巩固性 durvalumab 是一种抗程序性死亡配体 1 (PDL1) 免疫检查点抑制剂，在同步放化疗后给药可改善局部晚期非小细胞肺癌 (NSCLC) 患者的预后，而不会显着增加毒性。我们研究了胸部放疗 (RT) 的无化疗方案，并同时使用巩固性 durvalumab。 这项单臂 II 期试验纳入了 III 期 NSCLC（无论肿瘤 PDL1 表达如何）、体能状态 ECOG 0-1、肺功能充足的患者，以及满足标准器官限制的 RT 场。参与者接受两个周期的 durvalumab（每 4 周 1500 mg）同时接受胸部放疗（60 Gy，分 30 次），随后接受最多 13 个周期的巩固 durvalumab。在 10 名患者入组后，该试验因临床结果不佳而关闭。中位随访时间为 12 个月，其中 5 名患者出现疾病进展，8 名患者死亡。 6 名患者经历了 15 起与治疗相关的 3 级以上事件，其中包括 1 起巩固期间的 4 级急性肾损伤和 2 起致命的肺部事件。一名主动吸烟者在同时阶段发生了一起致命的肺部事件；另一个发生在第一个巩固性 durvalumab 周期之后。 12 个月时无进展生存 (PFS) 的主要终点为 20%（PDL1≥1% 为 50%，PDL1 不可用或 <1% 为 0%）。对于 PDL1 ≥1%、<1% 和不可用，中位总生存期 (OS) 未达到，分别为 10.5 个月和 7 个月。在 PDL1 未选择的 III 期 NSCLC 中，胸部放疗加同步和巩固性 durvalumab 与高- 级毒性和早期疾病进展。版权所有 © 2024。由 Elsevier Inc. 出版。

Consolidative durvalumab, an anti-programmed death ligand 1 (PDL1) immune checkpoint inhibitor, administered after concurrent chemoradiation improves outcomes of patients with locally advanced non-small cell lung cancer (NSCLC) without substantially increasing toxicities. We studied a chemotherapy-free regimen of thoracic radiotherapy (RT) with concurrent and consolidative durvalumab.This single-arm phase II trial enrolled patients with stage III NSCLC (regardless of tumor PDL1 expression), performance status ECOG 0-1, adequate pulmonary function, and RT fields meeting standard organ constraints. Participants received two cycles of durvalumab (1500 mg every 4 weeks) concurrently with thoracic RT (60 Gy in 30 fractions), followed by up to 13 cycles of consolidative durvalumab.After 10 patients were enrolled, the trial was closed due to poor clinical outcomes. With a median follow-up of 12 months, five patients had disease progression and eight patients died. Six patients experienced 15 treatment-related, grade ≥3 events, including one grade 4 acute kidney injury during consolidation and two fatal pulmonary events. One fatal pulmonary event occurred during the concurrent phase in an active smoker; the other occurred after the first cycle of consolidative durvalumab. The primary endpoint of progression-free survival (PFS) at 12 months was 20% (50% for PDL1≥1% versus 0% for PDL1 unavailable or <1%). Median overall survival (OS) was not reached, 10.5 months, and 7 months, for PDL1 ≥1%, <1%, and unavailable, respectively.In PDL1 unselected stage III NSCLC, thoracic RT plus concurrent and consolidative durvalumab is associated with high-grade toxicity and early disease progression.Copyright © 2024. Published by Elsevier Inc.