Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial
Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial
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DOI：
10.1016/s0140-6736(21)02098-5
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发表时间：
2021-10-07
期刊：
影响因子：
168.9
通讯作者：
Wakelee, Heather
中科院分区：
文献类型：
--
作者：
Felip, Enriqueta;Altorki, Nasser;Wakelee, Heather
背景 需要新的辅助策略来优化早期非小细胞肺癌（NSCLC）患者完全手术切除后的结果。我们的目的是评估这些患者在辅助铂类化疗后使用阿替利珠单抗与最佳支持治疗的比较。方法 IMpower010 是一项随机、多中心、开放标签的 3 期研究，在 22 个国家和地区的 227 个地点进行。符合条件的患者为 18 岁或以上，根据国际抗癌联盟和美国癌症联合委员会分期系统（第七版）完全切除的 IB 期（肿瘤 >= 4 cm）至 IIIA NSCLC。患者通过置换分区法（分区大小为 4）随机分配（1:1），接受辅助阿替利珠单抗（每 21 天 1200 mg；持续 16 个周期或 1 年）或在辅助铂类化疗（1 至 4 个周期）后接受最佳支持治疗（观察和定期扫描疾病复发）。主要终点，即研究者评估的无病生存率，首先在肿瘤细胞表达 PD-L1 1% 或以上的 II-IIIA 期人群亚组 (SP263) 中进行分层测试，然后是 II-IIIA 期人群中的所有患者，最后是意向治疗 (ITT) 人群（IB-IIIA 期）。对随机分配并接受 atezolizumab 或最佳支持治疗的所有患者进行安全性评估。 IMpower010已在ClinicalTrials.gov注册，NCT02486718（活跃，未招募）。调查结果2015年10月7日至2018年9月19日期间，1280名完全切除后的患者入组。 1269 名患者接受了辅助化疗，其中 1005 名患者有资格随机分配至 atezolizumab (n=507) 或最佳支持治疗组 (n=498)；每组 495 人接受治疗。在 II-IIIA 期人群中中位随访 32.2 个月（IQR 27.4-38.3）后，与最佳支持治疗相比，对于肿瘤在 1% 或更多肿瘤细胞上表达 PD-L1 的 II-IIIA 期人群患者（HR 0.66；95% CI 0.50-0.88；p=0.0039）以及II-IIIA 期人群（0.79；0.64-0.96；p=0.020）。在 ITT 人群中，无病生存 HR 为 0.81 (0.67-0.99；p=0.040)。 495 名患者中有 53 名 (11%) 发生了 Atezolizumab 相关的 3 级和 4 级不良事件，4 名患者 (1%) 发生了 5 级事件。 解释 IMpower010 显示，在切除的 II-IIIA 期 NSCLC 患者中，与辅助化疗后的最佳支持治疗相比，atezolizumab 具有无病生存获益，在肿瘤细胞表达 PD-L1 的亚组中获益显着，且无新的安全性信号。辅助化疗后的 Atezolizumab 为切除的早期 NSCLC 患者提供了一种有前景的治疗选择。版权所有 (C) 2021 爱思唯尔有限公司。保留所有权利。
Background Novel adjuvant strategies are needed to optimise outcomes after complete surgical resection in patients with early-stage non-small-cell lung cancer (NSCLC). We aimed to evaluate adjuvant atezolizumab versus best supportive care after adjuvant platinum-based chemotherapy in these patients.Methods IMpower010 was a randomised, multicentre, open-label, phase 3 study done at 227 sites in 22 countries and regions. Eligible patients were 18 years or older with completely resected stage IB (tumours >= 4 cm) to IIIA NSCLC per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system (7th edition). Patients were randomly assigned (1:1) by a permuted-block method (block size of four) to receive adjuvant atezolizumab (1200 mg every 21 days; for 16 cycles or 1 year) or best supportive care (observation and regular scans for disease recurrence) after adjuvant platinum-based chemotherapy (one to four cycles). The primary endpoint, investigator-assessed disease-free survival, was tested hierarchically first in the stage II-IIIA population subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells (SP263), then all patients in the stage II-IIIA population, and finally the intention-to-treat (ITT) population (stage IB-IIIA). Safety was evaluated in all patients who were randomly assigned and received atezolizumab or best supportive care. IMpower010 is registered with ClinicalTrials.gov, NCT02486718 (active, not recruiting).Findings Between Oct 7, 2015, and Sept 19, 2018, 1280 patients were enrolled after complete resection. 1269 received adjuvant chemotherapy, of whom 1005 patients were eligible for randomisation to atezolizumab (n=507) or best supportive care (n=498); 495 in each group received treatment. After a median follow-up of 32.2 months (IQR 27.4-38.3) in the stage II-IIIA population, atezolizumab treatment improved disease-free survival compared with best supportive care in patients in the stage II-IIIA population whose tumours expressed PD-L1 on 1% or more of tumour cells (HR 0.66; 95% CI 0.50-0.88; p=0.0039) and in all patients in the stage II-IIIA population (0.79; 0.64-0.96; p=0.020). In the ITT population, HR for disease-free survival was 0.81 (0.67-0.99; p=0.040). Atezolizumab-related grade 3 and 4 adverse events occurred in 53 (11%) of 495 patients and grade 5 events in four patients (1%).Interpretation IMpower010 showed a disease-free survival benefit with atezolizumab versus best supportive care after adjuvant chemotherapy in patients with resected stage II-IIIA NSCLC, with pronounced benefit in the subgroup whose tumours expressed PD-L1 on 1% or more of tumour cells, and no new safety signals. Atezolizumab after adjuvant chemotherapy offers a promising treatment option for patients with resected early-stage NSCLC. Copyright (C) 2021 Elsevier Ltd. All rights reserved.