First-line benmelstobart plus anlotinib versus sunitinib in advanced renal cell carcinoma (ETER100): a multicentre, randomised, open-label, phase 3 trial.

This trial aimed to compare benmelstobart (a novel PD-L1 inhibitor) plus anlotinib with sunitinib as first-line treatment for advanced renal cell carcinoma.

该试验旨在比较新型PD-L1抑制剂贝美洛替布（benmelstobart）联合阿诺替尼与舒尼替尼作为晚期肾细胞癌的一线治疗。

Methods

ETER100 was a multicentre, randomised, open-label, phase 3 trial conducted at 37 medical sites in China.

ETER100 是在中国 37 个医疗机构进行的多中心、随机、开放标签、III 期试验。

We included patients aged 18-80 years, who had previously untreated, advanced, clear-cell renal cell carcinoma, and an Eastern Cooperative Oncology Group performance status of 0 or 1.

我们纳入了年龄在 18-80 岁之间，之前未接受过治疗，患有晚期透明细胞肾细胞癌，且东部肿瘤协作组表现状态为 0 或 1 的患者。

We randomly assigned (1:1) patients to receive either benmelstobart (intravenous, 1200 mg, once every 3 weeks) plus anlotinib (oral, 12 mg, once daily for the first 2 weeks of a 3-week cycle) or sunitinib (oral, 50 mg, once daily for the first 4 weeks of a 6-week cycle) until disease progression, unacceptable toxicity, investigator's decision, or patient withdrawal. Randomisation was done centrally with stratified block randomisation (block size 4) and stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk.

我们以1:1的比例随机分配患者接受贝美替尼（静脉注射，1200毫克，每3周一次）加安罗替尼（口服，12毫克，每3周周期的前2周每日一次）或舒尼替尼（口服，50毫克，每6周周期的前4周每日一次），直到疾病进展、不可接受的毒性、研究者决定或患者撤回。随机化是通过中心进行的分层区组随机化（区组大小为4），并根据国际转移性肾细胞癌数据库联盟风险进行分层。

The primary endpoint was progression-free survivalas assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumours version 1.1 in the full analysis set (ie, randomly assigned patients who received at least one dose of study drug without the violation of key inclusion criteria) and per-protocol set (ie, randomly assigned patients who received at least one cycle of protocol treatment without major protocol violations and had at least one efficacy assessment).

主要终点是根据实体瘤疗效评价标准1.1版本，通过盲法独立中央审查评估的无进展生存期，在全分析集（即至少接受一次研究药物剂量且未违反关键纳入标准的随机分配患者）和按方案集（即至少接受一个周期的方案治疗且无重大方案违规并至少进行了一次疗效评估的随机分配患者）中进行评估。

In this Article, we report the results of a prespecified interim analysis.

在这篇文章中，我们报告了预先设定的中期分析结果。

This ongoing study, closed to recruitment, is registered with ClinicalTrials.gov, NCT04523272.

这项正在进行的研究已经停止招募，已在ClinicalTrials.gov注册，注册号为NCT04523272。

Results

Between Aug 25, 2020, and Feb 6, 2023, we assessed 687 patients for eligibility, 531 (77%) of whom were randomly assigned to receive either benmelstobart plus anlotinib (266 [50%] patients) or sunitinib (265 [50%] patients). 527 (99%) patients were included in the full analysis set (263 [50%] patients who received benmelstobart plus anlotinib and 264 [50%] who received sunitinib).

在2020年8月25日至2023年2月6日期间，我们评估了687名患者的资格，其中531名（77%）被随机分配接受benmelstobart联合anlotinib治疗（266名[50%]患者）或sunitinib治疗（265名[50%]患者）。527名（99%）患者被纳入全分析集（263名[50%]接受benmelstobart联合anlotinib治疗的患者和264名[50%]接受sunitinib治疗的患者）。

All patients were Chinese (400 [76%] men and 127 [24%] women), with a median age of 60 years (IQR 54-67).

所有患者均为中国籍（男性400名[76%]，女性127名[24%]），中位年龄为60岁（四分位数间距54-67岁）。

As of the cutoff date (Jan 31, 2024), the median follow-up was 22·8 months (IQR 15·2-29·7).

截至截止日期（2024年1月31日），中位随访时间为22.8个月（四分位数间距15.2-29.7）。

In the full analysis set, median progression-free survivalwas significantly longer with benmelstobart plus anlotinib than with sunitinib (19·0 months [95% CI 15·3-22·8] vs 9·8 months [8·4-12·4]; hazard ratio[HR] 0·53 [95% CI 0·42-0·67]; p<0·0001).

在完整分析集中，与舒尼替尼相比，苯美司托巴特联合安罗替尼的中位无进展生存期显著更长（19.0个月 [95% 置信区间 15.3-22.8] 对比 9.8个月 [8.4-12.4]；风险比 [HR] 0.53 [95% 置信区间 0.42-0.67]；p<0.0001）。

In the per-protocol set, median progression-free survivalwas 19·0 months (16·5-22·8) in the benmelstobart-anlotinib group versus 11·0 months (8·5-13·6) in the sunitinib group (HR 0·55 [0·43-0·70]; p<0·0001).

在按方案集分析中，benmelstobart-anlotinib组的中位无进展生存期为19.0个月（16.5-22.8），而sunitinib组为11.0个月（8.5-13.6）（HR 0.55 [0.43-0.70]；p<0.0001）。

The most common grade 3 or worse treatment-related adverse eventwas hypertension (occurring in 91 [34%] of 264 patients in the benmelstobart-anlotinib group vs 55 [21%] of 264 in the sunitinib group).

最常见的3级或更严重的治疗相关不良事件是高血压，benmelstobart-anlotinib组有91例（264名患者中的34%），而sunitinib组有55例（264名患者中的21%）。

Serious treatment-related adverse events occurred in 63 (24%) patients in the benmelstobart-anlotinib group and in 42 (16%) patients in the sunitinib group.

在使用贝美替尼-阿诺替尼组的63名（24%）患者和使用舒尼替尼组的42名（16%）患者中，发生了严重的治疗相关不良事件。

In the benmelstobart-anlotinib group, three (1%) deaths occurred due to treatment-related adverse events (one each with cardiac-respiratory arrest, unknown reason, and renal failure) and no deaths occurred in the sunitinib group.

在贝美替尼-阿诺替尼组中，有三名（1%）患者因治疗相关不良事件死亡（各有心脏呼吸骤停、不明原因和肾衰竭各一例），而在舒尼替尼组中没有患者死亡。

interpretation

Benmelstobart plus anlotinib improved progression-free survivalcompared with sunitinib among patients with previously untreated, advanced clear-cell renal cell carcinoma.

在之前未接受治疗的晚期透明细胞肾细胞癌患者中，Benmelstobart联合阿诺替尼相较于舒尼替尼，改善了无进展生存期。

These findings suggest the potential of benmelstobart plus anlotinib as a treatment option for this population.

这些结果表明，Benmelstobart联合阿诺替尼作为这一人群的治疗选择具有潜在价值。

funding

Chia Tai Tianqing Pharmaceutical Group and CSCO Clinical Oncology Research Foundation.

正大天晴药业集团与中国临床肿瘤学会临床肿瘤研究基金会。

translation

For the Chinese translation of the abstract see Supplementary Materials section.

摘要的中文翻译请参见补充材料部分。