{
  "abstract": "Background\n\nBRAF V600E-mutant metastatic colorectal cancer (mCRC) represents an aggressive molecular subtype associated with poor prognosis and limited response to conventional chemotherapy. Although multiple targeted strategies, including anti-vascular endothelial growth factor (VEGF), anti-epidermal growth factor receptor (EGFR), and BRAF-directed therapies, are used in clinical practice, their comparative effectiveness remains uncertain. We performed a reconstructed individual patient-data (IPD) meta-analysis of randomized controlled trials (RCTs) to evaluate survival outcomes across targeted therapeutic classes in BRAF-mutant mCRC.Methods\n\nA systematic search of PubMed, Embase, Scopus, and Cochrane databases was conducted through July 2025 to identify RCTs reporting survival outcomes for BRAF-mutant mCRC. Kaplan-Meier curves were digitized and IPD reconstructed using established methods. A one-stage meta-analysis using Cox proportional hazards models was performed to estimate pooled overall survival (OS) and progression-free survival (PFS). Models were adjusted for study-level covariates and clustering, with Bonferroni correction applied for multiple comparisons.Results\n\nEighteen RCTs comprising 11,931 participants were included. Pooled median OS was 22.3 months for BRAF-directed regimens, 17.1 months for VEGF-targeted therapy, and 10.1 months for EGFR-directed therapy across studies evaluating first-line therapy. Across first-line studies, BRAF inhibitor directed regimen was associated with significantly improved OS compared with EGFR inhibition (HR 0.43, 95% CI 0.31-0.60; P < 0.001) and improved PFS (HR 0.47, 95% CI 0.42-0.53; P < 0.001). VEGF inhibition also demonstrated superior OS compared with EGFR inhibition (HR 0.56, 95% CI 0.38-0.81; p < 0.001). EGFR-directed regimen consistently demonstrated the poorest survival outcomes across analyses.Discussion\n\nIn this reconstructed IPD meta-analysis, BRAF-directed therapies were associated with the most favourable survival outcomes, whereas EGFR directed regimen demonstrated limited clinical benefit in BRAF-mutant mCRC. These results highlight the importance of biologically aligned pathway-targeted therapy and provide comparative evidence to inform treatment selection in this aggressive molecular subtype.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Internal Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, United States. skazmi1@pennstatehealth.psu.edu.",
    "Mayo Clinic School of Graduate Medical Education, Mayo Clinic, Rochester, MN, United States.",
    "Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, United States.",
    "Department of Internal Medicine, University of Central Florida, Tallahassee, FL, USA.",
    "Sindh Medical College, Jinnah Sindh Medical University, Karachi, Pakistan.",
    "Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan.",
    "Division of Hematology & Oncology, Department of Internal Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Syeda Kanza Kazmi",
      "orcid": "0000-0001-6386-6221"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Muhammad Abdul Rehman",
      "orcid": "0000-0003-3540-0998"
    },
    {
      "affs": [
        4
      ],
      "name": "Hanaa Tariq",
      "orcid": "0009-0004-8375-7304"
    },
    {
      "affs": [
        5
      ],
      "name": "Aqsa Kabir"
    },
    {
      "affs": [
        5
      ],
      "name": "Jalib Ahmed"
    },
    {
      "affs": [
        6
      ],
      "name": "Nelson Shu-Sang S Yee"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6ps52h1ndrnjb.bib",
  "cited_by": 0,
  "doi": "10.1007/s12029-026-01597-6",
  "fulltext_url": "https://europepmc.org/articles/PMC13719800",
  "id": "6ps52h1ndrnjb",
  "issns": [
    "1941-6628",
    "1941-6636"
  ],
  "landing_url": "https://europepmc.org/article/MED/42957919",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2730|Colorectal Cancer Treatments and Studies"
    ]
  ],
  "openalex": "W7224260601",
  "pdf_url": "https://europepmc.org/articles/PMC13719800?pdf=render",
  "pmcid": "PMC13719800",
  "pmid": "42957919",
  "published": "2026-10-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6ps52h1ndrnjb.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:36Z",
      "native_id": "MED:42957919",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42957919"
    },
    {
      "first_seen": "2026-11-02T12:23:42Z",
      "native_id": "PMC13719800",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s12029-026-01597-6"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Colorectal Cancer Treatments and Studies",
      "subfield": "oncology"
    }
  ],
  "title": "Survival Outcomes in Metastatic Colorectal Cancer Patients with BRAF Mutations Undergoing Targeted Chemotherapy: A Reconstructed Individual Patient Data Meta-Analysis of Randomized Controlled Trials.",
  "title_text": "Survival Outcomes in Metastatic Colorectal Cancer Patients with BRAF Mutations Undergoing Targeted Chemotherapy: A Reconstructed Individual Patient Data Meta-Analysis of Randomized Controlled Trials.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:20:48Z",
  "url": "https://research.draconitic.com/paper/6ps52h1ndrnjb",
  "venue": "Journal of gastrointestinal cancer",
  "versions": []
}