 3 weeks after pembrolizumab (p<0.001 and 0.002, respectively). Multivariate analyses revealed that an Eastern Cooperative Oncology Group Performance Status ≥2 (P=0.003), albumin <3.7 g/dl (p=0.002), LDH >246 U/L (p=0.011), disease site ≥3 organs (p=0.019), decreased posttreatment REC (3 weeks later) (p=0.002) and increased posttreatment NER (3 weeks later) (p=0.022) were independent prognostic factors for a worse OS. Conclusion An increased REC and decreased NER after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.

Association Between Immune-Related Adverse Events and Efficacy and Changes in the Relative Eosinophil Count Among Patients with Advanced Urothelial Carcinoma Treated by Pembrolizumab

“… 37 Furthermore, we recently reported that an increased REC after pembrolizumab treatment was associated with superior OS in comparison to a decreased REC in advanced UC patients who received pembrolizumab therapy. 17 …”

“… 11 , 12 Furthermore, a number of clinical biomarkers of the response to ICIs have been reported for advanced UC, 13–16 and we previously reported that an increased relative eosinophil count (REC) after three weeks of pembrolizumab treatment may be associated with improved clinical outcomes. 17 However, it is still unclear whether an increased REC would cause increased numbers of irAEs or specific irAEs.…”

The Eosinophil Changes, Efficacy and Safety of Pembrolizumab in Advanced Urothelial Carcinoma Patients with an Older Age and a Poor Performance Status

“…It was also reported that the increase in REC and decrease in NER after pembrolizumab were associated with improved OS. 13 Therefore, the absence of eosinophil changes (eg, increase of REC and decrease of NER) may have also contributed to the shorter OS in the PS ≥2 group in the present study.…”

“…Similarly, patients with a poor PS are unlikely to be incorporated in clinical trials considering the safety profile. Recently, eosinophils have been highlighted as potential biomarkers and have been studied in patients with advanced UC treated with ICIs; 12 , 13 however, no studies have investigated eosinophils in older patients or patients with a poor PS.…”

“…[9][10][11] In patients with advanced UC who receive treatment with ICIs, not only the pretreatment eosinophil counts but also changes in eosinophil counts are associated with outcomes. 12,13 However, the associations between these factors and the outcomes of ICI treatment in older patients or patients with a poor PS in comparison to younger patients and patients with a good PS remain unclear.…”