A multicenter randomized phase II trial of lenvatinib plus everolimus versus cabozantinib in patients with metastatic clear-cell RCC that progressed on PD-1 immune checkpoint inhibition (LenCabo).

Upon progression, common options include cabozantinib or lenvatinib + everolimus, although these regimens have never been directly compared.

在疾病进展后，常见的选择包括卡博替尼或仑伐替尼+依维莫司，尽管这些方案从未直接比较过。

We hypothesized that lenvatinib + everolimus will improve progression-free survival(PFS) compared with cabozantinib after progression on PD-1 ICI.

我们假设仑伐替尼联合依维莫司在PD-1免疫检查点抑制剂（ICI）治疗进展后，与卡博替尼相比，能够改善无进展生存期（PFS）。

patients_and_methods

This multicenter, randomized phase II trial enrolled patients with metastatic ccRCC previously treated with one to two lines including PD-1 ICI.

这项多中心、随机化II期临床试验招募了先前接受过一至两线治疗，包括PD-1 ICI治疗的转移性透明细胞肾细胞癌（ccRCC）患者。

Participants received lenvatinib 18 mg/day + everolimus 5 mg/day versus cabozantinib 60 mg/day, stratified by International Metastatic RCC Database Consortium risk group and prior TT.

参与者接受仑伐替尼18 mg/天 + 依维莫司5 mg/天与卡博替尼60 mg/天治疗，按国际转移性肾细胞癌数据库联盟风险组和先前的靶向治疗进行分层。

A Bayesian optimal phase II design was used.

采用了贝叶斯最优二期设计。

Results

In total 90 patients were randomized; 86 patients received at least one dose of assigned lenvatinib + everolimus (n = 40) or cabozantinib (n = 46).

共有90名患者被随机分配；86名患者至少接受了一剂指定的仑伐替尼+依维莫司(n=40)或卡博替尼(n=46)。

Median time from randomization to data cut-off date (1 August 2025) was 20 months (interquartile range 14.9-22.5 months).

从随机分配到数据截止日期（2025年8月1日）的中位时间是20个月（四分位数范围14.9-22.5个月）。

A total of 60 PFS events were observed.

共观察到60例无进展生存（PFS）事件。

Median PFS was 15.7 months with lenvatinib + everolimus and 10.2 months with cabozantinib [hazard ratio0.51, 95% confidence interval(CI) 0.29-0.89, P = 0.02].

lenvatinib联合everolimus的中位无进展生存期（PFS）为15.7个月，而cabozantinib为10.2个月[风险比0.51，95%置信区间（CI）0.29-0.89，P = 0.02]。

The objective response ratewas 52.6% with lenvatinib + everolimus and 38.6% with cabozantinib.

客观缓解率为52.6%的仑伐替尼+依维莫司组和38.6%的卡博替尼组。

Overall survival(OS) data were immature and inconclusive due to a low number of events (n = 24/86; 1-year OS probability 87.0% versus 84.6% [95% CI 0.47% to 2.38%] with lenvatinib + everolimus versus cabozantinib, respectively.

由于事件数量较少（n=24/86），总生存（OS）数据尚不成熟且结论不明确（仑伐替尼+依维莫司组1年生存概率为87.0%，卡博替尼组为84.6%，95%置信区间为0.47%至2.38%）。

Discontinuation rates due to toxicity were 20% with lenvatinib + everolimus and 10.9% with cabozantinib.

由于毒性导致的停药率，lenvatinib + everolimus组为20%，cabozantinib组为10.9%。

Conclusions

In this randomized phase II trial in metastatic ccRCC that progressed on prior PD-1 ICIs, lenvatinib + everolimus significantly prolonged PFS over cabozantinib.

在这项针对既往PD-1 ICIs治疗后进展的转移性ccRCC的随机II期试验中，lenvatinib + everolimus显著延长了无进展生存期（PFS），超过了cabozantinib。

As the first head-to-head comparison of contemporary second-line or later treatments after ICI, these results are relevant to treatment sequencing and inform oncology practice.

作为首次对ICI治疗后当代二线或更晚治疗方案的直接比较，这些结果对于治疗序列选择具有相关性，并为肿瘤学实践提供了信息。