Background

Nivolumab showed an overall survival (OS) benefit in pretreated metastatic renal cell carcinoma (mRCC). The role of stereotactic body radiotherapy (SBRT) in mRCC remains to be defined.

Objective

Our aim was to evaluate the efficacy and safety of SBRT in combination with nivolumab in second- and third-line mRCC patients.

Design, setting, and participants

The NIVES study was a phase II, single-arm, multicenter trial in patients with mRCC with measurable metastatic sites who progressed after antiangiogenic therapy, of whom at least one was suitable for SBRT.

Intervention

The patients received SBRT to a lesion at a dose of 10 Gy in three fractions for 7 d from the first infusion of nivolumab. Nivolumab was given at an initial dose of 240 mg every 14 d for 6 mo and then 480 mg q4-weekly in responding patients.

Outcome measurements and statistical analysis

We hypothesized that nivolumab plus SBRT improves the objective response rate (ORR) compared with nivolumab alone from 25% (derived from historical controls) to 40%. Secondary endpoints were progression-free survival (PFS), OS, disease control rate (DCR) of irradiated and nonirradiated metastases, and safety.

Results and limitations

Sixty-nine patients were enrolled from July 2017 to March 2019. The ORR was 17% and the DCR was 55%. The median PFS was 5.6 mo (95% confidence interval [CI], 2.9–7.1) and median OS 20 mo (95% CI, 17–not reached). After 1.5 yr of follow-up, 23 patients died. The median time to treatment response was 2.8 mo and median duration of response was 14 mo. No new safety concerns arose.

Conclusions

We did not find sufficient evidence to suggest that nivolumab in combination with SBRT provides an added benefit in pretreated mRCC patients; it should however be evaluated in patients with oligometastatic or oligoprogressive disease.

Patient summary

Nivolumab in combination with stereotactic body radiotherapy does not provide evidence of increased outcomes in metastatic renal cell carcinoma patients. However this approach was safe and showed a good response of the irradiated lesions.

中文翻译：

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Nivolumab 联合立体定向放射治疗治疗转移性肾细胞癌患者。第二阶段 NIVES 研究的结果

背景

Nivolumab 在预处理的转移性肾细胞癌 (mRCC) 中显示出总生存期 (OS) 益处。立体定向放射治疗 (SBRT) 在 mRCC 中的作用仍有待确定。

客观的

我们的目的是评估 SBRT 联合 nivolumab 在二线和三线 mRCC 患者中的疗效和安全性。

设计、设置和参与者

NIVES 研究是一项 II 期、单臂、多中心试验，对象为具有可测量转移部位的 mRCC 患者，这些患者在抗血管生成治疗后出现进展，其中至少有一个适合 SBRT。

干涉

从第一次输注纳武利尤单抗起，患者接受 SBRT，剂量为 10 Gy，分三个部分，持续 7 天。Nivolumab 的初始剂量为每 14 天 240 毫克，持续 6 个月，然后在有反应的患者中每周 4 次 480 毫克。

结果测量和统计分析

我们假设与单独使用 nivolumab 相比，nivolumab 加 SBRT 可将客观缓解率 (ORR) 从 25%（来自历史对照）提高到 40%。次要终点是无进展生存期 (PFS)、OS、辐照和非辐照转移灶的疾病控制率 (DCR) 和安全性。

结果和局限性

2017 年 7 月至 2019 年 3 月共有 69 名患者入组。ORR 为 17%，DCR 为 55%。中位 PFS 为 5.6 个月（95% 置信区间 [CI]，2.9–7.1），中位 OS 为 20 个月（95% CI，17–未达到）。随访 1.5 年后，23 例患者死亡。中位治疗反应时间为 2.8 个月，中位反应持续时间为 14 个月。没有出现新的安全问题。

结论

我们没有找到足够的证据表明纳武利尤单抗与 SBRT 联用可为预先治疗的 mRCC 患者提供额外的益处；然而，它应该在患有寡转移或寡进展性疾病的患者中进行评估。

患者总结

纳武利尤单抗联合立体定向放射治疗并未提供转移性肾细胞癌患者预后增加的证据。然而，这种方法是安全的，并且显示出对辐照病变的良好反应。