美国希望之城综合癌症中心Sumanta Kumar Pal团队比较了阿特珠单抗与安慰剂辅助治疗对肾细胞癌切除术后复发风险增加患者的影响。相关论文于2022年9月10日发表在《柳叶刀》杂志上。

局部肾细胞癌的治疗标准是手术，但许多患者会经历复发。该研究旨在确定辅助性阿特珠单抗（与安慰剂相比）是否延迟了切除术后复发风险较大患者的复发。

研究组进行了一项随机、双盲、多中心、3期临床试验，在28个国家的215个中心进行。招募18岁及以上、具有透明细胞或肉瘤样成分、复发风险增加的肾细胞癌患者。在接受肾切除术伴或不伴转移切除术后，将患者按1：1随机分配，分别接受阿特珠单抗（1200 mg）或安慰剂（均静脉注射）治疗，每3周一次，共16个周期或1年。使用交互式语音网络响应系统进行随机分组。

分层因素包括疾病分期（T2或T3a vs T3b–c或T4或N+ vs M1无疾病证据）、地理区域（北美[不包括墨西哥] vs 世界其他地区）和肿瘤浸润免疫细胞的PD-L1状态（<1% vs ≥1%表达）。主要终点是研究者评估意向治疗人群的无病生存率，定义为随机分组的所有患者，无论是否接受研究治疗。安全性可评估人群包括所有随机分配接受任何剂量研究药物（即阿特珠单抗或安慰剂）治疗的患者，无论是否接受全部或部分剂量。

2017年1月3日至2019年2月15日，共778名患者入选；390（50%）被分配到阿特珠单抗组，388（50%）被分配到安慰剂组。在数据截止日（2022年5月3日），中位随访时间为44.7个月。阿特珠单抗组中研究者评估的中位无病生存期为57.2个月，安慰剂组为49.5个月，风险比为0.93。

最常见的3-4级不良事件是高血压（阿特珠单抗组中有7例[2%]患者，安慰剂组有15例[4%]）、高血糖（两组分别有10例[3%]与6例[2%]），以及腹泻（分别有2例[1%]与7例[3%]）。阿特珠单抗组中有69名（18%）患者出现严重不良事件，安慰剂组有46名（12%）。无治疗相关死亡。

研究结果表明，与安慰剂相比，阿特珠单抗作为肾细胞癌术后复发风险增加患者的辅助治疗没有证据表明可改善临床结局。

附：英文原文

Title: Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomised, double-blind, phase 3 trial

Author: Sumanta Kumar Pal, Robert Uzzo, Jose Antonio Karam, Viraj A Master, Frede Donskov, Cristina Suarez, Laurence Albiges, Brian Rini, Yoshihiko Tomita, Ariel Galapo Kann, Giuseppe Procopio, Francesco Massari, Matthew Zibelman, Igor Antonyan, Mahrukh Huseni, Debasmita Basu, Bo Ci, William Leung, Omara Khan, Sarita Dubey, Axel Bex

Issue&Volume: 2022-09-10

Abstract:

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.

DOI: 10.1016/S0140-6736(22)01658-0

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01658-0/fulltext