Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
NewYork-Presbyterian Hospital, Weill Cornell Medicine, New York, USA.
Ann Oncol. 2023 Oct;34(10):907-919. doi: 10.1016/j.annonc.2023.07.001. Epub 2023 Jul 17.
IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in the programmed death-ligand 1 (PD-L1)-positive and all stage II-IIIA non-small-cell lung cancer (NSCLC) populations, at the DFS interim analysis. Results of the first interim analysis of overall survival (OS) are reported here.
The design, participants, and primary-endpoint DFS outcomes have been reported for this phase III, open-label, 1 : 1 randomised study of atezolizumab (1200 mg q3w; 16 cycles) versus BSC after adjuvant platinum-based chemotherapy (1-4 cycles) in adults with completely resected stage IB (≥4 cm)-IIIA NSCLC (per the Union Internationale Contre le Cancer and American Joint Committee on Cancer staging system, 7th edition). Key secondary endpoints included OS in the stage IB-IIIA intent-to-treat (ITT) population and safety in randomised treated patients. The first pre-specified interim analysis of OS was conducted after 251 deaths in the ITT population. Exploratory analyses included OS by baseline PD-L1 expression level (SP263 assay).
At a median of 45.3 months' follow-up on 18 April 2022, 127 of 507 patients (25%) in the atezolizumab arm and 124 of 498 (24.9%) in the BSC arm had died. The median OS in the ITT population was not estimable; the stratified hazard ratio (HR) was 0.995 [95% confidence interval (CI) 0.78-1.28]. The stratified OS HRs (95% CI) were 0.95 (0.74-1.24) in the stage II-IIIA (n = 882), 0.71 (0.49-1.03) in the stage II-IIIA PD-L1 tumour cell (TC) ≥1% (n = 476), and 0.43 (95% CI 0.24-0.78) in the stage II-IIIA PD-L1 TC ≥50% (n = 229) populations. Atezolizumab-related adverse event incidences remained unchanged since the previous analysis [grade 3/4 in 53 (10.7%) and grade 5 in 4 (0.8%) of 495 patients, respectively].
Although OS remains immature for the ITT population, these data indicate a positive trend favouring atezolizumab in PD-L1 subgroup analyses, primarily driven by the PD-L1 TC ≥50% stage II-IIIA subgroup. No new safety signals were observed after 13 months' additional follow-up. Together, these findings support the positive benefit-risk profile of adjuvant atezolizumab in this setting.
IMpower010（NCT02486718）在程序性死亡配体 1（PD-L1）阳性和所有 II-IIIA 期非小细胞肺癌（NSCLC）人群中，与最佳支持治疗（BSC）相比，在铂类化疗后，接受辅助阿替利珠单抗显著改善了无病生存期（DFS），这是在 DFS 中期分析中得出的结果。现将首次总生存期（OS）的中期分析结果报告如下。
这项 III 期、开放标签、1:1 随机研究对接受完全切除的 IB 期（≥4cm）-IIIA NSCLC（国际抗癌联盟和美国癌症联合委员会第 7 版分期系统）的成人进行了评估，患者在铂类化疗后接受辅助阿替利珠单抗（1200mg，q3w；16 个周期）或 BSC。该研究的设计、参与者和主要终点 DFS 结果已经报告过。次要终点包括 IIB-IIIA 期 ITT 人群的 OS 和随机治疗患者的安全性。在 ITT 人群中，在 251 例死亡后进行了首次预定的 OS 中期分析。探索性分析包括基于基线 PD-L1 表达水平（SP263 检测）的 OS。
截至 2022 年 4 月 18 日，45.3 个月的中位随访时，阿替利珠单抗组的 507 例患者中有 127 例（25%）和 BSC 组的 498 例患者中有 124 例（24.9%）死亡。ITT 人群的中位 OS 不可估计；分层风险比（HR）为 0.995[95%置信区间（CI）0.78-1.28]。分层 OS HR（95%CI）在 IIB-IIIA 期（n=882）为 0.95（0.74-1.24），在 IIB-IIIA 期 PD-L1 肿瘤细胞（TC）≥1%（n=476）为 0.71（0.49-1.03），在 IIB-IIIA 期 PD-L1 TC≥50%（n=229）为 0.43（95%CI 0.24-0.78）。自上次分析以来，阿替利珠单抗相关不良事件的发生率保持不变[495 例患者中分别有 53 例（10.7%）为 3/4 级和 4 例（0.8%）为 5 级]。
尽管 ITT 人群的 OS 仍不成熟，但这些数据表明，在 PD-L1 亚组分析中，阿替利珠单抗具有阳性趋势，主要是由 PD-L1 TC≥50%的 IIB-IIIA 亚组驱动。在额外 13 个月的随访后，未观察到新的安全性信号。这些发现共同支持了辅助阿替利珠单抗在这一情况下的积极获益风险特征。
