ImportanceOutcomes 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.ObjectiveTo evaluate clinical outcomes of patients treated with atezolizumab before and after CRT for unresectable stage III NSCLC.Design, Setting, and ParticipantsThis 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.InterventionsPatients 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 MeasuresThe 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.ResultsA 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 RelevanceThese findings suggest that neoadjuvant atezolizumab merits further study based on safety and encouraging outcomes.Trial RegistrationClinicalTrials.gov Identifier: NCT03102242

中文翻译：

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Atezolizumab 在不可切除的 III 期非小细胞肺癌放化疗前后


重要性接受放化疗 （CRT） 治疗的不可切除的 III 期非小细胞肺癌 （NSCLC） 患者的结局在辅助免疫检查点抑制剂治疗后得到改善，据报道，在完成 CRT 后，辅助 durvalumab 与安慰剂相比，辅助 durvalumab 的 5 年总生存率约为 10%，无进展且体能状态保持不变。在 CRT 之前开始 atezolizumab 可能会让更多患者从免疫治疗中受益。目的评估 CRT 前后接受 atezolizumab 治疗不可切除的 III 期患者的临床结局 NSCLC.Design、环境和参与者这项单队列、II 期、非随机对照试验在美国 11 个地点进行。2018 年 1 月 3 日至 2019 年 7 月 24 日期间，纳入了经病理证实、不可切除的 III 期 NSCLC 患者，这些患者未接受过治疗且体能状态良好。数据于 2023 年 3 月 21 日锁定。干预患者接受四个 21 天周期的 atezolizumab，1200 mg 静脉注射，在每个周期的第 1 天进行治疗。未出现肿瘤进展的患者继续进行 CRT （60 Gy 至受累区域），同时每周卡铂曲线下面积 2 和紫杉醇 50 mg/m2，然后计划巩固卡铂曲线下面积 6 和紫杉醇 200 mg/m2，两个 21 天的周期。未出现进展的患者继续每 21 天服用 1200 毫克阿替利珠单抗以完成 1 年的治疗。主要结局和测量主要终点是 12 周时的疾病控制率。次要终点是无进展生存期、总生存期、总缓解率、安全性和转化科学终点。结果共有 62 例患者 （中位 [范围] 年龄，63.9 [38.1-86.5] 年;32 名女性 [51.6%]） 入组并接受了至少 1 剂 atezolizumab。12 周时的疾病控制率为 74.2% （80% CI，65.7%-81.4%）。中位无进展生存期为 30.0 个月 （95% CI，15.8 至无法评估），未达到中位总生存期。24 个月的总生存率为 73.7% （95% CI，63.4%-85.7%），总缓解率为 66.2%。17 例患者 （27.4%） 经历了 3 级或更高级别的免疫相关不良事件，包括 1 例 5 级肺炎和 1 例 4 级格林-巴利综合征。30 例患者 （48.4%） 经历了 3 级或更高级别的治疗相关不良事件。结论和相关性这些发现表明，基于安全性和令人鼓舞的结果，新辅助 atezolizumab 值得进一步研究。试验注册临床试验。gov 标识符： NCT03102242