| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-14 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-40813-w |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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