阿替葛利单抗联合立体定向放射治疗对早期非小细胞肺癌患者的治疗效果：多机构I期临床试验。
Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial.
发表日期：2023 Sep 02
作者：
Arta M Monjazeb, Megan E Daly, Guillaume Luxardi, Emanual Maverakis, Alexander A Merleev, Alina I Marusina, Alexander Borowsky, Amin Mirhadi, Stephen L Shiao, Laurel Beckett, Shuai Chen, David Eastham, Tianhong Li, Logan V Vick, Heather M McGee, Frances Lara, Leslie Garcia, Leigh Anne Morris, Robert J Canter, Jonathan W Riess, Kurt A Schalper, William J Murphy, Karen Kelly
来源：
Cellular & Molecular Immunology
摘要：
立体定向消融放射治疗（SABR）是医学上无法手术的早期非小细胞肺癌（NSCLC）的标准护理模式。其中的三分之一患者病情恶化，且很少使用化疗。我们质疑是否在标准护理SABR的基础上加入免疫检查点抑制剂（ICI）阿特珠单抗能够改善治疗效果。我们开展了一项多机构单臂I期研究（NCT02599454），纳入了20名患者，主要终点为最大耐受剂量（MTD）；次要终点为安全性、疗效性和探索性相关机制。治疗耐受性良好，阿特珠单抗的完整剂量为MTD（1200mg）。疗效信号包括17％的患者在ICI的两个周期后（SABR开始之前）出现早期反应。功能适应性免疫的生物标志物，包括肿瘤中T细胞的活化以及循环T细胞对离体刺激的反应，对治疗益处具有高度预测性。这些结果需要验证，并正在进行三期随机试验中进行测试。© 2023. Springer Nature Limited.
Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC). One third of patients progress and chemotherapy is rarely used in this population. We questioned if addition of the immune-checkpoint-inhibitor (ICI) atezolizumab to standard-of-care SABR can improve outcomes. We initiated a multi-institutional single-arm phase I study (NCT02599454) enrolling twenty patients with the primary endpoint of maximum tolerated dose (MTD); secondary endpoints of safety and efficacy; and exploratory mechanistic correlatives. Treatment is well tolerated and full dose atezolizumab (1200 mg) is the MTD. Efficacy signals include early responses (after 2 cycles of ICI, before initiation of SABR) in 17% of patients. Biomarkers of functional adaptive immunity, including T cell activation in the tumor and response to ex-vivo stimulation by circulating T cells, are highly predictive of benefit. These results require validation and are being tested in a phase III randomized trial.© 2023. Springer Nature Limited.