对于转移性非小细胞肺癌 (NSCLC)，在免疫检查点抑制剂 (ICI) 治疗的基础上添加放射治疗 (RT) 可以产生协同抗癌作用，并治疗最具威胁性的肿瘤。我们假设在 ICI 基础上加入大剂量 RT 可以延长无进展生存期 (PFS)。在这项单臂 2 期试验中，45 名接受过抗 PD-1/抗 PD-L 治疗的转移性 NSCLC 患者2017年7月至2021年5月期间入组-1次ICI，为期4周。患者接受对1-4个颅外肿瘤的高剂量RT治疗，并继续ICI直至进展或出现不可接受的毒性。主要终点是 24 周时的 PFS，而历史对照率为 35%。 在 44 名可评估患者中，中位年龄为 71 岁，其中 75% 患有腺癌，64% 患有多转移性疾病，85% 的癌症具有已知的 PD-L1 PD-L1 阳性的百分比。治疗肿瘤的中位数为两个，最常见的剂量为 40 Gy，分 10 次（41/81 个肿瘤）。中位随访时间为 23.3 个月。该试验达到了主要结果：24 周 PFS 为 60%（95% CI 44-75%），高于历史对照率（p<0.001）。中位 PFS 为 6.9 个月（95% CI 4.0-13.5 个月），中位 OS 为 27.4 个月（95% CI 20.4 - 未达到）。几位在 ICI 治疗研究前疾病进展的患者对研究治疗取得了长达 53 个月的持久反应。局部复发率低：一年、二年、三年累计发生率为5%。观察到两种剂量限制性毒性 (5%)，包括一种 5 级肺炎。与单独接受 ICI 的历史对照相比，该策略改善了 24 周 PFS。出色的局部控制支持高剂量放疗在解决宏观疾病方面的功效。版权所有 © 2024。由 Elsevier Inc. 出版。

For metastatic non-small cell lung cancer (NSCLC), the addition of radiotherapy (RT) to immune checkpoint inhibitor (ICI) therapy could have synergistic anti-cancer effects and address the most threatening tumors. We posited that the addition of high-dose RT to ICI could prolong progression-free survival (PFS).In this single arm phase 2 trial, 45 patients with metastatic NSCLC who had received an anti-PD-1/anti-PD-L-1 ICI for 4+ weeks were enrolled from July 2017-May 2021. Patients received high-dose RT to 1-4 extracranial tumors and continued ICI until progression or unacceptable toxicity. The primary endpoint was PFS at 24 weeks, comparing to a historical control rate of 35%.Of 44 evaluable patients, median age was 71, 75% had adenocarcinoma, 64% had polymetastatic disease, and 85% of cancers with known PD-L1 percentage were PD-L1 positive. Median number of treated tumors was two and most common dose was 40 Gy in 10 fractions (41/81 tumors). Median follow-up was 23.3 months. The trial met the primary outcome: 24-week PFS was 60% (95% CI 44-75%), higher than the historical control rate (p<0.001). Median PFS was 6.9 months (95% CI 4.0-13.5 mo) and median OS was 27.4 months (95% CI 20.4-not reached). Several patients with pre-study disease progression on ICI treatment achieved durable responses to study treatment, up to 53 months. Local recurrence rate was low: cumulative incidence of 5% at one, two, and three years. Two dose-limiting toxicities were observed (5%), including one grade 5 pneumonitis.The strategy improved 24-week PFS compared to historical controls receiving ICI alone. The excellent local control supports the efficacy of high-dose RT in addressing macroscopic disease.Copyright © 2024. Published by Elsevier Inc.