Comparisons of Pembrolizumab Plus Lenvatinib, Nivolumab Plus Cabozantinib, and Cabozantinib Monotherapy in Advanced Non-Clear Cell Renal Cell Carcinoma Based on Individual Patient Data Reconstruction

IF 2.4 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer Pub Date : 2025-12-01 Epub Date: 2025-10-15 DOI:10.1016/j.clgc.2025.102458

Wei Chen , Hajime Tanaka , Soichiro Yoshida , Shunya Matsumoto , Masaki Kobayashi , Shohei Fukuda , Hiroshi Fukushima , Yuma Waseda , Yasuhisa Fujii

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Abstract

Introduction

The optimal treatment strategy for advanced non-clear cell renal cell carcinoma (nccRCC) remains unclear. This study compares the efficacy of pembrolizumab plus lenvatinib (Pem+Len), nivolumab plus cabozantinib (Nivo+Cabo), and cabozantinib monotherapy (Cabo) for advanced nccRCC.

Patients and Methods

A systematic literature search was conducted to identify clinical trials investigating the 3 treatment regimens for advanced nccRCC. Individual patient data (IPD) were reconstructed from Kaplan–Meier curves for progression-free survival (PFS) and overall survival (OS) using the IPDfromKM package. The outcomes were compared across treatment regimens. A subgroup analysis was conducted for papillary RCC (pRCC).

Results

Three clinical trials (NCT02761057, NCT03635892, and NCT04704219) were included; 242 patients were analyzed, including 158/40/44 patients receiving Pem+Len/Nivo+Cabo/Cabo, respectively. Patients with pRCC accounted for 59%/80%/100% of each treatment cohort, respectively. Pem+Len yielded significantly superior PFS (HR = 0.52, 95% CI, 0.34-0.81, P < .01) and OS (HR = 0.50, 95% CI, 0.28-0.89, P = .02) compared with Cabo. Nivo+Cabo showed potential superiority over Cabo in PFS (HR = 0.73, 95% CI, 0.44-1.20, P = .21) and OS (HR = 0.64, 95% CI, 0.35-1.16, P = .14), although these differences did not reach statistical significance. Our analysis did not reveal a clear superiority/inferiority between Pem+Len and Nivo+Cabo. The subgroup analysis for pRCC demonstrated significantly better PFS with Pem+Len (HR = 0.48, 95% CI, 0.29-0.77, P < .01) compared with Cabo, while the benefit of Nivo+Cabo was not significant (HR = 0.66, 95% CI, 0.37-1.15, P = .14). Limitations included its retrospective design and inconsistent follow-up periods among the trials.

Conclusions

The IPD reconstruction analysis suggested better PFS and OS with Pem+Len and Nivo+Cabo compared with Cabo, supporting the use of these combination therapies for advanced nccRCC. Further comparative studies are needed to validate these findings.

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基于个体患者数据重建的Pembrolizumab + Lenvatinib， Nivolumab + Cabozantinib和Cabozantinib单药治疗晚期非透明细胞肾细胞癌的比较

晚期非透明细胞肾细胞癌（nccRCC）的最佳治疗策略尚不清楚。本研究比较了派姆单抗联合lenvatinib （Pem+Len）、nivolumab联合cabozantinib （Nivo+Cabo）和cabozantinib单药治疗晚期nccRCC的疗效。患者和方法：进行了系统的文献检索，以确定研究晚期nccRCC的3种治疗方案的临床试验。使用IPDfromKM包从Kaplan-Meier曲线重建无进展生存期（PFS）和总生存期（OS）的个体患者数据（IPD）。对不同治疗方案的结果进行比较。对乳头状RCC （pRCC）进行亚组分析。结果：纳入3项临床试验（NCT02761057、NCT03635892和NCT04704219）；共分析242例患者，其中Pem+Len/Nivo+Cabo/Cabo分别为158/40/44例。pRCC患者分别占每个治疗队列的59%/80%/100%。Pem+Len与Cabo相比，PFS （HR = 0.52, 95% CI, 0.34-0.81, P < 0.01）和OS （HR = 0.50, 95% CI, 0.28-0.89, P = 0.02）显著优于Cabo。Nivo+Cabo在PFS （HR = 0.73, 95% CI, 0.44-1.20, P = 0.21）和OS （HR = 0.64, 95% CI, 0.35-1.16, P = 0.14）方面有潜在优势，但差异无统计学意义。我们的分析并没有显示Pem+Len和Nivo+Cabo之间的明显优势/劣势。pRCC的亚组分析显示，Pem+Len的PFS明显优于Cabo (HR = 0.48, 95% CI, 0.29-0.77, P < 0.01)，而Nivo+Cabo的益处不显著（HR = 0.66, 95% CI, 0.37-1.15, P = 0.14）。局限性包括其回顾性设计和试验间随访期不一致。结论：IPD重建分析显示Pem+Len和Nivo+Cabo与Cabo相比有更好的PFS和OS，支持使用这些联合疗法治疗晚期nccRCC。需要进一步的比较研究来验证这些发现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical genitourinary cancer 医学-泌尿学与肾脏学

CiteScore

5.20

自引率

6.20%

发文量

201

审稿时长

54 days

期刊介绍： Clinical Genitourinary Cancer is a peer-reviewed journal that publishes original articles describing various aspects of clinical and translational research in genitourinary cancers. Clinical Genitourinary Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of genitourinary cancers. The main emphasis is on recent scientific developments in all areas related to genitourinary malignancies. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.