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Combination therapy with immune checkpoint inhibitors and denosumab improves clinical outcomes in non-small cell lung cancer with bone metastases.
Asano, Yohei; Yamamoto, Norio; Demura, Satoru; Hayashi, Katsuhiro; Takeuchi, Akihiko; Kato, Satoshi; Miwa, Shinji; Igarashi, Kentaro; Higuchi, Takashi; Taniguchi, Yuta; Okuda, Miho; Matsumoto, Isao; Yano, Seiji; Tsuchiya, Hiroyuki.
Afiliación
  • Asano Y; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
  • Yamamoto N; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan. Electronic address: norinori@med.kanazawa-u.ac.jp.
  • Demura S; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
  • Hayashi K; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
  • Takeuchi A; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
  • Kato S; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
  • Miwa S; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
  • Igarashi K; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
  • Higuchi T; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
  • Taniguchi Y; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
  • Okuda M; Department of Radiology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8640, Japan.
  • Matsumoto I; Department of Thoracic Surgery, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa 920-8640, Japan.
  • Yano S; Department of Respiratory Medicine, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
  • Tsuchiya H; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Lung Cancer ; 193: 107858, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38901176
ABSTRACT

BACKGROUND:

The concomitant use of denosumab and immune checkpoint inhibitor (ICI) treatment may have synergistic effects and enhance antitumor activity; however, this has not been fully evaluated. This study aimed to evaluate the clinical outcomes of non-small cell lung cancer (NSCLC) patients with bone metastases receiving combination therapy and to identify the best combination regimen.

METHODS:

Eighty-six NSCLC patients with bone metastases who received ICI treatment were enrolled in this study. The patients were divided into two groups; a denosumab combination group (D + ICI group; n = 47) and a non-combination group (non-D + ICI group; n = 39). The response rate (RR) for bone metastases, disease control rate (DCR), overall survival (OS), real world progression-free survival (rwPFS), and the incidence of immune-related adverse events (irAEs) were evaluated. Additionally, the time when denosumab treatment should commence and concomitant treatment duration were evaluated.

RESULTS:

The D + ICI group showed significantly better RR (40.4 % vs. 20.5 %, p = 0.01), DCR (67.3 % vs. 38.7 %, p = 0.02), OS (14.2 vs. 8.6 months, p = 0.02), and rwPFS (7.4 vs. 3.6 months, p < 0.01) than the non-D + ICI group; however, incidence of irAEs showed no difference (29.7 % vs. 12.8 %, p = 0.07). Although clinical outcomes did not differ regardless of whether denosumab was initiated before or after ICI treatment, the group that received concomitant denosumab for more than four months had significantly better RR (46.2 % vs. 17.4 %, p = 0.03), OS (20.3 vs. 3.8 months, p < 0.01), and rwPFS (10.9 vs. 2.8 months, p < 0.01) than the group that received concomitant denosumab for less than four months. However, the landmark analysis showed no significant differences in OS (20.4 vs. 12.7 months, p = 0.11) and rwPFS (22.8 vs. 11.2 months, p = 0.21), and the results of denosumab duration were influenced by long-term survivors.

CONCLUSION:

Denosumab showed favorable synergistic effects with ICI treatment and may significantly improve the response to bone metastasis and prognosis without increasing the incidence of irAEs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Óseas / Protocolos de Quimioterapia Combinada Antineoplásica / Carcinoma de Pulmón de Células no Pequeñas / Denosumab / Inhibidores de Puntos de Control Inmunológico / Neoplasias Pulmonares Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Lung Cancer Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Óseas / Protocolos de Quimioterapia Combinada Antineoplásica / Carcinoma de Pulmón de Células no Pequeñas / Denosumab / Inhibidores de Puntos de Control Inmunológico / Neoplasias Pulmonares Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Lung Cancer Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Irlanda