Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer: Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials.
Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer: Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials.
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DOI：
10.1001/jamaoncol.2022.7711
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发表时间：
2023-04-01
期刊：
影响因子：
28.4
通讯作者：
West, Howard J.
中科院分区：
文献类型：
--
作者：
Socinski, Mark A.;Jotte, Robert M.;Cappuzzo, Federico;Nishio, Makoto;Mok, Tony S. K.;Reck, Martin;Finley, Gene G.;Kaul, Monika D.;Yu, Wei;Paranthaman, Nindhana;Bara, Ilze;West, Howard J.
对3项随机临床试验的汇总数据进行分析，评估免疫相关不良事件与atezolizumab在晚期非小细胞肺癌患者中疗效之间的相关性。免疫相关不良事件（irAE）与atezolizumab治疗晚期非鳞状非小细胞肺癌（NSCLC）疗效之间的关系是什么？对纳入2503例NSCLC患者的3项atezolizumab-化学免疫治疗联合治疗的汇总III期随机临床试验进行的事后分析显示，一般而言，在含atezolizumab组和对照组中，发生低级别irAE的患者的总生存期长于未发生irAE的患者。atezolizumab联合治疗的1 - 2级irAE通常与总生存期改善相关，而3 - 5级irAE则与总生存期改善相关。这些结果表明，低级别irAE与生存期改善相关，尤其是atezolizumab，进一步支持含atezolizumab的一线治疗方案用于晚期NSCLC。免疫检查点抑制剂（ICI）癌症治疗引起的免疫相关不良事件（irAE）可能预示着改善的结局。使用3项III期ICI研究的汇总数据，评价晚期非小细胞肺癌（NSCLC）患者中irAE与atezolizumab疗效之间的相关性。IMpower 130、IMpower 132和IMpower 150是III期、多中心、开放标签、随机化临床试验，旨在评价atezolizumab联合化疗免疫治疗的疗效和安全性。参与者是未经化疗的IV期非鳞状NSCLC成人。这些事后分析于2022年2月进行。符合条件的患者按2：1的比例随机分配接受atezolizumab+卡铂+nab-紫杉醇或单独化疗（IMpower 130）;按1：1的比例接受atezolizumab+卡铂或顺铂+培美曲塞或单独化疗（IMpower 132）;按1：1：1的比例接受atezolizumab+贝伐珠单抗+卡铂和紫杉醇、atezolizumab+卡铂和紫杉醇或贝伐珠单抗+卡铂和紫杉醇（IMpower 150）。按治疗（含atezolizumab vs对照）、irAE状态（有vs无）和最高irAE级别（1-2 vs 3-5）分析了IMpower 130（截止日期：2018年3月15日）、IMpower 132（截止日期：2018年5月22日）和IMpower 150（截止日期：2019年9月13日）的汇总数据。为了解释永久偏倚，使用时间依赖性考克斯模型和自基线起1、3、6和12个月时irAE发生率的里程碑分析来估计总生存期（OS）的风险比（HR）。在2503例随机化患者中，1577例在含atezolizumab组，926例在对照组。患者的平均（SD）年龄为63.1（9.4）岁和63.0岁（9.3）年，950（百分之六十点二）及五百六十九atezolizumab组和对照组分别有61.4%（61.4%）为男性。（atezolizumab，n = 753;对照，n = 289）和无（atezolizumab，n = 824;对照，n = 637）。atezolizumab组中，发生1 - 2级irAE和3 - 5级irAE患者的OS HR（95% CI）1、3、6和12个月亚组中（各vs未发生irAE的患者）的发生率分别为0.78 0.74（0.63-0.87）和1.23（0.93-1.64）; 0.77（0.65-0.90）和1.1（0.81-1.42）; 0.72（0.59-0.89）和0.87（0.61-1.25）。在这项对3项随机临床试验的汇总分析中，在两组和各标志点中，观察到发生轻度至中度irAE的患者的OS长于未发生轻度至中度irAE的患者。这些结果进一步支持使用含atezolizumab的一线方案治疗晚期非鳞状NSCLC。ClinicalTrials.gov标识符：NCT 02367781、NCT 02657434和NCT 02366143
This analysis of pooled data from 3 randomized clinical trials evaluates the association between immune-related adverse events and atezolizumab efficacy in patients with advanced non–small cell lung cancer. What is the association between immune-related adverse events (irAEs) and atezolizumab efficacy in advanced nonsquamous non–small cell lung cancer (NSCLC)? Post hoc analyses of 3 pooled phase 3 randomized clinical trials of atezolizumab-chemoimmunotherapy combinations including 2503 patients with NSCLC showed that generally, overall survival was longer in patients with low-grade irAEs than without in the atezolizumab-containing and control arms. Grade 1 to 2 irAEs with atezolizumab combinations were generally associated with improved overall survival vs grade 3 to 5 