Characterization of Responses to Lenvatinib plus Pembrolizumab in Patients with Advanced Renal Cell Carcinoma at the Final Prespecified Survival Analysis of the Phase 3 CLEAR Study

IF 25.3 1区医学 Q1 UROLOGY & NEPHROLOGY European urology Pub Date : 2024-04-06 DOI:10.1016/j.eururo.2024.03.015

Robert J. Motzer , Toni K. Choueiri , Thomas Hutson , Sun Young Rha , Javier Puente , Aly-Khan A. Lalani , Eric Winquist , Masatoshi Eto , Naveen S. Basappa , Nizar M. Tannir , Ulka Vaishampayan , Georg A. Bjarnason , Stéphane Oudard , Viktor Grünwald , Joseph Burgents , Ran Xie , Jodi McKenzie , Thomas Powles

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Abstract

In the phase 3 CLEAR trial, lenvatinib plus pembrolizumab (L + P) showed superior efficacy versus sunitinib in treatment-naïve patients with advanced renal cell carcinoma (aRCC). The combination treatment was associated with a robust objective response rate of 71%. Here we report tumor responses for patients in the L + P arm in CLEAR, with median follow-up of ∼4 yr at the final prespecified overall survival (OS) analysis. Tumor responses were assessed by independent review using Response Evaluation Criteria in Solid Tumors v1.1. Patients with a complete response (CR; n = 65), partial response (PR) with maximum tumor shrinkage ≥75% (near-CR; n = 59), or PR with maximum tumor shrinkage <75% (other PR; n = 129), were characterized in terms of their baseline characteristics. The median duration of response was 43.7 mo (95% confidence interval [CI] 39.2–not estimable) for the CR group, 30.5 mo (95% CI 22.4–not estimable) for the near-CR group, and 17.2 mo (95% CI 12.5–21.4) for the other PR group. The 36-mo OS rates were consistently high in the CR (97%), near-CR (86%), and other PR (62%) groups. Robust objective response rates were observed across International Metastatic RCC Database Consortium favorable-risk (69%, 95% CI 60–78%), intermediate-risk (73%, 95% CI 67–79%), and poor-risk (70%, 95% CI 54–85%) subgroups. The robust response to L + P supports this combination as a standard-of-care first-line treatment for patients with aRCC.

Patient summary

The CLEAR trial enrolled patients with advanced kidney cancer who had not previously received any treatment for their cancer. Here we report results for tumor shrinkage observed in the group that received lenvatinib plus pembrolizumab combination treatment during the trial. Shrinkage of target tumors with this combination was long-lasting and was observed in patients irrespective of their disease severity.

This trial is registered on ClinicalTrials.gov as NCT02811861.

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三期 CLEAR 研究最终预设生存期分析中，晚期肾细胞癌患者对伦伐替尼加 Pembrolizumab 治疗的反应特征。

在3期CLEAR试验中，来伐替尼加pembrolizumab（L+P）对治疗无效的晚期肾细胞癌（aRCC）患者的疗效优于舒尼替尼。联合治疗的客观反应率高达 71%。在此，我们报告了CLEAR中L+P治疗组患者的肿瘤应答情况，在最终的预设总生存期（OS）分析中，中位随访时间为4年。肿瘤反应采用实体瘤反应评估标准（Response Evaluation Criteria in Solid Tumors）v1.1进行独立审查评估。完全反应（CR；n = 65）、部分反应（PR）且肿瘤最大缩小率≥75%（近CR；n = 59）或部分反应（PR）且肿瘤最大缩小率<75%（其他PR；n = 129）的患者均具有基线特征。CR 组的中位反应持续时间为 43.7 个月（95% 置信区间 [CI] 39.2-无法估计），近 CR 组为 30.5 个月（95% CI 22.4-无法估计），其他 PR 组为 17.2 个月（95% CI 12.5-21.4）。CR 组（97%）、近 CR 组（86%）和其他 PR 组（62%）的 36 个月 OS 率一直很高。在国际转移性 RCC 数据库联盟的良险（69%，95% CI 60-78%）、中险（73%，95% CI 67-79%）和差险（70%，95% CI 54-85%）亚组中观察到了稳健的客观反应率。患者摘要CLEAR试验招募了既往未接受过任何治疗的晚期肾癌患者。在此，我们报告了试验期间接受来伐替尼加pembrolizumab联合治疗组的肿瘤缩小情况。无论患者的病情严重程度如何，这种联合疗法都能持久缩小靶向肿瘤。该试验已在ClinicalTrials.gov上注册，编号为NCT02811861。

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来源期刊

European urology 医学-泌尿学与肾脏学

CiteScore

43.00

自引率

2.60%

发文量

1753

审稿时长

23 days

期刊介绍： European Urology is a peer-reviewed journal that publishes original articles and reviews on a broad spectrum of urological issues. Covering topics such as oncology, impotence, infertility, pediatrics, lithiasis and endourology, the journal also highlights recent advances in techniques, instrumentation, surgery, and pediatric urology. This comprehensive approach provides readers with an in-depth guide to international developments in urology.