关于在PDL1未选择的III期非小细胞肺癌中，并发和巩固Durvalumab与胸腔辐射疗法的安全性和功效有关：简短报告
Concerning Safety and Efficacy of Concurrent and Consolidative Durvalumab With Thoracic Radiation Therapy in PDL1-Unselected Stage III Non-Small Cell Lung Cancer: Brief Report
影响因子:6.50000
分区:医学1区 Top / 肿瘤学2区 核医学2区
发表日期:2025 Jan 01
作者:
Yuanyuan Zhang, Puneeth Iyengar, Steven Montalvo, Kenneth D Westover, Sawsan Rashdan, Kavitha Donthireddy, James Kim, Jonathan E Dowell, Benjamin Drapkin, Sheena Bhalla, Christian Chukwuma, Urooba Nadeem, Chul Ahn, Robert D Timmerman, David E Gerber
摘要
在并发化学放疗后施用的抗编程死亡配体1（PDL1）免疫检查点抑制剂的巩固性死亡配体抑制剂可改善局部晚期非小细胞肺癌（NSCLC）患者的结局，而无需大大增加毒性。 We studied a chemotherapy-free regimen of thoracic radiation therapy (RT) with concurrent and consolidative durvalumab.This single-arm phase 2 trial enrolled patients with stage III NSCLC (regardless of tumor PDL1 expression), Eastern Cooperative Oncology Group (ECOG) performance status 0-1, adequate pulmonary function, and RT fields meeting standard organ constraints.参与者同时接受了2个周期的杜瓦卢马布（每4周1500 mg）（每4周1500 mg）（每30个分数为60 Gy），然后最多13个固结杜瓦卢马布的周期。招募了10例患者，该试验因临床不良而关闭，该试验被关闭。中位随访为12个月，有5例患者患有疾病进展，8例患者死亡。 6例患者经历了15例与治疗相关的≥3级事件，包括1级4级急性肾脏损伤和2次致命的肺部事件。活跃吸烟者的并发阶段发生了一项致命的肺事件。另一个发生在第一个巩固杜瓦卢马布的第一个周期之后。 12个月时无进展生存的主要终点为20％（PDL1≥1％，而PDL1不可用的PDL1≥1％或<1％）。对于PDL1≥1％，<1％和不可用的PDL1≥1％和7个月未达到中位总生存期。在PDL1未选择的III阶段NSCLC中，Thoracic RT Plus并发和辅助Durvalumab与高级毒性和早期疾病进展有关。
Abstract
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 radiation therapy (RT) with concurrent and consolidative durvalumab.This single-arm phase 2 trial enrolled patients with stage III NSCLC (regardless of tumor PDL1 expression), Eastern Cooperative Oncology Group (ECOG) performance status 0-1, adequate pulmonary function, and RT fields meeting standard organ constraints. Participants received 2 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 because of poor clinical outcomes. With a median follow-up of 12 months, 5 patients had disease progression and 8 patients died. Six patients experienced 15 treatment-related, grade ≥3 events, including 1 grade 4 acute kidney injury during consolidation and 2 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 at 12 months was 20% (50% for PDL1≥1% vs 0% for PDL1 unavailable or <1%). Median overall survival 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.