Concomitant exposure to benzodiazepines during pembrolizumab-based therapy for advanced non-small-cell lung cancer: a propensity-score matched analysis of monitoring agency data
Aim: The interaction of concomitant benzodiazepine (BZD) exposure during immune checkpoint blockade has not been comprehensively investigated to date. This research aimed to determine the influence of BZD intake on the survival outcomes of patients with metastatic non-small-cell lung cancer (NSCLC)...
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Open Exploration Publishing Inc.
2025-01-01
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| Series: | Exploration of Targeted Anti-tumor Therapy |
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| Online Access: | https://www.explorationpub.com/uploads/Article/A1002287/1002287.pdf |
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| author | Fabrizio Nelli Enzo Maria Ruggeri Antonella Virtuoso Diana Giannarelli Armando Raso Federica Natoni Gloria Pessina Daniele Remotti Mario Giovanni Chilelli Carlo Signorelli Agnese Fabbri |
| author_facet | Fabrizio Nelli Enzo Maria Ruggeri Antonella Virtuoso Diana Giannarelli Armando Raso Federica Natoni Gloria Pessina Daniele Remotti Mario Giovanni Chilelli Carlo Signorelli Agnese Fabbri |
| author_sort | Fabrizio Nelli |
| collection | DOAJ |
| description | Aim: The interaction of concomitant benzodiazepine (BZD) exposure during immune checkpoint blockade has not been comprehensively investigated to date. This research aimed to determine the influence of BZD intake on the survival outcomes of patients with metastatic non-small-cell lung cancer (NSCLC) receiving pembrolizumab-based therapies. Methods: We included consecutive patients with advanced NSCLC who were given frontline pembrolizumab, whether as exclusive therapy or combined with platinum-based chemotherapy. The classification of BZD relied on the molecular composition, distinguishing between N-substituted and N-unsubstituted compounds. Results: During the time frame from April 2018 to May 2023, we enrolled 258 patients, 156 (60.5%) and 102 (39.5%) of whom received pembrolizumab alone or the combination regimen, respectively. We identified 108 (41.8%) exposed patients (BZD cohort) in comparison to all others (no-BZD cohort). After applying propensity-score matching, 108 cases were relevant for each cohort. After a median follow-up of 16.3 [95% confidence interval (CI) 13.1–19.7] months, univariate analysis revealed no significant differences in terms of progression-free survival (PFS) or overall survival (OS) between BZD cohorts. However, patients exposed to N-substituted compounds had significantly longer PFS and OS than those who did not take BZD. Conversely, patients exposed to N-unsubstituted compounds experienced significantly shortened OS. Multivariate testing showed that taking unspecified BZD had no impact on PFS or OS, while N-substituted BZD exposure correlated independently with longer PFS [hazard ratio (HR) 0.52 (95% CI 0.34–0.79); P = 0.002] and OS [HR 0.58 (95% CI 0.38–0.88); P < 0.001]. In contrast, N-unsubstituted BZD intake had worsening effects on OS [HR 1.92 (95% CI 1.20–3.06); P = 0.006]. Conclusions: BZD exposure may impact the efficacy of immune checkpoint inhibitors in patients with advanced NSCLC. The specific composition may influence the choice among different compounds. |
| format | Article |
| id | doaj-art-9c454423381149dfa703eaa610f655b1 |
| institution | Kabale University |
| issn | 2692-3114 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Targeted Anti-tumor Therapy |
| spelling | doaj-art-9c454423381149dfa703eaa610f655b12025-01-26T08:32:27ZengOpen Exploration Publishing Inc.Exploration of Targeted Anti-tumor Therapy2692-31142025-01-016100228710.37349/etat.2025.1002287Concomitant exposure to benzodiazepines during pembrolizumab-based therapy for advanced non-small-cell lung cancer: a propensity-score matched analysis of monitoring agency dataFabrizio Nelli0Enzo Maria Ruggeri1https://orcid.org/0000-0001-7790-0056Antonella Virtuoso2https://orcid.org/0000-0001-8888-9657Diana Giannarelli3https://orcid.org/0000-0002-6085-1195Armando Raso4https://orcid.org/0000-0003-1273-9905Federica Natoni5https://orcid.org/0000-0002-8320-584XGloria Pessina6https://orcid.org/0000-0003-3315-4762Daniele Remotti7https://orcid.org/0009-0009-9428-9207Mario Giovanni Chilelli8Carlo Signorelli9https://orcid.org/0000-0001-9710-4962Agnese Fabbri10https://orcid.org/0000-0002-3357-6343Department of Oncology and Hematology, Thoracic Oncology Unit, Central Hospital of Belcolle, 01100 Viterbo, ItalyDepartment of Oncology and Hematology, Medical Oncology Unit, Central Hospital of Belcolle, 01100 Viterbo, ItalyDepartment of Oncology and Hematology, Thoracic Oncology Unit, Central Hospital of Belcolle, 01100 Viterbo, ItalyBiostatistics Unit, Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00136 Rome, ItalyDepartment of Oncology and Hematology, Thoracic and Interventional Radiology, Central