Impact of Renin-Angiotensin System Inhibitors on Response to PD1/L1 Inhibitors in Patients With Metastatic Renal Cell Carcinoma

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer Pub Date : 2024-11-01 DOI:10.1016/j.clgc.2024.102256

Kathryn Fortune , Soham Ali , Jack Masur , Paul Viscuse , Michael Devitt , Robert Dreicer , William Paul Skelton IV

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引用次数: 0

Abstract

Background

The renin-angiotensin-aldosterone system (RAAS), traditionally associated with blood pressure and fluid regulation, also plays a role in tumorigenesis. Renin-angiotensin-aldosterone system inhibitors (RAASI), including angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs), have been shown to improve outcomes in various malignant neoplasms. In metastatic urothelial cancer, the use of RAASI have been associated with higher rates of tumor regression in patients receiving immunotherapy (IO) with PD1/L1 inhibitors. This is thought to be due to RAASI-induced downregulation of TGF-beta, for which increased expression is a known mechanism of PD1/L1 inhibitor resistance. We hypothesized that concurrent RAASI in patients with mRCC receiving IO is associated with increased tumor regression.

Methods

We conducted a retrospective analysis of patients with mRCC receiving IO as a first- or second-line therapy from 2016-2023 at the University of Virginia. A logistic regression model was used to evaluate the impact of concurrent RAASI on tumor regression. The primary endpoint was any regression of tumor on imaging.

Results

Data were available for 128 patients with mRCC who received IO as a first- (n = 91, 71.0%) or second- (n = 37, 28.9%) line treatment. Patients who received RAASI during IO were more likely to have tumor regression compared to patients who were not on concurrent RAASI (OR 3.84 [95% CI 1.81-8.47, P =< .001). This held true regardless if patients received IO as a first-line (OR 2.83 [95% CI 1.2-6.94], P = .0173) or second-line (OR 9.5 [95% CI 1.89-73.1], P = .005) treatment.

Conclusions

Our hypothesis generating study suggests that in our mRCC population, concurrent use of RAASI in patients receiving IO was associated with a significantly increased likelihood of tumor regression. These findings highlight the potential therapeutic advantage of RAASI in combination with IO for mRCC patients. Further exploration of this association is warranted in prospective studies to improve treatment outcomes for this patient population.

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肾素-血管紧张素系统抑制剂对转移性肾细胞癌患者对 PD1/L1 抑制剂反应的影响

背景肾素-血管紧张素-醛固酮系统（RAAS）传统上与血压和体液调节有关，但也在肿瘤发生中发挥作用。肾素-血管紧张素-醛固酮系统抑制剂（RAASI），包括血管紧张素转换酶抑制剂（ACEI）和血管紧张素受体阻滞剂（ARB），已被证明可改善各种恶性肿瘤的预后。在转移性尿路上皮癌中，使用 RAASI 与接受 PD1/L1 抑制剂免疫疗法（IO）的患者肿瘤消退率较高有关。这被认为是由于 RAASI 诱导了 TGF-beta 的下调，而 TGF-beta 的表达增加是 PD1/L1 抑制剂耐药的已知机制。我们假设，接受 IO 的 mRCC 患者同时接受 RAASI 与肿瘤消退增加有关。方法我们对弗吉尼亚大学 2016-2023 年期间接受 IO 作为一线或二线疗法的 mRCC 患者进行了回顾性分析。我们使用逻辑回归模型评估了同时使用 RAASI 对肿瘤消退的影响。结果 128 名接受 IO 作为一线（n = 91，71.0%）或二线（n = 37，28.9%）治疗的 mRCC 患者的数据可用。与未同时接受 RAASI 治疗的患者相比，在 IO 期间接受 RAASI 治疗的患者更有可能出现肿瘤消退（OR 3.84 [95% CI 1.81-8.47，P =< .001）。无论患者是将 IO 作为一线治疗（OR 2.83 [95% CI 1.2-6.94]，P = .0173）还是二线治疗（OR 9.5 [95% CI 1.89-73.1]，P = .005），情况都是如此。这些发现凸显了 RAASI 联合 IO 对 mRCC 患者的潜在治疗优势。有必要在前瞻性研究中进一步探讨这种关联，以改善这类患者的治疗效果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical genitourinary cancer 医学-泌尿学与肾脏学

CiteScore

5.20

自引率

6.20%

发文量

201

审稿时长

54 days

期刊介绍： Clinical Genitourinary Cancer is a peer-reviewed journal that publishes original articles describing various aspects of clinical and translational research in genitourinary cancers. Clinical Genitourinary Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of genitourinary cancers. The main emphasis is on recent scientific developments in all areas related to genitourinary malignancies. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.