Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Firenze, Firenze, Italy.
Medical Oncology Unit, Ospedale San Paolo, Savona, Italy.
JAMA Netw Open. 2023 Nov 1;6(11):e2345185. doi: 10.1001/jamanetworkopen.2023.45185.
Low sodium levels have been associated with negative outcomes among patients with metastatic renal cell carcinoma (mRCC) receiving therapies other than immune checkpoint inhibitors (ICIs).
To investigate the role of natremia in patients with mRCC receiving nivolumab as a second-line or subsequent therapy.
DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, the clinical and biochemical data of patients with mRCC receiving nivolumab were collected from October 2015 to November 2019 as part of a multicenter Italian study. Data analysis was performed from February to March 2023.
Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks and, since May 2018, at a fixed dose of 240 mg every 2 weeks or 480 mg every 4 weeks. Patients were divided into 2 groups according to their median serum sodium value (<140 or ≥140 mEq/L).
The primary outcomes were the associations of pre-ICI and post-ICI sodium levels with overall survival (OS), progression-free survival (PFS), objective response rate, and disease control rate (DCR). The Kaplan-Meier method was used to estimate PFS and OS, and differences between groups were compared using the log-rank test.
A total of 401 patients with mRCC receiving nivolumab as second-line therapy were evaluated, and 355 eligible patients (median [range] age, 76 [44-84] years; 258 male patients [72.7%]) were included in the final cohort. Among patients with pre-ICI sodium greater than or equal to 140 mEq/L compared with those with sodium less than 140 mEq/L, the median PFS was 9.3 months (95% CI, 6.5-11.5 months) vs 7.4 months (95% CI, 4.6-10.1 months; P = .90), and the median OS was 29.2 months (95% CI, 21.8-35.9 months) vs 20.0 months (95% CI, 14.1-26.8 months; P = .03). Patients with post-ICI sodium values greater than or equal to 140 mEq/L had longer PFS (11.1 months [95% CI, 8.5-1.5 months] vs 5.1 months [95% CI, 4.1-7.5 months]; P = .01) and OS (32.9 months [95% CI, 25.1-42.6 months] vs 17.1 months [95% CI, 12.6-24.5 months]; P = .006) compared with patients with sodium values less than 140 mEq/L. Patients with both pre-ICI and post-ICI sodium values greater than or equal to 140 mEq/L exhibited a significant improvement in clinical outcomes compared with those with a value less than 140 mEq/L (PFS, 11.5 months [95% CI, 8.8-16.4 months] vs 5.8 months [95% CI, 4.4-8.3 months]; P = .008); OS, 37.6 months [95% CI, 29.0-49.9 months] vs 19.4 months [95% CI, 14.1-24.5 months]; P = .01). Moreover, sodium levels greater than or equal to 140 mEq/L were associated with significantly better DCR than lower sodium levels.
In this retrospective cohort study of patients with mRCC receiving nivolumab, sodium values greater than or equal to 140 mEq/L, both before and/or after ICI, were associated with better OS and PFS, as well as a higher DCR, compared with levels less than 140 mEq/L. These findings suggest that sodium levels may be associated with survival outcomes in patients with mRCC and may have potential use as variables to consider in patients' risk scores.
在接受免疫检查点抑制剂 (ICI) 以外的治疗的转移性肾细胞癌 (mRCC) 患者中，低钠水平与不良结局相关。
研究在接受纳武利尤单抗二线或后续治疗的 mRCC 患者中，血钠水平的作用。
设计、地点和参与者：在这项回顾性队列研究中，从 2015 年 10 月至 2019 年 11 月，从接受纳武利尤单抗治疗的 mRCC 患者的多中心意大利研究中收集了临床和生化数据。数据分析于 2023 年 2 月至 3 月进行。
纳武利尤单抗静脉输注，剂量为 3mg/kg，每 2 周一次，自 2018 年 5 月起，剂量固定为每 2 周 240mg 或每 4 周 480mg。根据患者的中位血清钠值(<140 或≥140mEq/L)将其分为 2 组。
主要结局是 ICI 前和 ICI 后钠水平与总生存期 (OS)、无进展生存期 (PFS)、客观缓解率和疾病控制率 (DCR) 的相关性。使用 Kaplan-Meier 方法估计 PFS 和 OS，并使用对数秩检验比较组间差异。
共评估了 401 例接受纳武利尤单抗二线治疗的 mRCC 患者，最终队列纳入了 355 例符合条件的患者(中位[范围]年龄，76[44-84]岁；男性 258 例[72.7%])。与钠值小于 140mEq/L 的患者相比，钠值大于或等于 140mEq/L 的患者的中位 PFS 为 9.3 个月(95%CI，6.5-11.5 个月)和 7.4 个月(95%CI，4.6-10.1 个月；P=0.90)，中位 OS 为 29.2 个月(95%CI，21.8-35.9 个月)和 20.0 个月(95%CI，14.1-26.8 个月；P=0.03)。钠值大于或等于 140mEq/L 的患者的 ICI 后 PFS 更长(11.1 个月[95%CI，8.5-1.5 个月] vs 5.1 个月[95%CI，4.1-7.5 个月]；P=0.01)，OS 更长(32.9 个月[95%CI，25.1-42.6 个月] vs 17.1 个月[95%CI，12.6-24.5 个月]；P=0.006)，与钠值小于 140mEq/L 的患者相比。与钠值小于 140mEq/L 的患者相比，ICI 前和 ICI 后钠值大于或等于 140mEq/L 的患者的临床结局有显著改善(PFS，11.5 个月[95%CI，8.8-16.4 个月] vs 5.8 个月[95%CI，4.4-8.3 个月]；P=0.008)；OS，37.6 个月[95%CI，29.0-49.9 个月] vs 19.4 个月[95%CI，14.1-24.5 个月]；P=0.01)。此外，与较低的血钠水平相比，血钠水平大于或等于 140mEq/L 与更好的 DCR 显著相关。
在这项接受纳武利尤单抗二线或后续治疗的 mRCC 患者的回顾性队列研究中，与钠值小于 140mEq/L 的患者相比，ICI 前和/或后钠值大于或等于 140mEq/L 与更好的 OS 和 PFS 相关，以及更高的 DCR。这些发现表明，钠水平可能与 mRCC 患者的生存结局相关，并可能作为患者风险评分中考虑的变量。
