Evidence map›Paper›PMID 40055521›Full record

Trial reportNature medicine2025

Nivolumab plus chemotherapy or ipilimumab in gastroesophageal cancer: exploratory biomarker analyses of a randomized phase 3 trial.

Kohei Shitara, Yelena Y Janjigian, Jaffer Ajani, Markus Moehler, Jin Yao, Xuya Wang, Aparna Chhibber, Dimple Pandya, Lin Shen, Marcelo Garrido and 16 more

Abstract readClinical Trial, Phase IIIComparative StudyRandomized Controlled Trial
In one paragraph

Trial report in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Rethinking the Siewert classification in the era of precision oncology.Translational gastroenterology and hepatology · 2026
    Article
  12. Review
  13. Review
  14. Immune checkpoint inhibition inFrontiers in oncology · 2026
    Article
  15. Review
  16. Review
  17. Predictive value of homologous recombination-related gene mutations in survival outcomes of first-line nivolumab plus chemotherapy for gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025
    Article
  18. Article
  19. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Kohei Shitara *National Cancer Center Hospital East, Kashiwa, Japan.ORCID http://orcid.org/0000-0001-5196-3630
Yelena Y Janjigian *Memorial Sloan Kettering Cancer Center, New York, NY, USA. janjigiy@mskcc.org.ORCID http://orcid.org/0000-0002-5357-5858
Jaffer AjaniThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9946-0629
Markus MoehlerJohannes-Gutenberg University Clinic, Mainz, Germany.
Jin YaoBristol Myers Squibb, Princeton, NJ, USA.
Xuya WangBristol Myers Squibb, Princeton, NJ, USA.
Aparna ChhibberBristol Myers Squibb, Princeton, NJ, USA.
Dimple PandyaBristol Myers Squibb, Princeton, NJ, USA.
Lin ShenPeking University Cancer Hospital and Institute, Beijing, China.
Marcelo GarridoPontificia Universidad Católica-Universidad Mayor, Santiago, Chile.
Carlos GallardoFundacion Arturo Lopez Perez, Providencia, Chile.
Lucjan WyrwiczNarodowy Instytut Onkologii, Warsaw, Poland.
Kensei YamaguchiCancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Tomasz SkoczylasMedical University of Lublin, Lublin, Poland.ORCID http://orcid.org/0000-0002-1276-3828
Arinilda BragagnoliFundaçao Pio XII - Hospital de Câncer de Barretos, Barretos, Brazil.
Tianshu LiuZhongshan Hospital Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-8604-6311
Michael SchenkerSfantul Nectarie Oncology Center, Dolj, Romania.
Patricio YañezUniversidad de La Frontera, Temuco, Chile.
Ruben KowalyszynClinica Viedma SA, Viedma, Argentina.
Michalis KaramouzisNational and Kapodistrian University of Athens, Athens, Greece.
Thomas ZanderUniversity Hospital of Cologne, Cologne, Germany.
Kynan FeeneyNotre Dame University and Edith Cowan University, Murdoch, Western Australia, Australia.
Elena ElimovaPrincess Margaret Cancer Centre, Toronto, Ontario, Canada.
Parul DoshiBristol Myers Squibb, Princeton, NJ, USA.
Mingshun LiBristol Myers Squibb, Princeton, NJ, USA.
Ming LeiBristol Myers Squibb, Princeton, NJ, USA. ming.lei1@bms.com.ORCID http://orcid.org/0000-0002-1292-5911

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Michael Jason de la Cruz · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

First-line nivolumab-plus-chemotherapy demonstrated superior overall survival (OS) and progression-free survival versus chemotherapy for advanced gastroesophageal adenocarcinoma with programmed death ligand 1 combined positive score ≥ 5, meeting both primary end points of the randomized phase 3 CheckMate 649 trial. Nivolumab-plus-ipilimumab provided durable responses and higher survival rates versus chemotherapy; however, the prespecified OS significance boundary was not met. To identify biomarkers predictive of differential efficacy outcomes, post hoc exploratory analyses were performed using whole-exome sequencing and RNA sequencing. Nivolumab-based therapies demonstrated improved efficacy versus chemotherapy in hypermutated and, to a lesser degree, Epstein-Barr virus-positive tumors compared with chromosomally unstable and genomically stable tumors. Within the KRAS-altered subgroup, only patients treated with nivolumab-plus-chemotherapy demonstrated improved OS benefit versus chemotherapy. Low stroma gene expression signature scores were associated with OS benefit with nivolumab-based regimens; high regulatory T cell signatures were associated with OS benefit only with nivolumab-plus-ipilimumab. Our analyses suggest that distinct and overlapping pathways contribute to the efficacy of nivolumab-based regimens in gastroesophageal adenocarcinoma.

Indexed as

AdenocarcinomaAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorEsophageal NeoplasmsIpilimumabNivolumabStomach NeoplasmsAgedFemaleHumansMaleMiddle AgedProgression-Free SurvivalBiomarkers, TumorIpilimumabNivolumab

Identifiers

PMID40055521
PMCPMC12092258

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.