Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2023
Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651.
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02741570 (An Open Label, Randomized, Two Arm Phase III Study of Nivolumab in Combination With Ipilimumab Versus Extreme Study Regimen), which is not on this map. Cited by 107 papers, 13 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.
An Open Label, Randomized, Two Arm Phase III Study of Nivolumab in Combination With Ipilimumab Versus Extreme Study Regimen (Cetuximab + Cisplatin/Carboplatin + Fluorouracil) as First Line Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Who cites it
107 citing papers in PubMed, 13 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- Advancements in immunotherapy for oropharyngeal cancer: Current landscape and future prospects.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2026Pooled it
- Efficacy and safety of immunotherapy monotherapy versus combination regimens in recurrent/metastatic head and neck squamous cell carcinoma: A systematic review and meta-analysis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Pooled it
- Efficacy of first-line immune checkpoint inhibitors for recurrent/metastatic head and neck cancer: a systematic review and meta-analysis.Immunotherapy · 2026Pooled it
- Efficacy and safety of immunotherapy in head and neck tumors: a systematic review and meta-analysis of clinical outcomes and survival benefits.Frontiers in oncology · 2026Pooled it
- Exosomal MicroRNAs as novel diagnostic biomarkers in head and neck cancer: a systematic evaluation and meta-analysis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Pooled it
- Outcomes for recurrent or metastatic head and neck cancer by HPV status: a systematic review and meta-analysis.The oncologist · 2025Pooled it
- Evaluating the efficacy and safety of immune checkpoint inhibitors in first and second-line treatments for recurrent and metastatic head and neck squamous cell carcinoma: a systematic review and network meta-analysis of RCTs with a focus on PD-L1 expression.Frontiers in immunology · 2025Pooled it
- Efficacy of Immune Checkpoint Inhibitors in the Treatment for Head and Neck Cancer Patients: A Systematic Review and Network Meta-Analysis.Oncology research · 2025Pooled it
- Evaluating the efficacy and safety of nivolumab and ipilimumab combination therapy compared to nivolumab monotherapy in advanced cancers (excluding melanoma): a systemic review and meta-analysis.Journal of the Egyptian National Cancer Institute · 2024Pooled it
- Toxicity profiles of immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta-analysis.Cancer medicine · 2024Pooled it
- Efficacy and safety of immunotherapy for head and neck squamous cell carcinoma: a meta-analysis of randomized clinical trials.Frontiers in oncology · 2024Pooled it
- Efficacy and safety of immune checkpoint inhibitors in recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta-analysis of randomized clinical trials.Cancer medicine · 2023Pooled it
- Durvalumab with or without tremelimumab for patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis.Frontiers in immunology · 2023Pooled it
- OPTIM: a randomized phase II trial of nivolumab followed by nivolumab-ipilimumab or docetaxel at progression in recurrent/metastatic squamous cell carcinoma of the head and neck (OPTIM; AIO-KHT-0117).British journal of cancer · 2026Trial
- Trial
- INDUCE-3: A Randomized Phase II/III Study of First-line Feladilimab plus Pembrolizumab in Patients with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Trial
- MOVIE phase II trial of tremelimumab plus durvalumab combined with metronomic oral vinorelbine in patients with head and neck cancer.ESMO open · 2025Trial
- 4-1BBCell reports. Medicine · 2025Trial
- Depletion of Effector Regulatory T Cells Associates with Major Response to Induction Dual Immune Checkpoint Blockade.Cancer discovery · 2025Trial
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 20 institutions in 11 countries.
Funding
Abstract
purposeCheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
methodsPatients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration of response in the all randomly assigned and CPS ≥ 20 populations.
resultsAmong 947 patients randomly assigned, 38.3% had CPS ≥ 20. There were no statistically significant differences in OS with nivolumab plus ipilimumab versus EXTREME in the all randomly assigned (median: 13.9
conclusionCheckMate 651 did not meet its primary end points of OS in the all randomly assigned or CPS ≥ 20 populations. Nivolumab plus ipilimumab showed a favorable safety profile compared with EXTREME. There continues to be a need for new therapies in patients with R/M SCCHN.
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Registered trials
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.