Hospital of Belcolle, 01100 Viterbo, ItalyDepartment of Oncology and Hematology, Molecular Biology and Genetics, Central Hospital of Belcolle, 0100 Viterbo, ItalyDepartment of Oncology and Hematology, Molecular Biology and Genetics, Central Hospital of Belcolle, 0100 Viterbo, ItalyDepartment of Oncology and Hematology, Pathology Unit, Central Hospital of Belcolle, 01100 Viterbo, ItalyDepartment of Oncology and Hematology, Medical Oncology Unit, Central Hospital of Belcolle, 01100 Viterbo, ItalyDepartment of Oncology and Hematology, Medical Oncology Unit, Central Hospital of Belcolle, 01100 Viterbo, ItalyDepartment of Oncology and Hematology, Medical Oncology Unit, Central Hospital of Belcolle, 01100 Viterbo, ItalyAim: The interaction of concomitant benzodiazepine (BZD) exposure during immune checkpoint blockade has not been comprehensively investigated to date. This research aimed to determine the influence of BZD intake on the survival outcomes of patients with metastatic non-small-cell lung cancer (NSCLC) receiving pembrolizumab-based therapies. Methods: We included consecutive patients with advanced NSCLC who were given frontline pembrolizumab, whether as exclusive therapy or combined with platinum-based chemotherapy. The classification of BZD relied on the molecular composition, distinguishing between N-substituted and N-unsubstituted compounds. Results: During the time frame from April 2018 to May 2023, we enrolled 258 patients, 156 (60.5%) and 102 (39.5%) of whom received pembrolizumab alone or the combination regimen, respectively. We identified 108 (41.8%) exposed patients (BZD cohort) in comparison to all others (no-BZD cohort). After applying propensity-score matching, 108 cases were relevant for each cohort. After a median follow-up of 16.3 [95% confidence interval (CI) 13.1–19.7] months, univariate analysis revealed no significant differences in terms of progression-free survival (PFS) or overall survival (OS) between BZD cohorts. However, patients exposed to N-substituted compounds had significantly longer PFS and OS than those who did not take BZD. Conversely, patients exposed to N-unsubstituted compounds experienced significantly shortened OS. Multivariate testing showed that taking unspecified BZD had no impact on PFS or OS, while N-substituted BZD exposure correlated independently with longer PFS [hazard ratio (HR) 0.52 (95% CI 0.34–0.79); P = 0.002] and OS [HR 0.58 (95% CI 0.38–0.88); P < 0.001]. In contrast, N-unsubstituted BZD intake had worsening effects on OS [HR 1.92 (95% CI 1.20–3.06); P = 0.006]. Conclusions: BZD exposure may impact the efficacy of immune checkpoint inhibitors in patients with advanced NSCLC. The specific composition may influence the choice among different compounds.https://www.explorationpub.com/uploads/Article/A1002287/1002287.pdfconcomitant medicationsnon-small-cell lung cancerimmune checkpoint blockadepembrolizumabchemotherapyfirst-line therapybenzodiazepinesefficacy |
| spellingShingle | Fabrizio Nelli Enzo Maria Ruggeri Antonella Virtuoso Diana Giannarelli Armando Raso Federica Natoni Gloria Pessina Daniele Remotti Mario Giovanni Chilelli Carlo Signorelli Agnese Fabbri Concomitant exposure to benzodiazepines during pembrolizumab-based therapy for advanced non-small-cell lung cancer: a propensity-score matched analysis of monitoring agency data Exploration of Targeted Anti-tumor Therapy concomitant medications non-small-cell lung cancer immune checkpoint blockade pembrolizumab chemotherapy first-line therapy benzodiazepines efficacy |
| title | Concomitant exposure to benzodiazepines during pembrolizumab-based therapy for advanced non-small-cell lung cancer: a propensity-score matched analysis of monitoring agency data |
| title_full | Concomitant exposure to benzodiazepines during pembrolizumab-based therapy for advanced non-small-cell lung cancer: a propensity-score matched analysis of monitoring agency data |
| title_fullStr | Concomitant exposure to benzodiazepines during pembrolizumab-based therapy for advanced non-small-cell lung cancer: a propensity-score matched analysis of monitoring agency data |
| title_full_unstemmed | Concomitant exposure to benzodiazepines during pembrolizumab-based therapy for advanced non-small-cell lung cancer: a propensity-score matched analysis of monitoring agency data |
| title_short | Concomitant exposure to benzodiazepines during pembrolizumab-based therapy for advanced non-small-cell lung cancer: a propensity-score matched analysis of monitoring agency data |
| title_sort | concomitant exposure to benzodiazepines during pembrolizumab based therapy for advanced non small cell lung cancer a propensity score matched analysis of monitoring agency data |
| topic | concomitant medications non-small-cell lung cancer immune checkpoint blockade pembrolizumab chemotherapy first-line therapy benzodiazepines efficacy |
| url | https://www.explorationpub.com/uploads/Article/A1002287/1002287.pdf |
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