Trial reportEsophagus : official journal of the Japan Esophageal Society2023
First-line nivolumab plus ipilimumab or chemotherapy versus chemotherapy alone in advanced esophageal squamous cell carcinoma: a Japanese subgroup analysis of open-label, phase 3 trial (CheckMate 648/ONO-4538-50).
Trial report in Esophagus : official journal of the Japan Esophageal Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03143153 (A Randomized Phase 3 Study of Nivolumab Plus Ipilimumab or Nivolumab Combined With Fluorouracil Plus Cisplatin Versus Fluorouracil Plus Cisplatin in Subjects With Unresectable Advanced, Recurrent or Metastatic Previously Untreated Esophageal Squamous Cell Carcinoma), which is not on this map. Cited by 52 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized Phase 3 Study of Nivolumab Plus Ipilimumab or Nivolumab Combined With Fluorouracil Plus Cisplatin Versus Fluorouracil Plus Cisplatin in Subjects With Unresectable Advanced, Recurrent or Metastatic Previously Untreated Esophageal Squamous Cell Carcinoma
Who cites it
52 citing papers in PubMed, 4 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- Application of chemotherapy combined with immunotherapy in first-line treatment of advanced esophageal cancer: fluorouracil or paclitaxel? - a meta-analysis.Frontiers in oncology · 2025Pooled it
- Efficacy and safety of PD-1/PD-L1 inhibitors as first-line treatment for esophageal squamous cell carcinoma: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Efficacy and safety of nivolumab plus ipilimumab in gastrointestinal cancers: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- Efficacy and safety of PD-1/PD-L1 inhibitor combined with chemotherapy versus chemotherapy alone in the treatment of advanced gastric or gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- Tislelizumab for consolidation therapy in patients with pathologically residual Esophageal Squamous Cell Carcinoma after definitive concurrent Chemoradiotherapy: a multicenter, randomized, controlled phase II trial.Future oncology (London, England) · 2024Trial
- First-line pembrolizumab plus chemotherapy for advanced/metastatic esophageal cancer: 1-year extended follow-up in the Japanese subgroup of the phase 3 KEYNOTE-590 study.Esophagus : official journal of the Japan Esophageal Society · 2024Trial
- First-line nivolumab plus ipilimumab in metastatic non-small cell lung cancer: 5-year outcomes in Japanese patients from CheckMate 227 Part 1.International journal of clinical oncology · 2023Trial
- Cost-effectiveness analysis of sugemalimab plus chemotherapy for the first-line treatment of advanced gastric cancer or gastroesophageal junction cancer.Human vaccines & immunotherapeutics · 2026Article
- First-line systemic therapy for advanced or metastatic esophageal squamous cell carcinoma: clinical implications for treatment selection after KEYNOTE-590, CheckMate 648, and RATIONALE-306.Clinical journal of gastroenterology · 2026Review
- High Serum IgA Identifies Poor Responders to Immune Checkpoint Inhibitors in Patients with Unresectable Esophageal Squamous Cell Carcinoma.Annals of surgical oncology · 2026Article
- Early Tumor Shrinkage and Clinical Outcomes for Esophageal Squamous Cell Carcinoma Patients Treated with Immune Checkpoint Inhibitors: Real-World Observational Study.Annals of surgical oncology · 2026Observational
- FOLFOX in Esophageal Squamous Cell Carcinoma: Current Evidence and Future Role as a Cisplatin-Sparing Chemoimmunotherapy Backbone.Journal of gastrointestinal cancer · 2026Review
- Article
- Real-world outcomes of ipilimumab plus nivolumab in esophageal squamous cell carcinoma: a multi-institutional large cohort study.Cancer immunology, immunotherapy : CII · 2026Article
- Prognostic Biomarkers and Immunotherapeutic Insights of Circulating Tumor DNA Analysis in Advanced Esophageal Squamous Cell Carcinoma From SCRUM-MONSTAR GOZILA Substudy.JCO precision oncology · 2026Article
- On Window Mean Survival Time With Interval-Censored Data.Statistics in medicine · 2026Article
- Article
- Subgroup-specific predictive biomarkers in peripheral blood lymphocyte subsets for immune checkpoint inhibitor response in advanced esophageal squamous cell carcinoma: a prospective study.Journal of thoracic disease · 2026Article
- Efficacy and Safety of Anti-PD-(L)1 Treatments: A Systematic Review and Meta-Analysis of Asian vs Non-Asian Patients with Esophageal Squamous Cell Carcinoma.Gastro hep advances · 2026Review
- Immunosuppressive tumor microenvironment and immunotherapy resistance of esophageal carcinoma.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 14 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProgrammed cell death 1 (PD-1)-based treatments are approved for several cancers. CheckMate 648, a global, phase 3 trial, showed that first-line nivolumab (anti-PD-1 antibody) plus ipilimumab (NIVO + IPI) or nivolumab plus chemotherapy (NIVO + Chemo) significantly increased survival in advanced esophageal squamous cell carcinoma (ESCC) without new safety signals versus chemotherapy alone (Chemo).
methodsWe evaluated the Japanese subpopulation of CheckMate 648 (n = 394/970), randomized to receive first-line NIVO + IPI, NIVO + Chemo, or Chemo. Efficacy endpoints included overall survival (OS) and progression-free survival assessed by blinded independent central review in Japanese patients with tumor-cell programmed death-ligand 1 (PD-L1) expression ≥ 1% and in all randomized Japanese patients.
resultsIn the Japanese population, 131, 126, and 137 patients were treated with NIVO + IPI, NIVO + Chemo, and Chemo, and 66, 62, and 65 patients had tumor-cell PD-L1 ≥ 1%, respectively. In patients with tumor-cell PD-L1 ≥ 1%, median OS was numerically longer with NIVO + IPI (20.2 months; hazard ratio [95% CI], 0.46 [0.30-0.71]) and NIVO + Chemo (17.3 months; 0.53 [0.35-0.82]) versus Chemo (9.0 months). In all randomized patients, median OS was numerically longer with NIVO + IPI (17.6 months; 0.68 [0.51-0.92]) and NIVO + Chemo (15.5 months; 0.73 [0.54-0.99]) versus Chemo (11.0 months). Grade 3-4 treatment-related adverse events were reported in 37%, 49%, and 36% of all patients in the NIVO + IPI, NIVO + Chemo, and Chemo arms, respectively.
conclusionSurvival benefits with acceptable tolerability observed for NIVO + IPI and NIVO + Chemo treatments strongly support their use as a new standard first-line treatment in Japanese patients with advanced ESCC. CLINICALTRIALS: GOV ID: NCT03143153.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.