{
  "abstract": "Background\n\nBone metastases occur in approximately one-third of patients with metastatic clear-cell renal cell carcinoma (ccRCC) and are associated with poor prognosis. Although immune-oncology (IO)-based combinations are the standard first-line treatment, the relative efficacy of IO plus tyrosine kinase inhibitor (IO+TKI) versus dual immunotherapy (IO+IO) in this subgroup remains uncertain.Methods\n\nWe performed a systematic review and meta-analysis of phase III randomized trials comparing first-line IO-based combinations with sunitinib in treatment-naïve metastatic ccRCC. Eligible studies reported hazard ratios (HRs) for progression-free survival (PFS) and/or overall survival (OS) in patients with baseline bone metastases and had a median follow-up of at least 36 months. The primary analysis pooled IO+TKI trials, whereas the single eligible IO+IO study was analyzed separately. Fixed- and random-effects inverse-variance models were applied.Results\n\nThree phase III trials were included: CLEAR (lenvatinib plus pembrolizumab versus sunitinib), CheckMate 9ER (nivolumab plus cabozantinib versus sunitinib), and CheckMate 214 (nivolumab plus ipilimumab versus sunitinib). IO+TKI significantly improved PFS versus sunitinib (HR 0.46, 95% CI 0.35-0.61; p < 0.0001), with no heterogeneity (I² = 0%). In contrast, IO+IO showed no PFS benefit (HR 1.07, 95% CI 0.76-1.51). Pooling all trials introduced substantial heterogeneity (I² = 85.9%), and subgroup analysis confirmed a significant interaction between treatment class and PFS (p = 0.0002). IO+TKI also improved OS (HR 0.66, 95% CI 0.50-0.88; p = 0.0041), again without heterogeneity (I² = 0%). IO+IO showed a non-significant trend toward improved OS (HR 0.82, 95% CI 0.61-1.11), with no significant difference between treatment classes for OS (p = 0.314).Conclusions\n\nIn patients with metastatic ccRCC and bone metastases, IO+TKI combinations were associated with significant improvements in PFS and OS compared with sunitinib, whereas IO+IO did not improve PFS. These findings suggest that treatment strategy may influence outcomes in this high-risk subgroup.",
  "abstract_shown": true,
  "affiliations": [
    "Interdisciplinary Department of Medicine, University of Bari \"Aldo Moro\", Bari, Italy.",
    "Division of Medical Oncology, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Italy.",
    "University of São Paulo, São Paulo, Brazil.",
    "Unimed Sorocaba, Sorocaba, Brazil.",
    "Barretos Cancer Hospital (Hospital de Amor), Barretos, São Paulo, Brazil.",
    "Universidade Regional de Blumenau (FURB), Blumenau, Brazil."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Clara Fish Araujo de Albuquerque"
    },
    {
      "affs": [
        2
      ],
      "name": "Leila Caroline Souza Reis"
    },
    {
      "affs": [
        3
      ],
      "name": "Eliza Del Fiol Manna"
    },
    {
      "affs": [
        4
      ],
      "name": "Ana Elisa Saragossa Zafalon"
    },
    {
      "affs": [
        5
      ],
      "name": "Angela Theresa Zuffo Yabrude"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Camillo Porta"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/acmfz9eajb210.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jbo.2026.100806",
  "fulltext_url": "https://europepmc.org/articles/PMC13677974",
  "id": "acmfz9eajb210",
  "issns": [
    "2212-1366",
    "2212-1374"
  ],
  "landing_url": "https://europepmc.org/article/MED/42898627",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2740|Renal cell carcinoma treatment"
    ]
  ],
  "openalex": "W7220866852",
  "pdf_url": "https://europepmc.org/articles/PMC13677974?pdf=render",
  "pmcid": "PMC13677974",
  "pmid": "42898627",
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/acmfz9eajb210.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42898627",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42898627"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Renal cell carcinoma treatment",
      "subfield": "general"
    }
  ],
  "title": "Efficacy of immune-oncology combinations versus sunitinib in patients with bone metastases from renal cell carcinoma: A systematic review and meta-analysis of phase III trials with long-term follow-up.",
  "title_text": "Efficacy of immune-oncology combinations versus sunitinib in patients with bone metastases from renal cell carcinoma: A systematic review and meta-analysis of phase III trials with long-term follow-up.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/acmfz9eajb210",
  "venue": "Journal of bone oncology",
  "versions": []
}