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. 2025 Sep 28;17(19):3149.
doi: 10.3390/cancers17193149.

Real-World Outcomes and Biomarker Analysis Based on Routine Clinical, Laboratory, and Pathologic Parameters in Metastatic or Unresectable Esophageal Cancer Treated with First-Line Anti-PD-1 Plus Fluoropyrimidine and Platinum

Jiyun Jeong  1 , Seyoung Seo  1 , Sung-Bae Kim  1 , Joon Seon Song  2 , Hye Ryun Kim  3 , Byoung Chul Cho  3 , Minkyu Jung  3 , Chang Gon Kim  3 , Moonki Hong  3 , Min Hee Hong  3 , Sook Ryun Park  1
Affiliations

Real-World Outcomes and Biomarker Analysis Based on Routine Clinical, Laboratory, and Pathologic Parameters in Metastatic or Unresectable Esophageal Cancer Treated with First-Line Anti-PD-1 Plus Fluoropyrimidine and Platinum

Jiyun Jeong et al. Cancers (Basel). .

Abstract

Background/objectives: The combination of anti-programmed death-1 (PD-1) inhibitors and chemotherapy is the standard first-line treatment for unresectable or metastatic esophageal squamous cell carcinoma (ESCC). However, real-world data remain limited, particularly regarding prognostic biomarkers.

Methods: This multi-institutional retrospective study analyzed patients with metastatic or unresectable ESCC who received first-line pembrolizumab or nivolumab plus fluoropyrimidine and platinum-based chemotherapy. Treatment regimens mirrored those in KEYNOTE-590 and CheckMate 648. Efficacy, safety, and prognostic factors were assessed. Prognostic factors were identified using multivariable Cox regression, and a point-based risk scoring system was developed.

Results: Among 87 patients, the objective response rate was 48.3%, and the disease control rate was 77.0%. Median progression-free survival (PFS) was 5.6 months (95% CI, 4.5-8.7), and the median overall survival (OS) was 13.1 months (95% CI, 10.6-not reached). Grade 3-4 treatment-related adverse events occurred in 51.7% of patients. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2, elevated C-reactive protein, and lower programmed death-ligand 1 (PD-L1) combined positive score (CPS) were independently associated with worse PFS and OS. A prognostic risk score ranging from 0 to 5 based on these factors stratified patients into four prognostic groups with distinct survival outcomes. Median PFS ranged from not reached in the low-risk group to 2.1 months in the high-risk group. Stratifying PD-L1 CPS into three levels (<10, 10-49, ≥50) revealed a graded association between CPS and treatment outcomes, supporting the need for more nuanced PD-L1 evaluation beyond binary classification.

Conclusions: First-line anti-PD-1 therapy combined with chemotherapy demonstrated favorable real-world outcomes in ESCC. The proposed prognostic scoring system may help personalize treatment strategies.

Keywords: anti-PD-1 immunotherapy; esophageal squamous cell carcinoma; prognostic factors; real-world evidence; risk stratifications.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow diagram of patient selection and exclusion.
Figure 2
Figure 2
Kaplan–Meier curves for the total study population. (A) progression-free survival (PFS); (B) overall survival (OS). Tick marks indicate censored observations. Dashed lines denote the median survival time where the survival probability reaches 0.5. CI, confidence interval; NR, not reached.
Figure 3
Figure 3
Kaplan–Meier curves for the total study population stratified by risk groups. (A) progression-free survival (PFS); (B) overall survival (OS). Risk groups were defined as follows: low-risk (score 0), intermediate–low-risk (score 1), intermediate–high-risk (score 2), and high-risk (score 3–5). p values were calculated using the log-rank test. Tick marks indicate censored observations. Dashed lines denote the median survival time where the survival probability reaches .0.5. CI, confidence interval; NR, not reached.
See this image and copyright information in PMC

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