关于PDL1未筛选的III期非小细胞肺癌同时放化疗结合Durvalumab的安全性与疗效简要报告

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

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS

影响因子:6.5

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

DOI: 10.1016/j.ijrobp.2024.07.2333

摘要

在局部晚期非小细胞肺癌（NSCLC）中，合并Durvalumab（一种抗程序性死亡配体1（PDL1）免疫检查点抑制剂）在放化疗基础上进行巩固治疗可改善患者预后，但毒性反应有所增加。本研究探讨了一种无化疗方案的胸部放疗结合Durvalumab的方案。该单臂第二阶段试验纳入所有PDL1表达水平未筛选的III期NSCLC患者，符合ECOG性能状态0-1，肺功能良好，放疗场符合器官限制。患者接受2周期Durvalumab（每4周1500 mg）同时进行60 Gy/30次的胸部放疗，之后最多13个周期的巩固Durvalumab。10例患者入组后，由于临床结果不佳，试验提前终止。随访中位时间12个月，疾病进展患者5例，死亡8例。有6例患者出现15例与治疗相关的≥3级事件，包括1例急性肾损伤（4级）和2例致命性肺部事件。一次致命肺部事件发生在活动吸烟者的同时期，另一发生在第一周期后。12个月的无进展生存率为20%（PDL1≥1%的为50%，未筛选或<1%的为0%）。中位总生存期尚未达到，分别为10.5和7个月，PDL1≥1%、<1%和未筛选的患者。总体而言，未筛选的III期NSCLC患者中，胸部放疗结合Durvalumab存在较高的高等级毒性和早期疾病进展风险。

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.