期刊
EUROPEAN JOURNAL OF CANCER
卷 142, 期 -, 页码 18-28出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2020.09.033
关键词
Concomitant medications; Drugs; Immunotherapy; Corticosteroids; Proton-pump inhibitors; Antibiotics; Immune checkpoint inhibitors; Cancer patients; Score; Index; Prognostic
类别
资金
- Welcome Trust Strategic Fund [PS3416]
- NIHR Imperial Biomedical Research Centre (BRC) ITMAT Push for Impact Scheme 2019
- Consorzio Interuniversitario Nazionale per la Bio-Oncologia
Corticosteroids, antibiotics, and proton-pump inhibitors were found to have a significant impact on the outcomes of patients treated with ICIs. A drug-based prognostic score was proposed based on these medications, which proved to be valuable in stratifying patients and could be useful in routine practice and clinical trials involving ICIs.
Background: Concomitant medications are known to impact on clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs). We aimed weighing the role of different concomitant baseline medications to create a drug-based prognostic score. Methods: We evaluated concomitant baseline medications at immunotherapy initiation for their impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in a single-institution cohort of patients with advanced cancer treated with ICIs (training cohort, N = 217), and a drug-based prognostic score with the drugs resulting significantly impacting the OS was computed. Secondly, we externally validated the score in a large multicenter external cohort (n = 1012). Results: In the training cohort (n=217), the median age was 69 years (range: 32-89), and the primary tumours were nonesmall-cell lung cancer (70%), melanoma (14.7%), renal cell carcinoma (9.2%) and others (6%). Among baseline medications, corticosteroids (hazard ratio [HR] = 2.3; 95% confidence interval [ CI]: 1.60-3.30), systemic antibiotics (HR = 2.07; 95% CI: 1.31-3.25) and proton-pump inhibitors (PPIs) (HR = 1.57; 95% CI: 1.13-2.18) were significantly associated with OS. The prognostic score was calculated using these three drug classes, defining good, intermediate and poor prognosis patients. Within the training cohort, OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0297) were significantly distinguished by the score stratification. The prognostic value of the score was also demonstrated in terms of OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0006) within the external cohort. Conclusion: Cumulative exposure to corticosteroids, antibiotics and PPIs (three likely microbiota-modulating drugs) leads to progressively worse outcomes after ICI therapy. We propose a simple score that can help stratifying patients in routine practice and clinical trials of ICIs. (C) 2020 Elsevier Ltd. All rights reserved.
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