{
  "abstract": "IMPORTANCEA recent meta-analysis showed that chemoimmunotherapy was associated with improved overall survival (OS) compared with immune checkpoint inhibitor (ICI) monotherapy for programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) [≥] 50% advanced non-small-cell lung cancer (NSCLC). However, whether this benefit reflects chemotherapy effect or ICI heterogeneity remains unclear.\n\nOBJECTIVETo reassess the survival benefit of adding chemotherapy to ICI monotherapy using agent-stratified comparisons anchored to chemotherapy.\n\nDATA SOURCESThe 24 phase 3 randomized clinical trials included in the original meta-analysis (search date, August 3, 2025).\n\nDATA EXTRACTION AND SYNTHESISHazard ratios (HRs) for OS and progression-free survival (PFS) were extracted from each trial in the original meta-analysis. Two analytic frameworks were used: within-agent comparisons (same ICI in both chemoimmunotherapy and monotherapy) and across-agent comparisons (ICI in one treatment strategy only). For within-agent comparisons, a two-stage random-effects meta-analysis was conducted. In stage 1, ICI-specific HRs for chemoimmunotherapy and ICI monotherapy versus chemotherapy were pooled and their ratio was calculated (RHR = HRchemoimmuno/HRmono; RHR < 1 favors chemoimmunotherapy). The RHRs were pooled in stage 2. For across-agent comparisons, RHR was derived from pooled HRs by treatment strategy.\n\nMAIN OUTCOMES AND MEASURESEndpoints were OS and PFS.\n\nRESULTSIn within-agent comparisons (4 ICIs; 13 trials; N = 3252), pooled RHR was 0.94 (95% CI, 0.78-1.13; P = .48; I{superscript 2} = 0.0%) for OS and 0.85 (95% CI, 0.68-1.06; P = .14; I{superscript 2} = 0.0%) for PFS. In across-agent comparisons (7 ICIs; 11 trials; N = 2231), RHR favored chemoimmunotherapy for OS (0.68; 95% CI, 0.50-0.92; P = .01) and PFS (0.46; 95% CI, 0.37-0.58; P < .001). In a sensitivity analysis restricted to trials of NCCN-recommended regimens, pooled RHR was 1.02 (95% CI, 0.81-1.28; P = .87) for OS.\n\nCONCLUSIONS AND RELEVANCEIn the within-agent comparisons, adding chemotherapy to ICI monotherapy did not improve OS or PFS in patients with PD-L1 TPS [≥] 50% advanced NSCLC. The benefit in the original meta-analysis appears driven by across-ICI heterogeneity. These findings are consistent with ICI monotherapy as a standard first-line option and underscore the need for agent-level stratification in across-trial comparisons.",
  "abstract_shown": true,
  "affiliations": [
    "The First Hospital of Jilin University"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "F. Han"
    },
    {
      "name": "J. Wang"
    },
    {
      "name": "S. Shi"
    },
    {
      "name": "M. Jin"
    },
    {
      "name": "C. Ren"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e13hfnbxqe4ab.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.26361919",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.01.26361919v1.full",
  "id": "e13hfnbxqe4ab",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.01.26361919v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "oncology"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7208788141",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.01.26361919v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e13hfnbxqe4ab.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.64898/2026.09.01.26361919",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.01.26361919v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:oncology",
      "subfield": "oncology"
    }
  ],
  "title": "No Overall Survival Benefit with Adding Chemotherapy to Immunotherapy in PD-L1 TPS >= 50% NSCLC: An Agent-Stratified Reassessment",
  "title_text": "No Overall Survival Benefit with Adding Chemotherapy to Immunotherapy in PD-L1 TPS >= 50% NSCLC: An Agent-Stratified Reassessment",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/e13hfnbxqe4ab",
  "venue": "medRxiv",
  "versions": []
}