Background

The standard of care for locoregional renal cell carcinoma is surgery, but many patients experience recurrence. The objective of the current study was to determine if adjuvant atezolizumab (vs placebo) delayed recurrence in patients with an increased risk of recurrence after resection.

Methods

IMmotion010 is a randomised, double-blind, multicentre, phase 3 trial conducted in 215 centres in 28 countries. Eligible patients were patients aged 18 years or older with renal cell carcinoma with a clear cell or sarcomatoid component and increased risk of recurrence. After nephrectomy with or without metastasectomy, patients were randomly assigned (1:1) to receive atezolizumab (1200 mg) or placebo (both intravenous) once every 3 weeks for 16 cycles or 1 year. Randomisation was done with an interactive voice-web response system. Stratification factors were disease stage (T2 or T3a vs T3b–c or T4 or N+ vs M1 no evidence of disease), geographical region (north America [excluding Mexico] vs rest of the world), and PD-L1 status on tumour-infiltrating immune cells (<1% vs ≥1% expression). The primary endpoint was investigator-assessed disease-free survival in the intention-to-treat population, defined as all patients who were randomised, regardless of whether study treatment was received. The safety-evaluable population included all patients randomly assigned to treatment who received any amount of study drug (ie, atezolizumab or placebo), regardless of whether a full or partial dose was received. This trial is registered with ClinicalTrials.gov, NCT03024996, and is closed to further accrual.

Findings

Between Jan 3, 2017, and Feb 15, 2019, 778 patients were enrolled; 390 (50%) were assigned to the atezolizumab group and 388 (50%) to the placebo group. At data cutoff (May 3, 2022), the median follow-up duration was 44·7 months (IQR 39·1–51·0). Median investigator-assessed disease-free survival was 57·2 months (95% CI 44·6 to not evaluable) with atezolizumab and 49·5 months (47·4 to not evaluable) with placebo (hazard ratio 0·93, 95% CI 0·75–1·15, p=0·50). The most common grade 3–4 adverse events were hypertension (seven [2%] patients who received atezolizumab vs 15 [4%] patients who received placebo), hyperglycaemia (ten [3%] vs six [2%]), and diarrhoea (two [1%] vs seven [2%]). 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo had a serious adverse event. There were no treatment-related deaths.

Interpretation

Atezolizumab as adjuvant therapy after resection for patients with renal cell carcinoma with increased risk of recurrence showed no evidence of improved clinical outcomes versus placebo. These study results do not support adjuvant atezolizumab for treatment of renal cell carcinoma.

Funding

F Hoffmann-La Roche and Genentech, a member of the Roche group.

中文翻译：

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辅助 atezolizumab 与安慰剂治疗切除后复发风险增加的肾细胞癌患者 (IMmotion010)：一项多中心、随机、双盲 3 期试验

背景

局部肾细胞癌的标准治疗是手术，但许多患者会出现复发。本研究的目的是确定辅助 atezolizumab（与安慰剂相比）是否可以延迟切除后复发风险增加的患者的复发。

方法

IMmotion010 是一项随机、双盲、多中心 3 期试验，在 28 个国家的 215 个中心进行。符合条件的患者是年龄 18 岁或以上、患有肾细胞癌、具有透明细胞或肉瘤样成分且复发风险增加的患者。肾切除术（伴或不伴转移灶切除术）后，患者被随机分配（1:1）接受atezolizumab（1200 mg）或安慰剂（均为静脉注射），每3周一次，持续16个周期或1年。随机化是通过交互式语音网络响应系统完成的。分层因素包括疾病分期（T2 或 T3a与T3b–c 或 T4 或 N+与M1 无疾病证据）、地理区域（北美 [不包括墨西哥]与世界其他地区）以及肿瘤浸润的 PD-L1 状态免疫细胞（<1% vs ≥1% 表达）。主要终点是研究者评估的意向治疗人群的无病生存期，意向治疗人群定义为随机分组的所有患者，无论是否接受研究治疗。可安全评估的人群包括随机分配接受任意剂量研究药物（即atezolizumab 或安慰剂）治疗的所有患者，无论接受的是全部剂量还是部分剂量。该试验已在 ClinicalTrials.gov 注册（NCT03024996），并已停止进一步累积。

发现

2017年1月3日至2019年2月15日期间，共有778名患者入组；390 名 (50%) 被分配到 atezolizumab 组，388 名 (50%) 被分配到安慰剂组。截至数据截止（2022 年 5 月 3 日），中位随访时间为 44·7 个月（IQR 39·1–51·0）。研究人员评估的阿替利珠单抗组无病生存期中位数为 57·2 个月（95% CI 44·6 至不可评估），安慰剂组为 49·5 个月（47·4 至不可评估）（风险比 0·93，95%） CI 0·75–1·15，p=0·50）。最常见的 3-4 级不良事件是高血压（接受 atezolizumab 治疗的患者为 7 名 [2%] ，接受安慰剂的患者为15 名 [4%]）、高血糖（接受阿特珠单抗治疗的患者为 7 名 [3%]，接受安慰剂的患者为6 名 [2%]）和腹泻（两个 [1%]与七个 [2%]）。69 名 (18%) 接受 atezolizumab 治疗的患者和 46 名 (12%) 接受安慰剂的患者出现严重不良事件。没有出现与治疗相关的死亡。

解释

Atezolizumab 作为复发风险增加的肾细胞癌患者切除后的辅助治疗，没有证据表明与安慰剂相比可以改善临床结果。这些研究结果不支持阿特珠单抗辅助治疗肾细胞癌。

资金

F Hoffmann-La Roche 和罗氏集团成员基因泰克。