{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T01:54:21Z","timestamp":1793757261157,"version":"4.6.1"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:sec id=\"ab-coi220074-4\"><jats:title>Importance<\/jats:title><jats:p>Immune checkpoint inhibitors (ICIs) have improved survival outcomes of patients with advanced esophageal squamous cell carcinoma in both first- and second-line settings. However, the benefit of ICIs in patients with low programmed death ligand 1 (PD-L1) expression remains unclear.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi220074-5\"><jats:title>Objective<\/jats:title><jats:p>To derive survival data for patient subgroups with low PD-L1 expression from clinical trials comparing ICIs with chemotherapy in esophageal squamous cell carcinoma and to perform a pooled analysis.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi220074-6\"><jats:title>Data Sources<\/jats:title><jats:p>Kaplan-Meier curves from the randomized clinical trials were extracted after a systematic search of Scopus, Embase, PubMed, and Web of Science from inception until October 1, 2021.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi220074-7\"><jats:title>Study Selection<\/jats:title><jats:p>Randomized clinical trials that investigated the effectiveness of anti\u2013PD-1\u2013based regimens for advanced esophageal squamous cell carcinoma and that reported overall survival (OS), progression-free survival, or duration of response were included in this meta-analysis.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi220074-8\"><jats:title>Data Extraction and Synthesis<\/jats:title><jats:p>Kaplan-Meier curves of all-comer populations, subgroups with high PD-L1, and those with low PD-L1 (when available) were extracted from published articles. A graphic reconstructive algorithm was used to calculate time-to-event outcomes from these curves. In studies with unreported curves for subgroups with low PD-L1 expression, KMSubtraction was used to impute survival data. KMSubtraction is a workflow to derive unreported subgroup survival data with from subgroups. An individual patient data pooled analysis including previously reported and newly imputed subgroups was conducted for trials with the same treatment line and PD-L1 scoring system. Data analysis was conducted from January 1, 2022, to June 30, 2022.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi220074-9\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Primary outcomes included Kaplan-Meier curves and hazard ratios (HRs) for OS for subgroups with low PD-L1 expression. Secondary outcomes included progression-free survival and duration of response.<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi220074-10\"><jats:title>Results<\/jats:title><jats:p>The randomized clinical trials CheckMate-648, ESCORT-1st, KEYNOTE-590, ORIENT-15, KEYNOTE-181, ESCORT, RATIONALE-302, ATTRACTION-3, and ORIENT-2 were included, totaling 4752 patients. In the pooled analysis of first-line trials that evaluated a tumor proportion score (CheckMate-648 and ESCORT-1st), no significant benefit in OS was observed with immunochemotherapy compared with chemotherapy in the subgroup of patients who had a tumor proportion score lower than 1% (HR, 0.91; 95% CI, 0.74-1.12; <jats:italic>P<\/jats:italic>\u2009=\u2009.38) compared with chemotherapy. In the pooled analysis of first-line trials that evaluated combined positive score (KEYNOTE-590 and ORIENT-15), there was a significant but modest OS benefit for immunochemotherapy compared with chemotherapy in the subgroup with a combined positive score lower than 10 (HR, 0.77; 95% CI, 0.62-0.94; <jats:italic>P<\/jats:italic>\u2009=\u2009.01).<\/jats:p><\/jats:sec><jats:sec id=\"ab-coi220074-11\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Findings suggest a lack of survival benefit of ICI-based regimens in the first-line setting compared with chemotherapy alone in the subgroup with a tumor proportion score lower than 1%.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2022.5816","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T16:01:33Z","timestamp":1670515293000},"page":"215","source":"Crossref","is-referenced-by-count":94,"title":["Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell 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Seong","family":"Tey","sequence":"additional","affiliation":[{"name":"Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Department of Radiation Oncology, National University Cancer Institute, National University Hospital, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghav","family":"Sundar","sequence":"additional","affiliation":[{"name":"Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Department of Haematology-Oncology, National University Cancer Institute, National University Hospital, Singapore"},{"name":"Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore"},{"name":"The N.1 Institute for Health, National University of Singapore, Singapore"},{"name":"Singapore Gastric Cancer Consortium, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Pietrantonio","sequence":"additional","affiliation":[{"name":"Medical Oncology 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