Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Jikei University School of Medicine, Tokyo, Japan.
Clin Genitourin Cancer. 2024 Dec;22(6):102237. doi: 10.1016/j.clgc.2024.102237. Epub 2024 Oct 17.
Although immune checkpoint inhibitors (ICI) and/or tyrosine kinase inhibitors (TKI) are the standard treatment of advanced unresectable or metastatic renal cell carcinoma (RCC), the impact of concomitant medications remains unclear. We aimed to evaluate the impact of concomitant medications on survival outcomes in patients treated with systemic therapy for advanced unresectable or metastatic RCC. In August 2024, PubMed, Scopus, and Web of Science were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic RCC (PROSPERO: CRD42024573252). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis according to heterogeneity. We identified 22 eligible studies (5 prospective and 17 retrospective) comprising 16,072 patients. Concomitant medications included proton pump inhibitors (PPI) (n = 3959), antibiotics (n = 571), statins (n = 5466), renin-angiotensin system inhibitors (RASi) (n = 6615), and beta-blockers (n = 1964). Both concomitant PPI and antibiotics were significantly associated with worse OS in patients treated with ICI (PPI: HR: 1.22, P = .01, and antibiotics: HR: 2.09, P < .001). Concomitant statins, RASi, or beta-blocker were significantly associated with improved OS in patients treated with TKI (statins: HR: 0.81, P = .03, RASi: HR: 0.63, P < .001, beta-blocker: HR: 0.69, P < .001, respectively). In patients treated with ICI, RASi was significantly associated with improved OS (HR: 0.64, P = .02). Concomitant use of antibiotics or PPI with ICI can reduce its oncologic efficacy. Conversely, concomitant statins, RASi, or beta-blockers can enhance the oncologic efficacy of TKI. When initiating systemic therapy for metastatic RCC, it may be important for clinicians to assess baseline co-medications and recognize their possible positive or negative effects.
尽管免疫检查点抑制剂（ICI）和/或酪氨酸激酶抑制剂（TKI）是晚期不可切除或转移性肾细胞癌（RCC）的标准治疗方法，但伴随药物的影响仍不清楚。我们旨在评估伴随药物对接受晚期不可切除或转移性 RCC 系统治疗的患者生存结局的影响。2024 年 8 月，检索了评估晚期不可切除或转移性 RCC 患者伴随药物的研究（PROSPERO：CRD42024573252），包括 PubMed、Scopus 和 Web of Science。主要结局是总生存（OS）。根据异质性，采用固定或随机效应模型进行荟萃分析。我们确定了 22 项符合条件的研究（5 项前瞻性和 17 项回顾性），包括 16072 名患者。伴随药物包括质子泵抑制剂（PPI）（n = 3959）、抗生素（n = 571）、他汀类药物（n = 5466）、肾素-血管紧张素系统抑制剂（RASi）（n = 6615）和β受体阻滞剂（n = 1964）。ICI 治疗患者中，伴随 PPI 和抗生素均与 OS 较差显著相关（PPI：HR：1.22，P =.01；抗生素：HR：2.09，P <.001）。TKI 治疗患者中，伴随他汀类药物、RASi 或β受体阻滞剂与 OS 改善显著相关（他汀类药物：HR：0.81，P =.03；RASi：HR：0.63，P <.001；β受体阻滞剂：HR：0.69，P <.001）。ICI 治疗患者中，RASi 与 OS 改善显著相关（HR：0.64，P =.02）。ICI 伴随使用抗生素或 PPI 可能降低其肿瘤疗效。相反，伴随使用他汀类药物、RASi 或β受体阻滞剂可能增强 TKI 的肿瘤疗效。当开始转移性 RCC 的系统治疗时，临床医生评估基线伴随药物并认识到它们可能的积极或消极影响可能很重要。
