Zhang Yuanyuan, Iyengar Puneeth, Montalvo Steven, Westover Kenneth D, Rashdan Sawsan, Donthireddy Kavitha, Kim James, Dowell Jonathan E, Drapkin Benjamin, Bhalla Sheena, Chukwuma Christian, Nadeem Urooba, Ahn Chul, Timmerman Robert D, Gerber David E
Departments of Radiation Oncology, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.
Departments of Radiation Oncology, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.
Int J Radiat Oncol Biol Phys. 2025 Jan 1;121(1):68-74. doi: 10.1016/j.ijrobp.2024.07.2333. Epub 2024 Aug 13.
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.
巩固性使用度伐利尤单抗，一种抗程序性死亡配体1（PDL1）免疫检查点抑制剂，在同步放化疗后使用可改善局部晚期非小细胞肺癌（NSCLC）患者的预后，且不会大幅增加毒性。我们研究了一种同步和巩固性使用度伐利尤单抗的无化疗胸部放疗（RT）方案。
这项单臂2期试验纳入了III期NSCLC患者（无论肿瘤PDL1表达情况如何），东部肿瘤协作组（ECOG）体能状态为0 - 1，肺功能良好，且RT野符合标准器官限制。参与者在接受胸部RT（60 Gy，分30次）的同时接受2个周期的度伐利尤单抗（每4周1500 mg），随后接受多达13个周期的巩固性度伐利尤单抗治疗。
在招募了10名患者后，由于临床结果不佳，试验提前结束。中位随访12个月时，5名患者疾病进展，8名患者死亡。6名患者发生了15起与治疗相关的≥3级事件，包括巩固期1例4级急性肾损伤和2例致命肺部事件。1例致命肺部事件发生在同步治疗期的一名现吸烟者中；另1例发生在巩固性度伐利尤单抗的第一个周期后。12个月无进展生存的主要终点为20%（PDL1≥1%者为50%，PDL1不可用或<1%者为0%）。PDL1≥1%、<1%和不可用患者的中位总生存期分别未达到、10.5个月和7个月。
在未选择PDL1的III期NSCLC患者中，胸部放疗加同步和巩固性度伐利尤单抗与高级别毒性和早期疾病进展相关。
