{
  "abstract": "Background: Lenvatinib plus pembrolizumab is an established treatment for patients with previously treated advanced or recurrent endometrial cancer. In routine practice, clinicians may select a lenvatinib starting dose below 20 mg for patients expected to have limited tolerance, but the comparative effectiveness and tolerability of that strategy remain uncertain.\n\nMethods: We searched PubMed/MEDLINE, Web of Science Core Collection, and Cochrane CENTRAL from inception to 11 July 2026, with source-specific updates completed on 13–14 July 2026. Comparative observational studies of adults receiving lenvatinib plus pembrolizumab were eligible. The primary estimand compared starting doses below 20 mg with 20 mg; a 10-mg threshold contrast and first-8-week relative dose intensity were kept separate. Binary outcomes were summarized as risk ratios (RRs) and time-to-event outcomes as hazard ratios (HRs). Risk of bias was assessed with ROBINS-I, missing-evidence bias with ROB-ME, and certainty with GRADE.\n\nResults: Ten studies representing 10 independent cohorts and 1,000 patients were included. Five cohorts (703 patients in total) informed the primary starting-dose comparison, with outcome-specific analysis denominators. For starting doses below 20 mg versus 20 mg, the pooled RR was 0.97 for objective response (95% confidence interval [CI], 0.70–1.34; I²=11.9%) and 0.96 for disease control (95% CI, 0.83–1.11; I²=0%). The RR for subsequent lenvatinib dose reduction was 0.66 (95% CI, 0.34–1.27; I²=27.4%). Estimates for interruption, permanent discontinuation, grade 3 or higher adverse events, and progression-free survival were imprecise; hospitalization and treatment persistence were not poolable. Every evaluated result had serious overall risk of bias, and certainty was very low for all pooled comparisons.\n\nConclusion: Comparative observational evidence does not establish that starting lenvatinib below 20 mg preserves antitumor effectiveness or improves tolerability relative to a 20 mg starting dose. Prospective, confounder-aware comparative studies are needed before a reduced starting-dose strategy can be recommended broadly.\n\nSystematic review registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261458417.",
  "abstract_shown": true,
  "affiliations": [
    "Dongzhimen Hospital, Beijing University of Chinese Medicine",
    "School of Life Science, Beijing University of Chinese Medicine"
  ],
  "article_type": "systematic review",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yu Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Juncheng Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Chuyue Chang"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengfei Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Runbing Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shi Dong"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Miao Jiang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3wgejn90sg3mn.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1965694",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719303/?tool=EBI",
  "id": "3wgejn90sg3mn",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1965694/full",
  "language": "eng",
  "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",
      "Systematic Review"
    ],
    [
      "openalex",
      "2729|Endometrial and Cervical Cancer Treatments"
    ]
  ],
  "openalex": "W7222528188",
  "pdf_url": "https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1965694/pdf",
  "pmcid": "PMC13719303",
  "pmid": "42964024",
  "published": "2026-10-16",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/3wgejn90sg3mn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1965694",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1965694/full"
    },
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC:PMC13719303",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13719303"
    },
    {
      "first_seen": "2026-11-02T12:23:17Z",
      "native_id": "PMC13719303",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fonc.2026.1965694"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2729|Endometrial and Cervical Cancer Treatments",
      "subfield": "reproductive-child"
    }
  ],
  "title": "Lenvatinib starting doses below 20 mg versus 20 mg with pembrolizumab in advanced or recurrent endometrial cancer: a systematic review and meta-analysis of comparative observational evidence",
  "title_text": "Lenvatinib starting doses below 20 mg versus 20 mg with pembrolizumab in advanced or recurrent endometrial cancer: a systematic review and meta-analysis of comparative observational evidence",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:20:23Z",
  "url": "https://research.draconitic.com/paper/3wgejn90sg3mn",
  "venue": "Frontiers in Oncology",
  "versions": []
}