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Impact of concomitant fibrates on immunotherapy outcomes for advanced non-small cell lung cancer.
Stokes, William A; Behera, Madhusmita; Jiang, Renjian; Gutman, David A; Huang, Zhonglu; Burns, Abigail; Sebastian, Nikhil T; Sukhatme, Vidula; Lowe, Michael C; Ramalingam, Suresh S; Sukhatme, Vikas P; Moghanaki, Drew.
Afiliação
  • Stokes WA; Department of Radiation Oncology, Emory University, Atlanta, Georgia, USA.
  • Behera M; Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
  • Jiang R; Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
  • Gutman DA; Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
  • Huang Z; Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
  • Burns A; Atlanta Veterans Affairs Health Care System, Decatur, Georgia, USA.
  • Sebastian NT; Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
  • Sukhatme V; Atlanta Veterans Affairs Health Care System, Decatur, Georgia, USA.
  • Lowe MC; Department of Radiation Oncology, Emory University, Atlanta, Georgia, USA.
  • Ramalingam SS; Winship Cancer Institute, Emory University, Atlanta, Georgia, USA.
  • Sukhatme VP; Morningside Center for Innovative and Affordable Medicine, Emory University, Atlanta, Georgia, USA.
  • Moghanaki D; GlobalCures, Inc, Newton, Massachusetts, USA.
Cancer Med ; 12(1): 358-367, 2023 01.
Article em En | MEDLINE | ID: mdl-35607930
BACKGROUND: Peroxisome proliferator-activated receptor agonists such as fibrates restore oxidative metabolism in cytotoxic T-lymphocytes, thereby enhancing response to immune checkpoint inhibitors (ICI) in preclinical models. However, there is no evidence in humans on the clinical impact of fibrates as an adjunct to ICI. METHODS: In this cohort study of Veterans with non-small cell lung cancer (NSCLC) receiving ICI, fibrate exposure was defined as a prescription filled within 90 days of an ICI infusion. Overall survival (OS), measured from the start of ICI, was compared between exposed and unexposed Veterans. Cox multivariable analysis (MVA) was used to identify factors associated with OS. A sensitivity analysis of Veterans with stage IV NSCLC who received docetaxel without ICI was similarly performed. RESULTS: The ICI cohort included 3593 Veterans, of whom 301 (8.5%) coincidentally received a fibrate. Veterans receiving fibrates were more likely to be older, white, male, and married, and to have greater comorbidity burden, but less likely to receive chemotherapy. Coincidental fibrates were associated with improved OS both on MVA (HR 0.86, 95%CI 0.75-0.99) and in a matched subset (HR 0.75, 95%CI 0.63-0.90). In contrast, among the cohort of 968 Veterans treated with chemotherapy, fibrates did not have a significant impact on OS by MVA (HR 0.99, 95%CI 0.79-1.25) or in a matched subset (HR 1.02, 95%CI CI 0.75-1.39). CONCLUSIONS: Concomitant fibrates are associated with improved OS among NSCLC patients receiving ICI but not among those receiving chemotherapy. This hypothesis-generating observation supports a potential role for fibrates as an adjunct to immunotherapy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Cancer Med Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma Pulmonar de Células não Pequenas / Neoplasias Pulmonares Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans / Male Idioma: En Revista: Cancer Med Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos