一线阿替利珠单抗治疗与单药化疗治疗不符合含铂治疗的非小细胞肺癌患者（IPSOS）：3期研究

SCI

18 July 2023

First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study

(The Lancet, IF: 168.9)

Siow Ming Lee, Christian Schulz, Kumar Prabhash, Dariusz Kowalski, Aleksandra Szczesna, Baohui Han, Achim Rittmeyer, Toby Talbot, David Vicente, Raffaele Califano, Diego Cortinovis, Anh Tuan Le, Dingzhi Huang, Geoffrey Liu, Federico Cappuzzo, Jessica Reyes Contreras, Martin Reck, Ramon Palmero, Milena Perez Mak, Youyou Hu, Stefanie Morris, Elen Höglander, Mary Connors, Alice M Biggane, Hans Kristian Vollan, Solange Peters

CORRESPONDENCE TO: sm.lee@nhs.net

Background  背景

Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy.

尽管晚期或转移性非小细胞肺癌（NSCLC）患者的免疫治疗取得了进步，但关键的一线试验仅限于东部肿瘤合作组织（ECOG PS）体能状态评分为0-1且中位年龄为65岁或更年轻的患者。我们旨在比较一线阿替利珠单抗单药治疗与单剂化疗在不符合铂类化疗条件的患者中的疗效和安全性。

Methods 方法

This trial was a phase 3, open-label, randomised controlled study conducted at 91 sites in 23 countries across Asia, Europe, North America, and South America. Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0–1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy. Patients were randomised 2:1 by permuted-block randomisation (block size of six) to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or gemcitabine [intravenous]; dosing per local label) at 3-weekly or 4-weekly cycles. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety analyses were conducted in the safety-evaluable population, which included all randomised patients who received any amount of atezolizumab or chemotherapy. This trial is registered with ClinicalTrials.gov, NCT03191786.

该试验是一项3期、开放标签、随机对照研究，在亚洲、欧洲、北美和南美23个国家的91个地点进行。符合条件的患者患有IIIB或IV期非小细胞肺癌并且研究者认为不适用含铂双药联合化疗，包括ECOG PS 评分2或3，或70岁或以上、ECOG PS 0–1、且患有大量合并症或含铂双药化疗禁忌症。患者以2:1的比例随机分组（分组大小为6），每3周静脉注射1200 mg 阿替利珠单抗，或在3周或4周周期接受单剂化疗（长春瑞滨[口服或静脉注射]或吉西他滨[静脉注射]；按局部标记给药）。主要终点是在意向治疗人群中评估的总生存率。在安全性可评估人群中进行了安全性分析，其中包括所有随机接受任何剂量阿替利珠单抗治疗或化疗的患者。该试验在ClinicalTrials.gov注册，NCT03191786。

Findings 结果

Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). Atezolizumab improved overall survival compared with chemotherapy (median overall survival 10·3 months [95% CI 9·4–11·9] vs 9·2 months [5·9–11·2]; stratified hazard ratio 0·78 [0·63–0·97], p=0·028), with a 2-year survival rate of 24% (95% CI 19·3–29·4) with atezolizumab compared with 12% (6·7–18·0) with chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilisation or improvement of patient-reported health-related quality-of-life functioning scales and symptoms and fewer grade 3–4 treatment-related adverse events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three [1%] vs four [3%]).

在2017年9月11日至2019年9月23日期间，453名患者被纳入并随机接受阿替利珠单抗治疗（n=302）或化疗（n=151）。与化疗相比，阿替利珠单抗提高了总生存率（中位总生存期10.3个月[95%CI 9.4-11.9]vs 9.2个月[5.9-11.2]；分层危险比0.78[0.63-0.97]，p=0.028），阿替利珠单抗的2年生存率为24%（95%CI 19.3-29.4），而化疗为12%（6.7-18.0）。与化疗相比，阿替利珠单抗与患者报告的健康相关生活质量功能量表和症状的稳定或改善以及较少的3-4级治疗相关不良事件（300例中的49例[16%]对147例中的49[33%]）和治疗相关死亡（3例[1%]对4例[3%]）有关。

Interpretation 解释

First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy.

与单剂化疗相比，阿替利珠单抗单药一线治疗与总生存率提高、2年生存率翻倍、维持生活质量和良好的安全性有关。这些数据支持阿替利珠单抗单药治疗作为不符合铂类化疗条件的晚期非小细胞肺癌患者的潜在一线治疗选择。

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