Background

Immunotherapy has brought clinical benefits to patients with metastatic renal cell cancer (mRCC). Most patients tolerate immunotherapy but serious immune-related adverse events (irAEs) have been reported. Some studies indicate a correlation between irAEs and clinical response in other cancer types (eg, lung cancer and melanoma). For patients with mRCC, the impact of irAE on clinical outcome is unknown.

Patients and Methods

A retrospective review of 167 patients with mRCC treated with nivolumab as standard of care between March 2017 and January 2018 in 16 Italian centers was performed. irAEs were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0.

Results

Any grade and grade 3/4 irAEs occurred in 46% and 8.9% of patients, respectively. The median time to appearance of irAEs was 10 weeks; 38.8% of patients required steroid treatment. The most common irAEs were cutaneous (33.7%) and gastrointestinal (23.3%). The median overall survival and progression-free survival were 20.13 and 7.86 months, respectively. Patients with irAEs showed a greater overall survival (hazard ratio, 0.38; 95% confidence interval [CI], 0.23-0.63) and progression-free survival (hazard ratio, 0.44; 95% CI, 0.29-0.66) benefit as well as better overall response rate (27.3% vs. 13.7%; odds ratio, 2.36; 95% CI, 1.03-5.44) and disease control rate (68.8% vs. 48%; odds ratio, 2.4; 95% CI, 1.23-4.67) if compared with those without irAEs. No correlation was found between steroid use and clinical outcomes.

Conclusions

Our analysis revealed that the appearance of irAEs was associated with better outcomes in patients treated with nivolumab. This data may be limited by sample size and the retrospective nature of the study.

中文翻译：

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使用 Nivolumab 治疗的转移性肾细胞癌 (mRCC) 患者的免疫相关不良事件 (IRAE) 发生与临床结果之间的相关性：IRAENE 试验，一项意大利多机构回顾性研究。

背景

免疫疗法为转移性肾细胞癌（mRCC）患者带来了临床益处。大多数患者耐受免疫治疗，但已报告了严重的免疫相关不良事件 (irAE)。一些研究表明 irAE 与其他癌症类型（例如肺癌和黑色素瘤）的临床反应之间存在相关性。对于 mRCC 患者，irAE 对临床结果的影响尚不清楚。

患者和方法

对 2017 年 3 月至 2018 年 1 月期间在意大利 16 个中心接受纳武利尤单抗治疗的 167 名 mRCC 患者进行了回顾性研究。irAE 使用不良事件通用术语标准 (CTCAE) v.4.0 进行评估。

结果

任何级别和 3/4 级 irAE 分别发生在 46% 和 8.9% 的患者中。出现 irAE 的中位时间为 10 周；38.8% 的患者需要类固醇治疗。最常见的 irAE 是皮肤 (33.7%) 和胃肠道 (23.3%)。中位总生存期和无进展生存期分别为 20.13 个月和 7.86 个月。患有 irAEs 的患者显示出更大的总生存期（风险比，0.38；95% 置信区间 [CI]，0.23-0.63）和无进展生存期（风险比，0.44；95% CI，0.29-0.66）以及更好的获益总体缓解率（27.3% 对 13.7%；优势比，2.36；95% CI，1.03-5.44）和疾病控制率（68.8% 对 48%；优势比，2.4；95% CI，1.23-4.67）如果与没有 irAE 的人相比。在类固醇使用和临床结果之间没有发现相关性。

结论

我们的分析显示，irAE 的出现与接受 nivolumab 治疗的患者的更好结果相关。该数据可能受到样本量和研究回顾性的限制。