Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice

• J. Jiménez-Castro ^[6] ; E. Pérez-Ruiz ^[1] ; M.-A. Berciano-Guerrero ^[7] ; J. Valdivia ^[8] ; S. Estalella-Mendoza ^[9] ; F. Toscano ^[2] ; M. Rodriguez de la Borbolla Artacho ^[3] ; M. Garrido-Siles ^[1] ; M. J. Martínez-Bautista ^[10] ; R. Villatoro Roldan ^[1] ; F. Rivas-Ruiz ^[11] ; E. Nogales-Fernández ^[4] ; C. Morales ^[5] ; B. Pérez-Valderrama ^[6] ; L. De la Cruz-Merino ^[4] ; A. Rueda ^[7]
  1. [1] Hospital Costa Del Sol

     Hospital Costa Del Sol

     Marbella, España

     
  2. [2] Hospital Juan Ramón Jiménez

     Hospital Juan Ramón Jiménez

     Huelva, España

     
  3. [3] Hospital Universitario de Valme

     Hospital Universitario de Valme

     Sevilla, España

     
  4. [4] Hospital Universitario Virgen Macarena

     Hospital Universitario Virgen Macarena

     Sevilla, España

     
  5. [5] Hospital Reina Sofía

     Hospital Reina Sofía

     Tudela, España

     
  6. [6] Oncology Department, Hospital Virgen del Rocío, Seville, Spain
  7. [7] Interinstitutional Oncology Unit, Institute of Biomedical Research in Málaga (IBIMA), Hospitales Universitarios Regional y Virgen de la Victoria (HURyVV), Malaga, Spain
  8. [8] Oncology Department, Hospital Virgen de las Nieves, Granada, Spain
  9. [9] Oncology Department, Hospital Puerta del Mar, Cádiz, Spain
  10. [10] Pharmacy Department, Hospital Puerta del Mar, Cádiz, Spain
  11. [11] Research Support Unit, Hospital Costa del Sol, Marbella, Spain

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 22, Nº. 10, 2020, págs. 1778-1785
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Purpose Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice.

    Materials and methods A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan–Meier method, was performed, and association with various independent variables was assessed using Cox regression.

    Results We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07–3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77–9.92; P < .001).

    Conclusion Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.