irAEs. These findings suggested an association between low-grade irAEs and improved survival, particularly with atezolizumab, further supporting the use of first-line atezolizumab-containing regimens for advanced NSCLC. Immune-related adverse events (irAEs) arising from immune checkpoint inhibitor (ICI) cancer therapy may potentially predict improved outcomes. To evaluate the association between irAEs and atezolizumab efficacy in patients with advanced non–small cell lung cancer (NSCLC) using pooled data from 3 phase 3 ICI studies. IMpower130, IMpower132, and IMpower150 were phase 3, multicenter, open-label, randomized clinical trials to evaluate the efficacy and safety of chemoimmunotherapy combinations involving atezolizumab. Participants were chemotherapy-naive adults with stage IV nonsquamous NSCLC. These post hoc analyses were conducted during February 2022. Eligible patients were randomly assigned 2:1 to receive atezolizumab with carboplatin plus nab-paclitaxel, or chemotherapy alone (IMpower130); 1:1 to receive atezolizumab with carboplatin or cisplatin plus pemetrexed, or chemotherapy alone (IMpower132); and 1:1:1 to receive atezolizumab plus bevacizumab plus carboplatin and paclitaxel, atezolizumab plus carboplatin and paclitaxel, or bevacizumab plus carboplatin and paclitaxel (IMpower150). Pooled data from IMpower130 (cutoff: March 15, 2018), IMpower132 (cutoff: May 22, 2018), and IMpower150 (cutoff: September 13, 2019) were analyzed by treatment (atezolizumab-containing vs control), irAE status (with vs without), and highest irAE grade (1-2 vs 3-5). To account for immortal bias, a time-dependent Cox model and landmark analyses of irAE occurrence at 1, 3, 6, and 12 months from baseline were used to estimate the hazard ratio (HR) of overall survival (OS). Of 2503 randomized patients, 1577 were in the atezolizumab-containing arm and 926 were in the control arm. The mean (SD) age of patients was 63.1 (9.4) years and 63.0 (9.3) years, and 950 (60.2%) and 569 (61.4%) were male, respectively, in the atezolizumab arm and the control arm. Baseline characteristics were generally balanced between patients with irAEs (atezolizumab, n = 753; control, n = 289) and without (atezolizumab, n = 824; control, n = 637). In the atezolizumab arm, OS HRs (95% CI) in patients with grade 1 to 2 irAEs and grade 3 to 5 irAEs (each vs those without irAEs) in the 1-, 3-, 6-, and 12-month subgroups were 0.78 (0.65-0.94) and 1.25 (0.90-1.72), 0.74 (0.63-0.87) and 1.23 (0.93-1.64), 0.77 (0.65-0.90) and 1.1 (0.81-1.42), and 0.72 (0.59-0.89) and 0.87 (0.61-1.25), respectively. In this pooled analysis of 3 randomized clinical trials, longer OS was observed in patients with vs without mild to moderate irAEs in both arms and across landmarks. These findings further support the use of first-line atezolizumab-containing regimens for advanced nonsquamous NSCLC. ClinicalTrials.gov Identifiers: NCT02367781, NCT02657434, and NCT02366143
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