Real-World Efficacy Data and Predictive Clinical Parameters for Treatment Outcomes in Advanced Esophageal Squamous Cell Carcinoma Treated with Immune Checkpoint Inhibitors

Abstract

This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs. Materials and MethodsSixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included. ResultsThe median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male.Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS. ConclusionThe use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.

Prognostic Nutritional Index Predicts Response and Prognosis in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

“…Five observational studies reported that PNI was an independent indicator for a shortened OS in cancer patients with immunotherapy (18,19,(26)(27)(28), while PNI was not considered as a prognostic factor for OS in seven studies (20,(29)(30)(31)(32)(33)(34). Pooled analysis of all selected publications revealed that the PNI values higher than the cutoff value predicted a poor OS (pHR = 2.24, 95% CI = 1.57-3.20, Figure 2) in advanced cancer patients treated with immune checkpoint inhibitors.…”

“…Peng et al revealed that a higher level of PNI was associated with better survival outcomes in advanced non-small cell lung cancer (NSCLC) treated with ICIs (18). Kim et al identified that PNI greater than the cutoff was correlated with favorable progressivefree survival (PFS) and overall survival (OS) in advanced esophageal squamous cell cancer (ESCC) with immunotherapy (19). A study by Zaitsu et al showed that PNI was not a significant prognostic factor of immunotherapy in patients with lung cancer (20).…”

Prognostic and predictive impact of neutrophil‐to‐lymphocyte ratio and HLA‐I genotyping in advanced esophageal squamous cell carcinoma patients receiving immune checkpoint inhibitor monotherapy

“…Some key differences between our present study and previous studies on NLR in ESCC under immunotherapy should be highlighted. [18][19][20][21] First, our study reported the most comprehensive clinical outcomes, exhibiting significant differences in ORR, PFS and OS, while two of the four previous studies failed to exhibit the association between NLR (or derived NLR) with PFS, and one study did not analyze the results of OS and responses. Second, the cutoff values of NLR were different.…”

“…[14][15][16][17] However, studies on NLR in ESCC are limited. [18][19][20][21] A few studies have attempted to identify the association between NLR and survival in patients with ESCC treated with ICI-containing regimens; however, the findings are inconsistent and they all have common limitations. First, the retrospective nature limited the quality of response evaluation and follow-up, so none of these studies reported the complete panorama of responses and survivals as well as the continuous tracking of NLR at each evaluation; second, patients enrolled in these studies were treated with heterogenous therapeutic strategies, including different single-agent ICIs, dual blockade of PD-1 and CTLA-4, or ICIs combined with surgery, radiotherapy or chemotherapy.…”

“…Recently, the correlation of decreased overall survival (OS) and high neutrophil to lymphocyte ratio (NLR) has been observed in different tumors receiving ICIs 14–17 . However, studies on NLR in ESCC are limited 18–21 . A few studies have attempted to identify the association between NLR and survival in patients with ESCC treated with ICI‐containing regimens; however, the findings are inconsistent and they all have common limitations.…”