The association of azole antifungals with overall survival in patients with non-small cell lung cancer receiving immune checkpoint inhibitors.

IF 4.8 2区 医学 Q1 ONCOLOGY Oncologist Pub Date : 2025-02-06 DOI:10.1093/oncolo/oyae262
Nikhil T Sebastian, William A Stokes, Madhusmita Behera, Renjian Jiang, David A Gutman, Zhonglu Huang, Abigail Burns, Vidula Sukhatme, Michael C Lowe, Suresh S Ramalingam, Vikas P Sukhatme, Drew Moghanaki
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Abstract

Background: Preclinical data suggest antifungal azole derivatives have antitumor efficacy that may modulate response to immune checkpoint inhibitors (ICIs). We aimed to evaluate the association of azole drugs with overall survival (OS) in a population of patients with non-small cell lung cancer (NSCLC) treated with ICI within the Veterans Health Administration (VHA).

Methods: In this retrospective study, the VA Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant oral azole use was defined as dispensation by a VA pharmacy within 90 days of the first ICI infusion. Patients who received azole after 30 days were excluded from the analysis to mitigate immortal time bias. OS was measured from the start of ICI. Cox regression and propensity score matching were used to adjust for confounders.

Results: We identified 3413 patients with NSCLC receiving ICI; 324 (9.5%) were exposed to concomitant azoles. As a group, azole use was not associated with OS (hazard ratio [HR] = 0.96; 95% CI, 0.84-1.09; P = .51). After stratification by azole type, clotrimazole had an association with better OS on univariable (HR = 0.75; 95% CI, 0.59-0.96; P = .024) and multivariable analysis (HR = 0.71; 95% CI, 0.56-0.91; P = .007). Propensity score matching of patients who received clotrimazole vs no azole yielded 101 patients per matched cohort. Clotrimazole was associated with improved OS, although this did not meet the threshold for statistical significance (HR = 0.74; 0.54-1.01; P = .058).

Conclusion: This observational study demonstrated an association between clotrimazole and OS among patients with advanced NSCLC receiving ICI. These findings build upon preclinical evidence and support further investigation into the potential for clotrimazole as a repurposed FDA drug to improve cancer outcomes.

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唑类抗真菌药物与接受免疫检查点抑制剂治疗的非小细胞肺癌患者总生存期的关系。
背景:临床前数据表明,抗真菌唑衍生物具有抗肿瘤功效,可调节对免疫检查点抑制剂(ICIs)的反应。我们的目的是评估退伍军人健康管理局(VHA)中接受 ICI 治疗的非小细胞肺癌(NSCLC)患者中唑类药物与总生存期(OS)的关系:在这项回顾性研究中,我们在退伍军人健康管理局企业数据仓库中查询了2010年至2018年期间确诊为NSCLC并接受ICI治疗的患者。首次输注 ICI 后 90 天内由退伍军人事务部药房配药即为同时口服唑类药物。分析中排除了30天后接受阿唑治疗的患者,以减少不死时间偏倚。OS 从 ICI 输注开始计算。Cox回归和倾向评分匹配用于调整混杂因素:我们确定了3413名接受ICI治疗的NSCLC患者,其中324人(9.5%)同时使用了唑类药物。作为一个群体,使用唑类与OS无关(危险比[HR] = 0.96; 95% CI, 0.84-1.09; P = .51)。根据唑类进行分层后,克霉唑在单变量分析(HR = 0.75;95% CI,0.59-0.96;P = .024)和多变量分析(HR = 0.71;95% CI,0.56-0.91;P = .007)中与更好的OS相关。对接受克霉唑治疗与未接受唑类治疗的患者进行倾向评分匹配,每个匹配队列中有 101 名患者。克霉唑与OS的改善有关,但未达到统计学显著性阈值(HR = 0.74; 0.54-1.01; P = .058):这项观察性研究表明,在接受 ICI 治疗的晚期 NSCLC 患者中,克霉唑与 OS 之间存在关联。这些研究结果建立在临床前证据的基础上,支持进一步研究克霉唑作为 FDA 改用药物改善癌症预后的潜力。
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来源期刊
Oncologist
Oncologist 医学-肿瘤学
CiteScore
10.40
自引率
3.40%
发文量
309
审稿时长
3-8 weeks
期刊介绍: The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.
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