Efficacy of cabozantinib and sunitinib for the treatment of intermediate/poor risk renal cell carcinoma based upon UK real-world data

D. Lee , G.J. Melendez-Torres , A. Challapalli , R. Frazer , J. McGrane , A. Bahl
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Abstract

Background

The purpose of this study was to explore the effectiveness of cabozantinib versus sunitinib for the treatment of first-line metastatic renal cell carcinoma in intermediate/poor risk patients.

Materials and methods

Retrospective review of cases between 1 January 2018 and 30 June 2021 across 17 UK centres. Univariable and multivariable Cox proportional hazards modelling to identify prognostic factors. Inverse probability of treatment weighting, to estimate the causal effect of first-line treatment type.

Results

Cabozantinib patients (n = 106) had poorer risk status, less prior nephrectomy, shorter time to therapy, and more clear cell histology than sunitinib patients (n = 218). More sunitinib patients received a second or third line of subsequent treatment (56% and 23% versus 43% and 13%). Though there was no significant difference between treatments in overall survival (OS) or progression-free survival (PFS) across models, the difference in PFS bordered on significant in a multipredictor analysis (benefit in favour of cabozantinib; P = 0.06). When the Kaplan–Meier curves were stratified by risk status (intermediate versus poor), patients had similar OS within the risk groups. PFS appeared to differ with poor risk patients performing better on cabozantinib. Inverse probability of treatment weighting analysis showed little difference from the unadjusted results: OS hazard ratio = 1.119 (95% confidence interval (CI) 0.823-1.521); PFS hazard ratio 0.825 (95% CI 0.636-1.070) for cabozantinib versus sunitinib.

Conclusions

Our results showed no significant difference in either OS or PFS between treatments. Cabozantinib trended towards improved PFS and reduced OS. Decision-making for tyrosine kinase inhibitor monotherapy should consider later-line treatment options. This analysis is of particular relevance as sunitinib is now off-patent meaning that the cost of a course of treatment has considerably reduced.
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基于英国真实世界数据的卡博替尼和舒尼替尼治疗中危/低危肾细胞癌的疗效
背景本研究旨在探讨卡博替尼对舒尼替尼治疗中危/低危患者一线转移性肾细胞癌的有效性。采用单变量和多变量 Cox 比例危险度模型确定预后因素。结果与舒尼替尼患者(n = 218)相比,卡博赞替尼患者(n = 106)的风险状况更差、既往肾切除术更少、治疗时间更短、透明细胞组织学更多。接受二线或三线后续治疗的舒尼替尼患者更多(56% 和 23% 对 43% 和 13%)。虽然不同治疗方法在总生存期(OS)或无进展生存期(PFS)方面没有显著差异,但在多预测因子分析中,PFS的差异接近显著(卡博赞替尼获益;P = 0.06)。当 Kaplan-Meier 曲线按风险状态(中度风险与重度风险)分层时,各风险组患者的 OS 相似。PFS似乎存在差异,风险较低的患者使用卡博替尼后表现更好。治疗的逆概率加权分析显示,与未调整的结果差别不大:卡博替尼对舒尼替尼的OS危险比=1.119(95%置信区间(CI)0.823-1.521);PFS危险比0.825(95% CI 0.636-1.070)。卡博替尼有改善 PFS 和降低 OS 的趋势。酪氨酸激酶抑制剂单药治疗的决策应考虑晚期治疗方案。由于舒尼替尼目前已过专利期,这意味着一个疗程的费用已大大降低,因此这项分析具有特别重要的意义。
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