Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
Department of Urology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
Urol Int. 2022;106(4):368-375. doi: 10.1159/000518162. Epub 2021 Aug 26.
The aim of the study was to evaluate the prognostic impact of trial-eligibility criteria on outcome in real-world metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs).
mRCC patients treated with TKIs as first-line systemic therapy were retrospectively evaluated. The patients were determined as trial-ineligible when they met at least 1 following trial-ineligible criteria; Karnofsky performance status score <70, hemoglobin <9.0 g/dL, creatinine >2.4 mg/dL (male) or >2.0 mg/dL (female), calcium >12.0 mg/dL, platelet <100,000 /μL, neutrophil <1,500 /μL, nonclear-cell histology, and brain metastasis.
Of 238 patients, 101 patients (42%) were determined as trial-ineligible. Progression-free survival (PFS) and overall survival (OS) after the TKI initiation were significantly shorter in the trial-ineligible patients than in the trial-eligible patients (median PFS: 5.53 vs. 15.8 months, p < 0.0001; OS: 13.8 vs. 43.4 months, p < 0.0001). Objective response rate was also significantly lower in the trial-ineligible patients (15% vs. 37%, p = 0.0003). Multivariate analysis further showed that the trial-eligibility was an independent factor for PFS (hazard ratio [HR]: 2.46, p < 0.0001) and OS (HR: 2.39, p < 0.0001). In addition, the number of trial-ineligible factors were negatively correlated with PFS and OS.
In real-word, the substantial number of mRCC patients did not meet the trial-eligibility criteria, and their outcome was worse than that in the trial-eligible patients. Further studies focusing on the outcome in real-world trial-ineligible patients in the immune checkpoint inhibitor era are warranted.
本研究旨在评估在接受酪氨酸激酶抑制剂（TKI）治疗的真实转移性肾细胞癌（mRCC）患者中，试验纳入标准对结局的预后影响。
回顾性评估接受 TKI 作为一线系统治疗的 mRCC 患者。当患者符合以下至少 1 项试验排除标准时，将其确定为不符合试验纳入标准：卡氏功能状态评分<70、血红蛋白<9.0g/dL、肌酐>2.4mg/dL（男性）或>2.0mg/dL（女性）、钙>12.0mg/dL、血小板<100,000/μL、中性粒细胞<1,500/μL、非透明细胞组织学和脑转移。
在 238 例患者中，101 例（42%）被确定为不符合试验纳入标准。与符合试验纳入标准的患者相比，不符合试验纳入标准的患者在 TKI 起始后的无进展生存期（PFS）和总生存期（OS）显著更短（中位 PFS：5.53 与 15.8 个月，p<0.0001；OS：13.8 与 43.4 个月，p<0.0001）。不符合试验纳入标准的患者客观缓解率也显著较低（15%与 37%，p=0.0003）。多变量分析进一步表明，试验纳入标准是 PFS（风险比[HR]：2.46，p<0.0001）和 OS（HR：2.39，p<0.0001）的独立因素。此外，不符合试验纳入标准的因素数量与 PFS 和 OS 呈负相关。
在真实世界中，大量 mRCC 患者不符合试验纳入标准，其结局较符合试验纳入标准的患者更差。需要进一步研究免疫检查点抑制剂时代真实世界中不符合试验纳入标准患者的结局。
