{
  "abstract": "Background: Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) plus pemetrexed-platinum chemotherapy are a first-line option for advanced EGFR-mutant NSCLC. However, whether benefit varies by genomic co-alteration background remains unclear. This study evaluated whether baseline co-alteration patterns are associated with differential efficacy of combined chemotherapy versus TKI monotherapy.\n\nMethods: We retrospectively enrolled patients with advanced EGFR-mutant NSCLC receiving first-line third-generation EGFR-TKI monotherapy or combination with pemetrexed-platinum chemotherapy at two centers (2018–2025). Based on baseline NGS, patients were stratified into group A (EGFR mutation alone), group B (non-driver co-mutations), and group C (driver co-mutations). One-to-one propensity score matching (PSM) was applied. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), intracranial efficacy, and safety.\n\nResults: Overall, 848 patients were enrolled; after PSM, 285 remained in each arm. The combination arm showed numerically longer median PFS (23.3 vs. 17.3 months; HR = 0.654; P < 0.001) and OS (41.2 vs. 33.7 months; HR = 0.750; P = 0.005). Group B derived the greatest benefit (mPFS: 23.0 vs. 15.3 months, HR = 0.554, P < 0.001; mOS: 39.9 vs. 33.1 months, HR = 0.694, P = 0.007), whereas groups A (mPFS: 26.5 vs. 22.8 months, HR = 0.833, P = 0.253) and C (mPFS: 14.5 vs. 10.2 months, HR = 0.584, P = 0.088) showed no significant differences. The treatment-by-co-alteration interaction for PFS was significant (P = 0.032). Among patients with baseline brain metastases, median intracranial PFS was numerically longer with combination therapy than with monotherapy (18.8 vs. 12.6 months; HR = 0.739, 95% CI 0.544–1.003; log-rank P = 0.047), although the difference was of borderline statistical significance. Hematologic toxicities were more frequent with combination therapy but manageable.\n\nConclusions: In advanced EGFR-mutant NSCLC, baseline co-alteration patterns are associated with the magnitude of benefit from first-line combined chemotherapy. Patients with non-driver co-mutations may derive greater PFS and OS benefit from TKI plus chemotherapy, whereas those with EGFR mutation alone fare well with TKI monotherapy. Given the retrospective design, biological heterogeneity within subgroups, small driver-co-mutation sample size, and non-significant OS interaction, these findings are hypothesis-generating and require prospective validation before guiding individualized treatment decisions.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Western Pharmacy, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine-Hebei, Cangzhou, Hebei, China",
    "Department of Chemoradiotherapy and Hematology, Chengde Central Hospital, Chengde, Hebei, China",
    "Department of Hematological Oncology, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine-Hebei, Cangzhou, Hebei, China",
    "Department of Interventional and Breast Medical Oncology, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine-Hebei, Cangzhou, Hebei, China",
    "Department of Head, Neck and Thoracic Oncology, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine-Hebei, Cangzhou, Hebei, China",
    "National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Lili Bai"
    },
    {
      "affs": [
        1
      ],
      "name": "Huijie Wu"
    },
    {
      "affs": [
        2
      ],
      "name": "Yue Jiang"
    },
    {
      "affs": [
        3
      ],
      "name": "Dan Ran"
    },
    {
      "affs": [
        3
      ],
      "name": "Ying Li"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Jianxi Zhou"
    },
    {
      "affs": [
        3
      ],
      "name": "Teng Duan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6dcntjk3rfp96.bib",
  "cited_by": 0,
  "doi": "10.3389/fmed.2026.1969669",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731248/",
  "id": "6dcntjk3rfp96",
  "issns": [
    "2296-858X"
  ],
  "landing_url": "https://doi.org/10.3389/fmed.2026.1969669",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2740|Lung Cancer Treatments and Mutations"
    ]
  ],
  "openalex": "W7223089972",
  "pdf_url": "https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1969669/pdf",
  "pmcid": "PMC13731248",
  "pmid": "42984671",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/6dcntjk3rfp96.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:28Z",
      "native_id": "PMC13731248",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fmed.2026.1969669"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Lung Cancer Treatments and Mutations",
      "subfield": "general"
    }
  ],
  "title": "Genomic co-alteration patterns are associated with differential benefit from first-line third-generation EGFR-TKI plus chemotherapy versus TKI monotherapy in advanced EGFR-mutant NSCLC",
  "title_text": "Genomic co-alteration patterns are associated with differential benefit from first-line third-generation EGFR-TKI plus chemotherapy versus TKI monotherapy in advanced EGFR-mutant NSCLC",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:28Z",
  "url": "https://research.draconitic.com/paper/6dcntjk3rfp96",
  "venue": "Frontiers in Medicine",
  "versions": []
}