Supplementary Material for: Comparison of First-Line Anti-PD-1-Based Combination Therapies in Metastatic Renal-Cell Carcinoma: Real-World Experiences from a Retrospective, Multi-Institutional Cohort

<b><i>Introduction:</i></b> The aim of this study was to test for differences in overall (OS) and progression-free survival (PFS) rates and toxicity in first-line immune checkpoint inhibition (IO) combination therapy in metastatic renal-cell carcinoma (mRCC) patients. <b><i>Methods:</i></b> Between November 2017 and April 2021, 104 patients with histologically confirmed mRCC from 6 tertiary referral centers with either IO + IO (nivolumab + ipilimumab, <i>n</i> = 68) or IO + tyrosine kinase inhibitor (TKI) (pembrolizumab + axitinib, <i>n</i> = 36) were included. Kaplan-Meier and Cox regression analyses tested for OS and PFS differences. <b><i>Results:</i></b> Of 104 mRCC patients, 68 received IO + IO (65.4%) and 36 IO + TKI (34.6%) therapy, respectively. Median age was 67 years (interquartile range: 57–70.3). Patients receiving IO + TKI were less likely to be poor risk according to the International Metastatic Renal-Cell Carcinoma Database Consortium score (16.7 vs. 30.9%) and presented with lower T-stage, compared to IO + IO treated patients. Median PFS was 9.8 months (CI: 5.3–17.6) versus 12.3 months (CI: 7.7 – not reached) for IO + IO versus IO + TKI treatment, respectively (<i>p</i> = 0.22). Median OS was not reached, survival rates at 12 months being 73.9 versus 90.0% for IO + IO versus IO + TKI patients (<i>p</i> = 0.089). In subgroup analyses of elderly patients (≥70 years, <i>n</i> = 38), IO + TKI treatment resulted in better OS rates at 12 months compared to IO + IO (91.0 vs. 57.0%; <i>p</i> = 0.042). <b><i>Conclusion:</i></b> IO + IO and IO + TKI as first-line therapies in mRCC patients were both comparable as for the oncological outcome and toxicity.

<b><i>引言：</i></b> 本研究旨在探讨转移性肾细胞癌（metastatic renal-cell carcinoma, mRCC）患者一线免疫检查点抑制（immune checkpoint inhibition, IO）联合治疗方案的总生存期（overall survival, OS）、无进展生存期（progression-free survival, PFS）及毒性反应差异。
<b><i>方法：</i></b> 2017年11月至2021年4月，本研究纳入来自6家三级转诊中心、经组织学确认的104例mRCC患者，其中IO+IO方案组（纳武利尤单抗+伊匹木单抗，<i>n</i> = 68）与IO+酪氨酸激酶抑制剂（tyrosine kinase inhibitor, TKI）方案组（帕博利珠单抗+阿昔替尼，<i>n</i> = 36）各占比65.4%与34.6%。采用卡普兰-迈耶（Kaplan-Meier）分析法与考克斯回归（Cox regression）分析法评估OS与PFS的差异。
<b><i>结果：</i></b> 104例mRCC患者中，68例接受IO+IO方案治疗，36例接受IO+TKI方案治疗。受试者中位年龄为67岁（四分位距：57–70.3）。相较于IO+IO方案组，IO+TKI方案组患者按国际转移性肾细胞癌数据库联盟评分判定为不良风险的比例更低（16.7% vs. 30.9%），且T分期更早。IO+IO方案组与IO+TKI方案组的中位PFS分别为9.8个月（置信区间：5.3–17.6）与12.3个月（置信区间：7.7 – 未达到），组间差异无统计学意义（<i>p</i> = 0.22）。两组中位OS均未达到，IO+IO方案组与IO+TKI方案组患者的12个月生存率分别为73.9%与90.0%，组间差异无统计学意义（<i>p</i> = 0.089）。在老年患者（≥70岁，<i>n</i> = 38）的亚组分析中，IO+TKI方案组的12个月OS率显著高于IO+IO方案组（91.0% vs. 57.0%；<i>p</i> = 0.042）。
<b><i>结论：</i></b> 作为mRCC患者的一线治疗方案，IO+IO与IO+TKI联合治疗的肿瘤学结局与毒性反应均无显著差异。