Atezolizumab Before and After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: A Phase II Nonrandomized Controlled Trial.

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology Jama Oncology Pub Date : 2024-09-01 DOI:10.1001/jamaoncol.2024.1897

Helen J Ross, David Kozono, Xiaofei F Wang, James John Urbanic, Terence M Williams, Garth D Nelson, David P Carbone, Dongjun Chung, Ryan Robb, Woo Yul Byun, Tiffany Talabere, Carter DuFrane, Ilze Bara, Katja Schulze, Michelle Brockman, Junheng Gao, Everett E Vokes, Thomas E Stinchcombe

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Abstract

Importance: Outcomes for patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiation therapy (CRT) have improved with adjuvant immune checkpoint inhibitors, with a reported 5-year overall survival benefit of approximately 10% for adjuvant durvalumab vs placebo after completion of CRT without progression and with preserved performance status. Starting atezolizumab prior to CRT may allow more patients to benefit from immunotherapy.

Objective: To evaluate clinical outcomes of patients treated with atezolizumab before and after CRT for unresectable stage III NSCLC.

Design, setting, and participants: This single-cohort, phase II, nonrandomized controlled trial was conducted at 11 US sites. Patients with pathologically confirmed, unresectable stage III NSCLC who were treatment naive and had good performance status were enrolled between January 3, 2018, and July 24, 2019. Data were locked on March 21, 2023.

Interventions: Patients received four 21-day cycles of atezolizumab, 1200 mg intravenously, with therapy administered on day 1 of each cycle. Patients not experiencing tumor progression continued to CRT (60 Gy to involved fields) concurrent with weekly carboplatin area under the curve of 2 and paclitaxel, 50 mg/m2, followed by planned consolidation carboplatin area under the curve of 6 and paclitaxel, 200 mg/m2, for two 21-day cycles. Patients not experiencing progression continued atezolizumab, 1200 mg, every 21 days to complete 1 year of therapy.

Main outcomes and measures: The primary end point was the disease control rate at 12 weeks. Secondary end points were progression-free survival, overall survival, overall response rate, safety, and translational science end points.

Results: A total of 62 patients (median [range] age, 63.9 [38.1-86.5] years; 32 female [51.6%]) were enrolled and received at least 1 dose of atezolizumab. The disease control rate at 12 weeks was 74.2% (80% CI, 65.7%-81.4%). Median progression-free survival was 30.0 months (95% CI, 15.8 to not evaluable), and the median overall survival was not reached. The overall survival rate at 24 months was 73.7% (95% CI, 63.4%-85.7%), and the overall response rate was 66.2%. Seventeen patients (27.4%) experienced grade 3 or higher immune-related adverse events, including 1 with grade 5 pneumonitis and 1 with grade 4 Guillain-Barré syndrome. Thirty patients (48.4%) experienced grade 3 or higher treatment-related adverse events.

Conclusions and relevance: These findings suggest that neoadjuvant atezolizumab merits further study based on safety and encouraging outcomes.

Trial registration: ClinicalTrials.gov Identifier: NCT03102242.

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化疗前后使用阿替珠单抗治疗不可切除的 III 期非小细胞肺癌：一项 II 期非随机对照试验。

重要性：接受化学放疗（CRT）治疗的不可切除的III期非小细胞肺癌（NSCLC）患者的预后在辅助免疫检查点抑制剂的治疗后有所改善，据报道，在完成CRT治疗后无进展且表现状态保持良好的情况下，辅助durvalumab与安慰剂相比的5年总生存率获益约为10%。在CRT之前开始使用atezolizumab可能会让更多患者从免疫疗法中获益：评估不可切除的III期NSCLC患者在CRT前后接受阿特珠单抗治疗的临床疗效：这项单队列、II期、非随机对照试验在美国11个地点进行。病理确诊为不可切除的 III 期 NSCLC 患者在 2018 年 1 月 3 日至 2019 年 7 月 24 日期间入组，这些患者均为治疗天真且表现良好。数据于2023年3月21日锁定：患者接受4个21天周期的atezolizumab治疗，静脉注射1200毫克，每个周期的第1天进行治疗。未出现肿瘤进展的患者继续接受 CRT 治疗（受累区域 60 Gy），同时每周接受卡铂曲线下面积为 2 和紫杉醇 50 mg/m2 的治疗，然后按计划接受卡铂曲线下面积为 6 和紫杉醇 200 mg/m2 的巩固治疗，共两个 21 天周期。未出现进展的患者继续使用阿特珠单抗（1200 毫克，每 21 天一次），以完成 1 年的治疗：主要终点是12周时的疾病控制率。次要终点为无进展生存期、总生存期、总反应率、安全性和转化科学终点：共有62名患者（中位数[范围]年龄为63.9[38.1-86.5]岁；32名女性[51.6%]）入组并接受了至少一次阿特珠单抗治疗。12周时的疾病控制率为74.2%（80% CI，65.7%-81.4%）。无进展生存期中位数为30.0个月（95% CI，15.8个月至无法评估），总生存期中位数未达到。24个月的总生存率为73.7%（95% CI，63.4%-85.7%），总反应率为66.2%。17名患者（27.4%）出现了3级或更高的免疫相关不良事件，其中1人出现5级肺炎，1人出现4级格林-巴利综合征。30名患者（48.4%）出现了3级或3级以上的治疗相关不良事件：这些研究结果表明，基于安全性和令人鼓舞的结果，新辅助阿特珠单抗值得进一步研究：试验注册：ClinicalTrials.gov Identifier：试验注册：ClinicalTrials.gov Identifier：NCT03102242。

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来源期刊

Jama Oncology Medicine-Oncology

CiteScore

37.50

自引率

1.80%

发文量

423

期刊介绍： At JAMA Oncology, our primary goal is to contribute to the advancement of oncology research and enhance patient care. As a leading journal in the field, we strive to publish influential original research, opinions, and reviews that push the boundaries of oncology science. Our mission is to serve as the definitive resource for scientists, clinicians, and trainees in oncology globally. Through our innovative and timely scientific and educational content, we aim to provide a comprehensive understanding of cancer pathogenesis and the latest treatment advancements to our readers. We are dedicated to effectively disseminating the findings of significant clinical research, major scientific breakthroughs, actionable discoveries, and state-of-the-art treatment pathways to the oncology community. Our ultimate objective is to facilitate the translation of new knowledge into tangible clinical benefits for individuals living with and surviving cancer.

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