肿瘤收缩程度已被认为是晚期/转移性肾细胞癌（RCC）患者存活率的预测因素，这是一种历史上存活率很低的疾病。本研究旨在通过6个月肿瘤反应来进行总体生存期（OS）的初步分析，并评估特定亚组的疗效和生存结果。CLEAR是一项开放标签、多中心、随机、3期试验，旨在评估先线治疗晚期透明细胞肾癌。病人随机分为三组：口服利妥昔单抗20mg每日，静脉注射帕博利珠单抗200mg每3周；利妥昔联用依维莫司（不包括在这个分析中）；口服舒尼替尼50mg每天治疗4周/不治疗2周。我们进行了里程碑分析，评估了6个月内肿瘤缩小和进展疾病状态与OS的关系。以国际转移性肾细胞癌数据库联盟（IMDC）风险亚组和靶肾脏病变的存在为标准，分析无进展生存期、反应持续时间和客观反应率（ORR）。独立审查委员会根据实体瘤响应评价标准1.1评估了疗效。肿瘤收缩里程碑分析表明，口服利妥昔联用帕博利珠单抗治疗组的病人，在6个月内经确认有完全缓解或靶病变缩小超过75％的，24个月OS概率≥91.7％。根据疾病进展的里程碑分析表明，无进展病人在两组中死亡的概率较低。IMDC中级/差风险分类的患者用利妥昔联用帕博利珠单抗组与舒尼替尼组相比，无进展的中位无进展生存期较长（22.1 vs 5.9mo），ORR较高（72.4％vs28.8％）。类似地，IMDC有利的患者和有/没有靶肾脏病变的利妥昔联用帕博利珠单抗组的结果更好。这项研究的局限性是结果是探索性的，没有强制要求进行分类分析。口服利妥昔联用帕博利珠单抗与舒尼替尼相比，在晚期RCC患者中显示出更好的疗效；里程碑分析表明，在6个月的肿瘤反应与更长的OS有关。 在这份CLEAR试验的报告中，我们通过评估患者最初对治疗的反应来探讨晚期肾细胞癌患者的生存情况。我们还探讨了某些患者群体的整体治疗反应情况。根据口服利妥昔联用帕博利珠单抗治疗6个月后肿瘤缩小程度，患者比较完全缓解或靶病变缩小超过75％的病人比在6个月内肿瘤缩小程度更少的病人具有更好的生存率。此外，有更严重的疾病（根据国际转移性肾细胞癌数据库联盟）在开始研究治疗的患者，利妥昔联用帕博利珠单抗的无进展生存期比舒尼替尼更长。版权©2023 The Authors.由Elsevier B.V.出版，版权所有。

The extent of tumor shrinkage has been deemed a predictor of survival for advanced/metastatic renal cell carcinoma (RCC), a disease with historically poor survival.To perform an exploratory analysis of overall survival (OS) by tumor response by 6 mo, and to assess the efficacy and survival outcomes in specific subgroups.CLEAR was an open-label, multicenter, randomized, phase 3 trial of first-line treatment of advanced clear cell RCC.Patients were randomized 1:1:1 to lenvatinib 20 mg orally daily with pembrolizumab 200 mg intravenously once every 3 wk, lenvatinib plus everolimus (not included in this analysis), or sunitinib 50 mg orally daily for 4 wk on treatment/2 wk of no treatment.Landmark analyses were conducted to assess the association of OS with tumor shrinkage and progressive disease status by 6 mo. Progression-free survival, duration of response, and objective response rate (ORR) were analyzed by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk subgroup and by the presence of target kidney lesions. Efficacy was assessed by an independent review committee as per Response Evaluation Criteria in Solid Tumors version 1.1.Landmark analyses by tumor shrinkage showed that patients enrolled to lenvatinib plus pembrolizumab arm with a confirmed complete response or >75% target-lesion reduction by 6 mo had a 24-mo OS probability of ≥91.7%. A landmark analysis by disease progression showed that patients with no progression by 6 mo had lower probabilities of death in both arms. Patients with an IMDC risk classification of intermediate/poor had longer median progression-free survival (22.1 vs 5.9 mo) and a higher ORR (72.4% vs 28.8%) with lenvatinib plus pembrolizumab versus sunitinib. Similarly, results favored lenvatinib plus pembrolizumab in IMDC-favorable patients and those with/without target kidney lesions. Limitations of the study are that results were exploratory and not powered/stratified.Lenvatinib plus pembrolizumab showed improved efficacy versus sunitinib for patients with advanced RCC; landmark analyses showed that tumor response by 6 mo correlated with longer OS.In this report of the CLEAR trial, we explored the survival of patients with advanced renal cell carcinoma by assessing how well they initially responded to treatment. We also explored how certain groups of patients responded to treatment overall. Patients were assigned to cycles of either lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 wk or sunitinib 50 mg daily for 4 wk (followed by a 2-wk break). Patients who either had a "complete response" or had their tumors shrunk by >75% within 6 mo after starting treatment with lenvatinib plus pembrolizumab had better survival than those with less tumor reduction by 6 mo. Additionally, patients who had more severe disease (as per the International Metastatic Renal Cell Carcinoma Database Consortium) at the start of study treatment survived for longer without disease progression with lenvatinib plus pembrolizumab than with sunitinib.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.