CABOSEQ 3—Comparison of Cabozantinib versus Sunitinib Following First-Line Nivolumab- Ipilimumab for Metastatic Renal Cell Carcinoma: A Target Trial Emulation Using Real-World Data from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)

IF 2.4 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer Pub Date : 2025-12-01 Epub Date: 2025-09-09 DOI:10.1016/j.clgc.2025.102431

Audreylie Lemelin , David Maj , Kosuke Takemura , Devon J. Boyne , Matthew T. Warkentin , Darren R. Brenner , Winson Y. Cheung , Connor Wells , Chris Labaki , Bradley A. McGregor , Luis Meza Contreras , Sumanta K. Pal , Benoit Beuselinck , Rana R. McKay , Bernadett Szabados , Thomas Powles , Takeshi Yuasa , Lisa Ludwig , Toni K. Choueiri , Daniel Y.C. Heng

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引用次数: 0

Abstract

Background and Objective

While the benefit of cabozantinib in metastatic renal cell carcinoma (mRCC) is well established post-tyrosine kinase inhibitor therapy, its comparative effectiveness versus sunitinib after first-line (1L) nivolumab-ipilimumab is uncertain.

Methods

A target trial emulation was designed using data from the IMDC to estimate the effect of second-line (2L) cabozantinib versus sunitinib within 18 months of discontinuing 1L nivolumab-ipilimumab on overall survival (OS). Patients diagnosed after January 1, 2017 were followed from initiation of 2L until death or last known contact. Inverse-probability of treatment weighting was used to adjust for hemoglobin, calcium, platelets, and neutrophils at 2L, Karnofsky performance score (KPS) at 2L, time from diagnosis to initiation of 2L, and response to 1L nivolumab-ipilimumab. Treatments were compared using adjusted Kaplan-Meier curves and adjusted hazard ratios (HR) from a Cox regression model. Missing data were addressed with multiple imputation by chained equations. E-values were used to assess the likelihood findings could be explained by residual confounding.

Key Findings and limitations

A total of 120 and 121 patients who received cabozantinib or sunitinib after 1L nivolumab-ipilimumab were included. The proportion with a KPS < 80% at 2L (21% vs. 46% P = .001) and the overall response rate to first line therapy (12.7% vs. 17.9% P = .002) differed significantly between cabozantinib and sunitinib. The objective response was 27% for cabozantinib versus 20% for sunitinib with a median time to treatment failure of 8.5 (95% CI: 6.9-12.9) and 4.5 (95% CI: 3.7-5.8) months. Median OS was 21.4 (95% CI: 17.9-NA) months from initiation of cabozantinib and 10.1 (95% CI: 7.6-17.7) months for sunitinib (Adjusted HR 0.44 (95% CI: 0.22-0.86)). The E-value was 2.92, suggesting a low likelihood of findings being due to residual confounding alone.

Conclusions

These data provide real-world evidence supporting cabozantinib as a second-line treatment option in mRCC following 1L nivolumab-ipilimumab.

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CABOSEQ 3：卡博赞替尼与舒尼替尼在一线纳沃单抗-伊匹单抗治疗转移性肾细胞癌的比较：使用国际转移性肾细胞癌数据库联盟（IMDC）的真实世界数据的靶试验模拟。

背景和目的：虽然卡博赞替尼在转移性肾细胞癌（mRCC）中的益处是公认的酪氨酸激酶抑制剂后治疗，但其与舒尼替尼在一线（1L）尼沃单抗-伊匹单抗后的比较有效性尚不确定。方法：利用IMDC的数据设计了一项靶试验模拟，以评估停药1L尼沃单抗-伊匹单抗后18个月内二线（2L）卡博赞替尼与舒尼替尼对总生存期（OS）的影响。2017年1月1日之后确诊的患者从开始感染2L到死亡或最后一次已知接触者进行随访。使用治疗加权的逆概率来调整2L时的血红蛋白、钙、血小板和中性粒细胞，2L时的Karnofsky性能评分（KPS），从诊断到开始2L的时间，以及1L纳鲁单抗-伊匹单抗的反应。采用校正Kaplan-Meier曲线和Cox回归模型的校正风险比（HR）对各处理进行比较。通过链式方程对缺失数据进行多次补全。e值用于评估剩余混淆解释结果的可能性。主要发现和局限性：共纳入120例和121例在1L尼沃单抗-伊匹单抗后接受卡博赞替尼或舒尼替尼的患者。卡博赞替尼和舒尼替尼在2L时KPS < 80%的比例（21%对46% P = .001）和一线治疗的总缓解率（12.7%对17.9% P = .002）差异显著。cabozantinib的客观缓解率为27%，而舒尼替尼为20%，治疗失败的中位时间为8.5个月（95% CI: 6.9-12.9）和4.5个月（95% CI: 3.7-5.8）。卡博替尼起始的中位OS为21.4个月（95% CI: 17.9-NA），舒尼替尼起始的中位OS为10.1个月（95% CI: 7.6-17.7）（调整后风险比0.44 (95% CI: 0.22-0.86)）。e值为2.92，表明结果仅由残留混杂引起的可能性很低。结论：这些数据提供了真实世界的证据，支持卡博赞替尼作为1L尼沃单抗-伊匹单抗后mRCC的二线治疗选择。

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.