系统治疗和肾细胞癌原发肿瘤缩小：抗血管生成和免疫检查点抑制方案的真实世界比较。
Systemic therapies and primary tumour downsizing in renal cell carcinoma: a real-world comparison of anti-angiogenic and immune checkpoint inhibition regimens.
机构信息
Barts Health NHS Trust, St Bartholomew's Hospital, West Smithfield, London, UK.
Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, UK.
出版信息
World J Urol. 2024 Jul 24;42(1):442. doi: 10.1007/s00345-024-05133-8.
PURPOSE
To investigate responses in the primary tumour to different systemic treatment regimens in patients with metastatic renal cell carcinoma (mRCC).
METHODS
A single-centre retrospective analysis of treatment-naive mRCC patients without prior nephrectomy receiving VEGF tyrosine kinase inhibitors (VEGF only), immune checkpoint inhibitors (IO only), or combinations thereof (IO + VEGF). The primary outcome was the rate of partial response in the primary tumour (primary tumour PR, ≥ 30% diameter reduction). Secondary outcomes were time to best primary tumour diameter change, overall survival (OS) and progression-free survival (PFS) by Kaplan-Meier analysis. Predictors of survival outcomes were explored by Cox proportional hazards regression analysis.
RESULTS
The rate of primary tumour PR was 14% for VEGF only (4/28 patients), 22% for IO only (5/23) and 50% for IO + VEGF (7/14), with median best primary tumour diameter change of - 8.0%, + 5.1%, and - 31.1% respectively, and median time to best primary tumour diameter change of 3.2, 3.0 and 6.9 months respectively. Median OS was significantly greater with IO + VEGF compared to VEGF only (HR 0.45, p = 0.04) and non-significantly greater compared to IO only (HR 0.46, p = 0.06). In multivariable analysis, primary tumour PR was the only response variable significantly associated with both OS (adjusted HR 0.32, p = 0.01) and PFS (adjusted HR 0.29, p < 0.01).
CONCLUSION
mRCC patients without prior nephrectomy receiving first-line IO + VEGF regimens showed the greatest primary tumour responses, suggesting further prospective evaluation of this combination in the neoadjuvant and deferred cytoreductive nephrectomy settings.
目的
研究转移性肾细胞癌（mRCC）患者在接受不同全身治疗方案时原发肿瘤的反应。
方法
对未接受过肾切除术的初治 mRCC 患者进行单中心回顾性分析，这些患者未接受过先前的治疗，包括接受血管内皮生长因子酪氨酸激酶抑制剂（VEGF 仅）、免疫检查点抑制剂（IO 仅）或两者联合治疗（IO+VEGF）。主要结局是原发肿瘤的部分缓解率（原发肿瘤 PR，直径减少≥30%）。次要结局是通过 Kaplan-Meier 分析评估最佳原发肿瘤直径变化时间、总生存期（OS）和无进展生存期（PFS）。通过 Cox 比例风险回归分析探讨生存结局的预测因素。
结果
VEGF 仅组的原发肿瘤 PR 率为 14%（28 例患者中有 4 例），IO 仅组为 22%（23 例中有 5 例），IO+VEGF 组为 50%（14 例中有 7 例），最佳原发肿瘤直径变化的中位数分别为-8.0%、+5.1%和-31.1%，最佳原发肿瘤直径变化的中位数时间分别为 3.2、3.0 和 6.9 个月。与 VEGF 仅组相比，IO+VEGF 组的中位 OS 显著延长（HR 0.45，p=0.04），与 IO 仅组相比无显著差异（HR 0.46，p=0.06）。多变量分析显示，原发肿瘤 PR 是唯一与 OS（调整后的 HR 0.32，p=0.01）和 PFS（调整后的 HR 0.29，p<0.01）均显著相关的反应变量。
结论
未接受过肾切除术的一线 IO+VEGF 方案治疗的 mRCC 患者显示出最大的原发肿瘤反应，这表明进一步在新辅助和延迟细胞减灭性肾切除术环境中评估这种联合治疗的前瞻性研究是必要的。
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