Evidence mapPaperPMID 42444824Full record

SynthesisFrontiers in oncology2026

Impact of metastatic pattern and histologic subtype on PD-(L)1 inhibitor efficacy in HER2-negative advanced gastric and gastroesophageal cancer: a meta-analysis.

Derek Tai, Kyung-Il Kim, Pranati Shah, Daniel Park, Lucas Kim, Jianan Li, Claire Jung, Sofia Guzman, Gagandeep Brar, Shengyang Wu and 1 more

Abstract readSystematic Review
In one paragraph

Synthesis in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Derek Tai *Department of Internal Medicine, Loma Linda University Medical Center, Loma Linda, CA, United States.
Kyung-Il Kim *Department of Internal Medicine, Kaiser Permanente Fontana Medical Center, Fontana, CA, United States.
Pranati ShahDepartment of Internal Medicine, Loma Linda University Medical Center, Loma Linda, CA, United States.
Daniel ParkDepartment of Hematology and Oncology, Harbor-University of California, Los Angeles (UCLA) Medical Center, Torrance, CA, United States.
Lucas KimSchool of Medicine, Loma Linda University, Loma Linda, CA, United States.
Jianan LiFaculty of Kinesiology & Physical Education, University of Toronto, Toronto, ON, Canada.
Claire JungFlintridge Preparatory School, La Cañada Flintridge, CA, United States.
Sofia GuzmanDepartment of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, United States.
Gagandeep BrarDepartment of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, United States.
Shengyang WuRadiation Oncology/Gamma Knife, Valley/Mt Sinai Comprehensive Cancer Center, Paramus, NJ, United States.
Dani CastilloDepartment of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: The therapeutic benefit of PD-(L)1 blockade in advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJ) may vary by niche and tumor biology. We conducted a meta-analysis to evaluate how metastatic site and Lauren histologic subtype influence survival outcomes in HER2-negative GC/GEJ treated with PD-(L)1 inhibitor-based chemoimmunotherapy. Methods: A systematic PubMed, MEDLINE, and Embase search identified phase III randomized controlled trials published between 2021 and 2025 comparing IO plus platinum-fluoropyrimidine chemotherapy vs. chemotherapy alone in HER2-negative metastatic or unresectable GC/GEJ. Hazard ratios (HRs) for overall survival (OS) were pooled using random-effects models in the intention-to-treat (ITT) population and prespecified subgroups, including liver metastases (LM), peritoneal metastases (PM), Lauren histologic subtype, and PD-L1 expression assessed by combined positive score (CPS) or tumor area positivity score (TAPS). Between-study heterogeneity was assessed using the I² statistic, and analyses were conducted in R. Results: Six global trials including 5, 410 patients (CHECKMATE 649, ATTRACTION-4, KEYNOTE-859, ORIENT-16, RATIONALE-305, AND GEMSTONE-303) were analyzed. Overall, IO plus CT significantly improved OS compared with CT alone (HR 0.79, 95% CI 0.75-0.84; p<0.001). Survival benefit was observed in patients with and without LM (HR 0.75 and 0.82), whereas patients with PM derived limited benefit (HR 0.93). Intestinal-type tumors achieved greater OS improvement than diffuse-type tumors (HR 0.78 vs 0.87). PD-L1 CPS ≥5 predicted superior OS benefit (HR 0.70). Grade ≥3 adverse events were infrequent and hematologic. Conclusion: First-line chemoimmunotherapy prolongs survival in HER2-negative GC/GEJ. Reduced benefit in diffuse-type and peritoneal disease underscores heterogeneity and supports site- and histology-specific strategies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251174893.

Indexed as

gastric cancergastroesophageal junctionimmunotherapyLauren classificationmetastatic sitePD-1 blockade

Identifiers

PMID42444824
PMCPMC13357174

What Socratic holds

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Registered trials

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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 Socratic graph.