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.

Funding

F Hoffmann-La Roche and Genentech.

中文翻译：

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在切除的 IB-IIIA 期非小细胞肺癌 (IMpower010) 中辅助化疗后辅助atezolizumab：一项随机、多中心、开放标签、3 期试验

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。我们旨在评估这些患者在铂类辅助化疗后辅助阿特珠单抗与最佳支持治疗。

方法

IMpower010 是一项在 22 个国家和地区的 227 个地点进行的随机、多中心、开放标签、3 期研究。根据国际抗癌联盟和美国癌症联合委员会分期系统（第 7 版），符合条件的患者为 18 岁或以上，完全切除的 IB 期（肿瘤≥4 cm）至 IIIA 期 NSCLC。患者被随机分配（1:1）通过置换块法（块大小为 4）接受辅助阿特珠单抗（每 21 天 1200 毫克；持续 16 个周期或 1 年）或最佳支持治疗（观察和定期扫描疾病铂类辅助化疗（一到四个周期）后复发）。主要终点，研究者评估的无病生存期，首先在 II-IIIA 期人群亚组中进行分层测试，其肿瘤在 1% 或更多的肿瘤细胞 (SP263) 上表达 PD-L1，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）。在随机分配并接受阿特珠单抗或最佳支持治疗的所有患者中评估了安全性。IMpower010 在 ClinicalTrials.gov 注册，NCT02486718（活跃，不招募）。

发现

2015 年 10 月 7 日至 2018 年 9 月 19 日期间，1280 名患者在完全切除后入组。1269 名患者接受了辅助化疗，其中 1005 名患者符合随机分组到阿特珠单抗 (n=507) 或最佳支持治疗 (n=498) 的条件；每组495人接受治疗。在 II-IIIA 期人群中位随访 32·2 个月（IQR 27·4-38·3）后，与 II-IIIA 期人群的最佳支持治疗相比，atezolizumab 治疗提高了无病生存率其肿瘤在 1% 或更多的肿瘤细胞上表达 PD-L1（HR 0·66；95% CI 0·50–0·88；p=0·0039）和 II-IIIA 期人群中的所有患者（0 ·79；0·64–0·96；p=0·020)。在 ITT 人群中，无病生存的 HR 为 0·81（0·67–0·99；p=0·040）。

解释

IMpower010 显示，在切除的 II-IIIA 期 NSCLC 患者中，与辅助化疗后最佳支持治疗相比，使用 atezolizumab 可带来无病生存获益，在肿瘤细胞表达 PD-L1 1% 或更多的亚组中显着获益，并且没有新的安全信号。辅助化疗后的 Atezolizumab 为切除的早期 NSCLC 患者提供了一种有希望的治疗选择。

资金

F Hoffmann-La Roche 和基因泰克。