학술논문
Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial
Document Type
article
Author
Monjazeb, Arta M; Daly, Megan E; Luxardi, Guillaume; Maverakis, Emanual; Merleev, Alexander A; Marusina, Alina I; Borowsky, Alexander; Mirhadi, Amin; Shiao, Stephen L; Beckett, Laurel; Chen, Shuai; Eastham, David; Li, Tianhong; Vick, Logan V; McGee, Heather M; Lara, Frances; Garcia, Leslie; Morris, Leigh Anne; Canter, Robert J; Riess, Jonathan W; Schalper, Kurt A; Murphy, William J; Kelly, Karen
Source
Nature Communications. 14(1)
Subject
Language
Abstract
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.