PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous-cell cancer treated with chemotherapy alone
Background: Programmed death-ligand 1 (PD-L1) expression is a well-established positive predictive biomarker for response to immunotherapy in advanced esophageal squamous-cell carcinoma (aESCC). However, the association between PD-L1 and response to chemotherapy alone remains unclear. This study aim...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | ESMO Gastrointestinal Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949819824000700 |
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| author | M. Sachdeva J.J. Zhao K.X. Zhu D.T.W. Yap N.Z.H. Wong N.B. Kumarakulasinghe J. Tey R. Sundar |
| author_facet | M. Sachdeva J.J. Zhao K.X. Zhu D.T.W. Yap N.Z.H. Wong N.B. Kumarakulasinghe J. Tey R. Sundar |
| author_sort | M. Sachdeva |
| collection | DOAJ |
| description | Background: Programmed death-ligand 1 (PD-L1) expression is a well-established positive predictive biomarker for response to immunotherapy in advanced esophageal squamous-cell carcinoma (aESCC). However, the association between PD-L1 and response to chemotherapy alone remains unclear. This study aims to determine the prognostic significance of PD-L1 expression in patients treated with first-line chemotherapy alone in aESCC. Materials and methods: First-line phase III randomized trials that included PD-L1 expression as a biomarker in aESCC were extracted after a systematic search. A graphical reconstructive algorithm was used to estimate time-to-event outcomes from reported Kaplan–Meier (KM) plots and, where unavailable, KMSubtraction was utilized to derive KM plots of unreported PD-L1 subgroups. Thereafter, an individual patient data meta-analysis was conducted. Survival analyses for overall survival (OS) and progression-free survival (PFS) were conducted with Cox proportional hazards models with a shared-frailty term incorporated to account for interstudy differences. Results: Chemotherapy arms from five randomized phase III trials—CheckMate-648, ESCORT-1st, KEYNOTE-590, RATIONALE-306 and ORIENT-15—comprising 1517 patients were included in the OS analysis. Compared with PD-L1-low-expressing tumors, patients with PD-L1-high-expressing tumors were at a significantly higher risk of mortality [hazard ratio (HR) 1.153, 95% confidence interval (CI) 1.018-1.305, P = 0.025]. Three trials—CheckMate-648, ESCORT-1st and ORIENT-15—comprising 949 patients treated with chemotherapy alone were included in the PFS analysis. Patients with PD-L1-high-expressing tumors had a non-significant increased risk of tumor progression (HR 1.076, 95% CI 0.923 –1.253, P = 0.349). Conclusions: Our study found PD-L1 expression is a negative predictor of OS in aESCC treated with first-line chemotherapy. |
| format | Article |
| id | doaj-art-4b1fa53ef7af42ecac7d6f9d2e943749 |
| institution | DOAJ |
| issn | 2949-8198 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | ESMO Gastrointestinal Oncology |
| spelling | doaj-art-4b1fa53ef7af42ecac7d6f9d2e9437492025-08-20T02:50:30ZengElsevierESMO Gastrointestinal Oncology2949-81982025-03-01710010910.1016/j.esmogo.2024.100109PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous-cell cancer treated with chemotherapy aloneM. Sachdeva0J.J. Zhao1K.X. Zhu2D.T.W. Yap3N.Z.H. Wong4N.B. Kumarakulasinghe5J. Tey6R. Sundar7Department of Haematology-Oncology, National University Cancer Institute, National University Hospital, SingaporeDepartment of Haematology-Oncology, National University Cancer Institute, National University Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, SingaporeDepartment of Biomedical Informatics, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeYong Loo Lin School of Medicine, National University of Singapore, SingaporeYong Loo Lin School of Medicine, National University of Singapore, SingaporeYong Loo Lin School of Medicine, National University of Singapore, SingaporeDepartment of Radiation Oncology, National University Cancer Institute, National University Hospital, SingaporeDepartment of Haematology-Oncology, National University Cancer Institute, National University Hospital, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore; The N.1 Institute for Health, National University of Singapore, Singapore; Singapore Gastric Cancer Consortium, Singapore, Singapore; Correspondence to: Prof. Raghav Sundar, Department of Haematology-Oncology, National University Cancer Institute, National University Hospital, Singapore; Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore; The N.1 Institute for Health, National University of Singapore, Singapore; Singapore Gastric Cancer Consortium, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore. Tel: +65-67795555Background: Programmed death-ligand 1 (PD-L1) expression is a well-established positive predictive biomarker for response to immunotherapy in advanced esophageal squamous-cell carcinoma (aESCC). However, the association between PD-L1 and response to chemotherapy alone remains unclear. This study aims to determine the prognostic significance of PD-L1 expression in patients treated with first-line chemotherapy alone in aESCC. Materials and methods: First-line phase III randomized trials that included PD-L1 expression as a biomarker in aESCC were extracted after a systematic search. A graphical reconstructive algorithm was used to estimate time-to-event outcomes from reported Kaplan–Meier (KM) plots and, where unavailable, KMSubtraction was utilized to derive KM plots of unreported PD-L1 subgroups. Thereafter, an individual patient data meta-analysis was conducted. Survival analyses for overall survival (OS) and progression-free survival (PFS) were conducted with Cox proportional hazards models with a shared-frailty term incorporated to account for interstudy differences. Results: Chemotherapy arms from five randomized phase III trials—CheckMate-648, ESCORT-1st, KEYNOTE-590, RATIONALE-306 and ORIENT-15—comprising 1517 patients were included in the OS analysis. Compared with PD-L1-low-expressing tumors, patients with PD-L1-high-expressing tumors were at a significantly higher risk of mortality [hazard ratio (HR) 1.153, 95% confidence interval (CI) 1.018-1.305, P = 0.025]. Three trials—CheckMate-648, ESCORT-1st and ORIENT-15—comprising 949 patients treated with chemotherapy alone were included in the PFS analysis. Patients with PD-L1-high-expressing tumors had a non-significant increased risk of tumor progression (HR 1.076, 95% CI 0.923 –1.253, P = 0.349). Conclusions: Our study found PD-L1 expression is a negative predictor of OS in aESCC treated with first-line chemotherapy.http://www.sciencedirect.com/science/article/pii/S2949819824000700 |
| spellingShingle | M. Sachdeva J.J. Zhao K.X. Zhu D.T.W. Yap N.Z.H. Wong N.B. Kumarakulasinghe J. Tey R. Sundar PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous-cell cancer treated with chemotherapy alone ESMO Gastrointestinal Oncology |
| title | PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous-cell cancer treated with chemotherapy alone |
| title_full | PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous-cell cancer treated with chemotherapy alone |
| title_fullStr | PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous-cell cancer treated with chemotherapy alone |
| title_full_unstemmed | PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous-cell cancer treated with chemotherapy alone |
| title_short | PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous-cell cancer treated with chemotherapy alone |
| title_sort | pd l1 expression as a negative predictive biomarker in advanced esophageal squamous cell cancer treated with chemotherapy alone |
| url | http://www.sciencedirect.com/science/article/pii/S2949819824000700 |
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