E Pérez-Ruiz1, J Jiménez-Castro2, M-A Berciano-Guerrero3, J Valdivia4, S Estalella-Mendoza5, F Toscano6, M Rodriguez de la Borbolla Artacho7, M Garrido-Siles8, M J Martínez-Bautista9, R Villatoro Roldan10, F Rivas-Ruiz11, E Nogales-Fernández12, C Morales13, B Pérez-Valderrama2, L De la Cruz-Merino12, A Rueda3. 1. Oncology Department, Hospital Costa del Sol, Autovía A-7, Km 187, C.P. 29603, Marbella, Málaga, Spain. eliperu@gmail.com. 2. Oncology Department, Hospital Virgen del Rocío, Seville, Spain. 3. Interinstitutional Oncology Unit, Institute of Biomedical Research in Málaga (IBIMA), Hospitales Universitarios Regional y Virgen de la Victoria (HURyVV), Malaga, Spain. 4. Oncology Department, Hospital Virgen de las Nieves, Granada, Spain. 5. Oncology Department, Hospital Puerta del Mar, Cádiz, Spain. 6. Oncology Department, Hospital Juan Ramón Jiménez, Huelva, Spain. 7. Oncology Department, Hospital de Valme, Seville, Spain. 8. Pharmacy Department, Hospital Costa del Sol, Marbella, Spain. 9. Pharmacy Department, Hospital Puerta del Mar, Cádiz, Spain. 10. Oncology Department, Hospital Costa del Sol, Autovía A-7, Km 187, C.P. 29603, Marbella, Málaga, Spain. 11. Research Support Unit, Hospital Costa del Sol, Marbella, Spain. 12. Oncology Department, Hospital Virgen Macarena, Seville, Spain. 13. Oncology Department, Hospital Reina Sofía, Córdoba, Spain.
Abstract
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.
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.
Authors: Mora Guardamagna; Miguel-Angel Berciano-Guerrero; Beatriz Villaescusa-González; Elisabeth Perez-Ruiz; Javier Oliver; Rocío Lavado-Valenzuela; Antonio Rueda-Dominguez; Isabel Barragán; María Isabel Queipo-Ortuño Journal: Int J Mol Sci Date: 2022-10-09 Impact factor: 6.208