Supplementary Material for: Prognostic Impact of Trial-Eligibility Criteria in Patients with Metastatic Renal Cell Carcinoma

<b><i>Objective:</i></b> 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). <b><i>Patients and Methods:</i></b> 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 &lt;70, hemoglobin &lt;9.0 g/dL, creatinine &gt;2.4 mg/dL (male) or &gt;2.0 mg/dL (female), calcium &gt;12.0 mg/dL, platelet &lt;100,000 /μL, neutrophil &lt;1,500 /μL, nonclear-cell histology, and brain metastasis. <b><i>Results:</i></b> 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, <i>p</i> &lt; 0.0001; OS: 13.8 vs. 43.4 months, <i>p</i> &lt; 0.0001). Objective response rate was also significantly lower in the trial-ineligible patients (15% vs. 37%, <i>p</i> = 0.0003). Multivariate analysis further showed that the trial-eligibility was an independent factor for PFS (hazard ratio [HR]: 2.46, <i>p</i> &lt; 0.0001) and OS (HR: 2.39, <i>p</i> &lt; 0.0001). In addition, the number of trial-ineligible factors were negatively correlated with PFS and OS. <b><i>Conclusions:</i></b> 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.

**研究目的**：本研究旨在评估临床试验入组标准对接受酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs）治疗的真实世界转移性肾细胞癌（metastatic renal cell carcinoma, mRCC）患者预后的影响。
**患者与方法**：本研究回顾性分析了以酪氨酸激酶抑制剂（TKIs）作为一线全身治疗方案的转移性肾细胞癌（mRCC）患者。若患者满足以下至少1项临床试验排除标准，则被判定为不符合入组条件：卡氏功能状态评分（Karnofsky performance status, KPS）<70分、血红蛋白<9.0 g/dL、肌酐>2.4 mg/dL（男性）或>2.0 mg/dL（女性）、血钙>12.0 mg/dL、血小板计数<100,000 /μL、中性粒细胞计数<1,500 /μL、非透明细胞组织学类型以及脑转移。
**结果**：本研究共纳入238例患者，其中101例（42%）被判定为不符合临床试验入组条件。酪氨酸激酶抑制剂启动治疗后的无进展生存期（progression-free survival, PFS）与总生存期（overall survival, OS）在不符合入组条件的患者中显著短于符合入组条件者：中位PFS分别为5.53个月与15.8个月（p<0.0001）；中位OS分别为13.8个月与43.4个月（p<0.0001）。不符合入组条件患者的客观缓解率（objective response rate, ORR）亦显著更低（15% vs. 37%，p=0.0003）。多因素分析进一步显示，临床试验入组资格是影响PFS（风险比[HR]=2.46，p<0.0001）与OS（HR=2.39，p<0.0001）的独立危险因素。此外，不符合入组条件的项目数量与PFS及OS呈负相关。
**结论**：在真实世界临床实践中，相当比例的转移性肾细胞癌（mRCC）患者不符合临床试验入组标准，且其治疗结局显著差于符合入组条件的患者。未来有必要开展针对免疫检查点抑制剂治疗时代真实世界中不符合入组条件患者结局的相关研究。