Immune-Related Adverse Events Can Predict Progression-Free and Overall Survival In Patients With Metastatic Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors

IF 2.3 3区医学 Q3 ONCOLOGY Clinical genitourinary cancer Pub Date : 2024-07-17 DOI:10.1016/j.clgc.2024.102164

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Abstract

Background

Different combination therapies using anti - PD-1 / PD-L1 or CTLA-4 immune checkpoint inhibition (ICI) are widely used in patients with metastatic renal cell carcinoma (mRCC). In the absents of established biomarkers, immune-related adverse events (irAEs) have been discussed as potential predictors of response.

Methods

In this retrospective cohort study, data of 134 patients with mRCC undergoing ICI treatment (Nivolumab, Ipilimumab and Nivolumab, Pembrolizumab and Axitinib or Avelumab and Axitinib) between 2015 and 2021 were analyzed. To examine the utility of irAEs as predictors of overall survival (OS) and progression-free survival (PFS), separate Kaplan–Meier analyses and Cox proportional regression analyses were applied. Landmark analysis was conducted after 12 weeks to reduce immortal time bias.

Result

irAEs were observed in 85 patients (63.4%). Cutaneous (n = 52, 38.8%), endocrine (n = 33, 24.6%) and hepatic (n = 19, 14.2%) irAEs were most commonly observed. In Kaplan–Meier analysis, patients experiencing irAEs showed favorable median PFS (15 months, 95% CI, 9.91-20.09) compared to the non-irAE group (5 months, 95% CI, 3.56-6.44, P < .001). The median OS was 25 months (95% CI, 16.79-33.21) in the non-irAE group, while it was not reached in the irAE group (P = .002). In multivariable analysis, the presence of any irAE was associated with favorable PFS (HR 0.46 [95% CI, 0.26-0.82] P = .008) and OS (HR: 0.28 [95% CI, 0.12-0.63] P = .002), respectively. Landmark analysis after 12 weeks showed mixed results depending on the classification of the irAE group at the landmark time.

Conclusion

The presence of irAEs under ICI therapy in patients with mRCC is associated with better PFS and OS. Thus, manageable irAEs should not be cause for premature discontinuation of ICI therapy, as they seem to indicate favorable outcomes.

Considering the time-dependent nature of irAEs is crucial estimating their value as predictive markers.

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免疫相关不良事件可预测接受免疫检查点抑制剂治疗的转移性肾细胞癌患者的无进展生存期和总生存期

背景使用抗 PD-1 / PD-L1 或 CTLA-4 免疫检查点抑制（ICI）的不同联合疗法被广泛用于转移性肾细胞癌（mRCC）患者。方法在这项回顾性队列研究中，分析了2015年至2021年间接受ICI治疗（Nivolumab、Ipilimumab和Nivolumab、Pembrolizumab和Axitinib或Avelumab和Axitinib）的134例mRCC患者的数据。为了研究irAEs作为总生存期（OS）和无进展生存期（PFS）预测指标的效用，分别采用了卡普兰-梅耶分析和Cox比例回归分析。地标分析在 12 周后进行，以减少不死时间偏差。最常观察到的是皮肤（52 例，占 38.8%）、内分泌（33 例，占 24.6%）和肝脏（19 例，占 14.2%）irAEs。在卡普兰-梅耶尔分析中，与无虹膜不良反应组（5 个月，95% CI，3.56-6.44，P < .001）相比，出现虹膜不良反应的患者的中位 PFS（15 个月，95% CI，9.91-20.09）较好。非irAE组的中位OS为25个月（95% CI，16.79-33.21），而irAE组未达到这一水平（P = .002）。在多变量分析中，任何irAE的存在分别与良好的PFS（HR 0.46 [95% CI, 0.26-0.82] P = .008）和OS（HR：0.28 [95% CI, 0.12-0.63] P = .002）相关。12周后的地标分析结果不一，取决于地标时间的irAE组分类。因此，可控的虹膜睫状体异常不应成为过早终止 ICI 治疗的原因，因为它们似乎预示着良好的预后。考虑到虹膜睫状体异常的时间依赖性，对评估其作为预测指标的价值至关重要。

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.