小柯机器人

西班牙瓦尔德希布伦大学医院Enriqueta Felip团队研究了手术切除的IB–IIIA期非小细胞肺癌患者辅助化疗后接受辅助性阿特珠单抗治疗的效果。相关论文于2021年9月20日发表在《柳叶刀》杂志上。

目前需要新的辅助策略来改善早期非小细胞肺癌（NSCLC）患者完全手术切除后的预后。该研究旨在比较辅助铂类化疗后接受辅助性阿特珠单抗与最佳支持治疗的效果。

研究组在22个国家和地区的227个地点进行了一项随机、多中心、开放标签的3期临床研究。根据国际癌症联合会和美国癌症联合委员会的分期系统（第7版），符合条件的患者年龄为18岁或以上，完全切除IB期（肿瘤≥4cm）至IIIA期的 NSCLC。

将患者按1:1随机分配，分别在辅助性铂类化疗（1至4个周期）后接受辅助性阿特珠单抗或最佳支持治疗（观察和定期扫描疾病复发）。主要终点为研究人员评估的无病生存期，首先在II-IIIA期人群亚组（其肿瘤在1%或更多的肿瘤细胞上表达PD-L1 (SP263)）进行分层检测，然后是II-IIIA期所有患者，最后是意向治疗（ITT）人群（IB-IIIA期）。对所有分组患者进行安全性评估。

2015年10月7日至2018年9月19日，1280例患者在完全手术切除后入组。1269名患者接受了辅助化疗，1005名有资格随机分组，其中507名接受阿特珠单抗治疗，498名接受最佳支持治疗，最终每组有495人接受了治疗。在II-IIIA期人群中，经过32.2个月的中位随访后，对于肿瘤在1%或更多肿瘤细胞上表达PD-L1的患者而言，阿特珠单抗组的无病生存率显著优于最佳支持治疗组，风险比（HR）为0.66；对于II-IIIA期人群所有患者来说，阿特珠单抗组仍占优势，HR为0.79。在ITT人群中，无病生存的HR为0.81。495例患者中有53例（11%）发生阿特珠单抗相关的3级和4级不良事件，4例（1%）发生5级不良事件。

研究结果表明，与辅助化疗后的最佳支持治疗相比，阿特珠单抗对切除的II–IIIA期NSCLC患者的无病生存率有利，在肿瘤在1%或更多肿瘤细胞上表达PD-L1的亚组中明显有利，且无新的安全事件。

附：英文原文

Title: Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial

Author: Enriqueta Felip, Nasser Altorki, Caicun Zhou, Tibor Csszi, Ihor Vynnychenko, Oleksandr Goloborodko, Alexander Luft, Andrey Akopov, Alex Martinez-Marti, Hirotsugu Kenmotsu, Yuh-Min Chen, Antonio Chella, Shunichi Sugawara, David Voong, Fan Wu, Jing Yi, Yu Deng, Mark McCleland, Elizabeth Bennett, Barbara Gitlitz, Heather Wakelee

Issue&Volume: 2021-09-20

Abstract:

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.

DOI: 10.1016/S0140-6736(21)02098-5

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02098-5/fulltext

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