免疫检查点抑制剂时代的细胞减灭性肾切除术：美国食品和药物管理局的汇总分析。
Cytoreductive nephrectomy in the era of immune checkpoint inhibitors: a US Food and Drug Administration pooled analysis.
机构信息
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Oncology Center of Excellence, US Food and Drug Administration, Silver Spring, MD, USA.
出版信息
J Natl Cancer Inst. 2024 Jul 1;116(7):1043-1050. doi: 10.1093/jnci/djae066.
BACKGROUND
This pooled analysis of patient-level data from trials evaluated the clinical outcomes of patients with metastatic renal cell carcinoma with or without cytoreductive nephrectomy before a combination of immune checkpoint inhibitor and antiangiogenic therapy.
METHODS
Data from 5 trials of immune checkpoint inhibitors plus antiangiogenic therapy were pooled. Only patients with stage 4 disease at initial diagnosis were included to ensure that nephrectomy was performed for cytoreductive purposes and not to previously treat an earlier stage of disease. The effect of cytoreductive nephrectomy before immune checkpoint inhibitor therapy on outcomes was evaluated using the Kaplan-Meier method and a Cox proportional hazards regression model, adjusted for age, sex, risk group, performance status, and the presence of sarcomatoid differentiation.
RESULTS
A total of 981 patients were included. The estimated median progression-free survival with and without nephrectomy was 15 and 11 months, respectively; the adjusted hazard ratio was 0.71 (95% confidence interval = 0.59 to 0.85). The estimated median overall survival with and without nephrectomy was 46 and 28 months, respectively; the adjusted hazard ratio was 0.63 (95% confidence interval = 0.51 to 0.77). Objective response was 60% of patients with vs 46% of patients without cytoreductive nephrectomy.
CONCLUSIONS
Patients with metastatic renal cell carcinoma who undergo cytoreductive nephrectomy before immune checkpoint inhibitor plus antiangiogenic therapy had improved outcomes compared with patients without cytoreductive nephrectomy. Selection factors for cytoreductive nephrectomy may be prognostic and could not be fully controlled for in this retrospective analysis. Prospective determination of and stratification by prior cytoreductive nephrectomy may be considered when designing clinical trials to assess the impact of this factor on prognosis.
背景
本项汇总分析评估了转移性肾细胞癌患者在接受免疫检查点抑制剂联合抗血管生成治疗前接受或不接受肾切除术的临床结局，这些患者的入组数据来自于临床试验。
方法
对免疫检查点抑制剂联合抗血管生成治疗的 5 项临床试验的数据进行汇总。仅纳入初始诊断为 4 期疾病的患者，以确保肾切除术是出于减瘤目的，而不是用于治疗更早阶段的疾病。采用 Kaplan-Meier 法和 Cox 比例风险回归模型，对免疫检查点抑制剂治疗前肾切除术对结局的影响进行评估，调整因素包括年龄、性别、风险分组、体能状态和肉瘤样分化的存在。
结果
共纳入 981 例患者。有或无肾切除术的中位无进展生存期分别为 15 个月和 11 个月；调整后的风险比为 0.71（95%置信区间为 0.59 至 0.85）。有或无肾切除术的中位总生存期分别为 46 个月和 28 个月；调整后的风险比为 0.63（95%置信区间为 0.51 至 0.77）。肾切除术组的客观缓解率为 60%，而无肾切除术组为 46%。
结论
与未行肾切除术的患者相比，在接受免疫检查点抑制剂联合抗血管生成治疗前接受肾切除术的转移性肾细胞癌患者的结局得到改善。肾切除术的选择因素可能具有预后意义，在本回顾性分析中无法完全控制这些因素。在设计临床试验评估该因素对预后的影响时，可能需要考虑对先前进行的肾切除术进行前瞻性确定和分层。
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