{
  "abstract": "Introduction: Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant lung cancer is associated with a poor prognosis, underscoring the need for effective pharmacological treatments. An exploratory subgroup analysis of IMpower150 suggested potential clinical benefit of the atezolizumab-containing regimen in KRAS-mutant non-squamous NSCLC, although prospective data remain limited. We prospectively evaluated its efficacy and safety and performed exploratory biomarker analyses.\n\nMethods: The study cohort comprised patients with advanced or recurrent KRAS-mutant non-squamous NSCLC scheduled to receive ICI plus bevacizumab-based chemotherapy at 10 Japanese institutions between January 2023 and December 2024. The primary endpoint was progression-free survival (PFS). Secondary endpoints included disease control rate (DCR), objective response rate (ORR), overall survival (OS), and safety. Associations between baseline serum levels of vascular endothelial growth factor (VEGF)-A and VEGF-D and treatment outcomes were explored in patients with available pretreatment samples.\n\nResults: Of 22 enrolled patients, 21 received treatment and were analyzed for efficacy and safety; 17 were analyzed for serum biomarkers. All patients received atezolizumab, bevacizumab, carboplatin, and paclitaxel. The median PFS and OS were 6.0 and 17.1 months, respectively. Among 19 patients with measurable disease, the ORR was 42.1%, and the DCR was 68.4%. Grade ≥3 hematologic and non-hematologic adverse events occurred in 33.3% and 47.6% of patients, respectively. Baseline serum VEGF-A and VEGF-D levels were not significantly associated with the treatment outcomes.\n\nConclusions: ICI plus bevacizumab-based chemotherapy showed an ORR of 42.1%, a median PFS of 6.0 months, and a median OS of 17.1 months in patients with KRAS-mutant non-squamous NSCLC. Given the small sample size and single-arm design, these findings should be considered descriptive and hypothesis-generating. Pretreatment serum VEGF-A and VEGF-D levels were not significantly associated with clinical outcomes, although limited statistical power precludes definitive conclusions. Larger comparative studies with comprehensive molecular profiling are warranted.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan",
    "Department of Respiratory Medicine, Shonan Fujisawa Tokushukai Hospital, Kanagawa, Fujisawa, Japan",
    "Department of Respiratory Medicine, Shonan Oiso Hospital, Kanagawa, Oiso, Japan",
    "Department of Respiratory Medicine, Fukuchiyama City Hospital, Kyoto, Japan",
    "Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan",
    "Department of Respiratory Medicine, Ichinomiya Nishi Hospital, Aichi, Ichinomiya, Japan",
    "Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Gunma, Japan",
    "Department of Respiratory Medicine, National Hospital Organization Omuta National Hospital, Omuta, Fukuoka, Japan",
    "Department of Breast Medical Oncology, Izumi City General Hospital, Izumi, Japan",
    "Department of Respiratory Medicine, Uji-Tokushukai Medical Center, Kyoto, Japan",
    "Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Masaki Ishida"
    },
    {
      "affs": [
        0
      ],
      "name": "Tadaaki Yamada"
    },
    {
      "affs": [
        1
      ],
      "name": "Riko Kamada"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Makoto Hibino"
    },
    {
      "affs": [
        3
      ],
      "name": "Masashi Egami"
    },
    {
      "affs": [
        3
      ],
      "name": "Takayuki Nakano"
    },
    {
      "affs": [
        4
      ],
      "name": "Tatsuya Imabayashi"
    },
    {
      "affs": [
        4
      ],
      "name": "Chieko Takumi"
    },
    {
      "affs": [
        5
      ],
      "name": "Koichi Ishida"
    },
    {
      "affs": [
        5
      ],
      "name": "Masafumi Takeshita"
    },
    {
      "affs": [
        6
      ],
      "name": "Ken Masubuchi"
    },
    {
      "affs": [
        7
      ],
      "name": "Miiru Izumi"
    },
    {
      "affs": [
        8
      ],
      "name": "Takayo Ota"
    },
    {
      "affs": [
        9
      ],
      "name": "Shoki Morito"
    },
    {
      "affs": [
        9
      ],
      "name": "Yusuke Chihara"
    },
    {
      "affs": [
        10
      ],
      "name": "Soichi Hirai"
    },
    {
      "affs": [
        10
      ],
      "name": "Shinsuke Shiotsu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ryo Sawada"
    },
    {
      "affs": [
        0
      ],
      "name": "Hayato Kawachi"
    },
    {
      "affs": [
        0
      ],
      "name": "Naoya Nishioka"
    },
    {
      "affs": [
        0
      ],
      "name": "Masahiro Iwasaku"
    },
    {
      "affs": [
        0
      ],
      "name": "Koichi Takayama"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1vybyfhsdxh90.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1875501",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696455/",
  "id": "1vybyfhsdxh90",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://doi.org/10.3389/fimmu.2026.1875501",
  "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": "W7221573040",
  "pdf_url": "https://europepmc.org/articles/PMC13696455?pdf=render",
  "pmcid": "PMC13696455",
  "pmid": "42935986",
  "published": "2026-10-12",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1vybyfhsdxh90.ris",
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  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Efficacy and safety of immune checkpoint inhibitor plus bevacizumab-based chemotherapy in advanced or recurrent KRAS-mutant non-squamous NSCLC: the SPIRAL-STONE study",
  "title_text": "Efficacy and safety of immune checkpoint inhibitor plus bevacizumab-based chemotherapy in advanced or recurrent KRAS-mutant non-squamous NSCLC: the SPIRAL-STONE study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:47Z",
  "url": "https://research.draconitic.com/paper/1vybyfhsdxh90",
  "venue": "Frontiers in Immunology",
  "versions": []
}