# CheckMate 648: nivolumab combination therapy in advanced oesophageal squamous cell carcinoma

Source: https://onco.cc/key-papers/paper-checkmate-648-nejm-2022/  
OnCo record `paper-checkmate-648-nejm-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding nivolumab to chemotherapy, or combining nivolumab with ipilimumab without chemotherapy, lengthened survival compared with chemotherapy alone in advanced oesophageal squamous cell carcinoma, with the largest gains in PD-L1-positive tumours.

## Summary

Phase 3 trial of 970 patients with previously untreated advanced oesophageal squamous cell carcinoma randomised to nivolumab plus fluorouracil-cisplatin, nivolumab plus ipilimumab, or chemotherapy alone.

In tumours with PD-L1 expression of 1 percent or more, median overall survival was 15.4 months with nivolumab-chemotherapy and 13.7 months with nivolumab-ipilimumab against 9.1 months with chemotherapy (hazard ratios 0.54 and 0.64); benefit was also seen in the overall population.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2022
- DOI: 10.1056/NEJMoa2111380
- Authors: Doki Y, Ajani JA, Kato K, et al.
- Findings: PD-L1 1 percent or more: median overall survival 15.4 (nivolumab-chemotherapy) and 13.7 (nivolumab-ipilimumab) vs 9.1 months (chemotherapy).; All randomised: 13.2 and 12.7 vs 10.7 months.
- What it means: Nivolumab plus chemotherapy or nivolumab plus ipilimumab are first-line standards for advanced oesophageal squamous cell carcinoma, joining pembrolizumab-chemotherapy from KEYNOTE-590.
- Caveats: Early progression was more frequent with chemotherapy-free nivolumab-ipilimumab.; Benefit in PD-L1-negative tumours was uncertain.

## Sources

- N Engl J Med 2022: https://doi.org/10.1056/NEJMoa2111380
- PubMed: https://pubmed.ncbi.nlm.nih.gov/35108470/

## Connected records

- cancers: [Oesophageal squamous cell carcinoma](https://onco.cc/cancers/oesophageal-squamous-cell-carcinoma/)
- drugs: [Nivolumab](https://onco.cc/drugs/nivolumab/)
- trials: [CheckMate 648](https://onco.cc/trials/checkmate-648/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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