A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
26
02
2022
accepted:
21
09
2022
pubmed:
27
11
2022
medline:
30
11
2022
entrez:
26
11
2022
Statut:
ppublish
Résumé
Five-year survival for human papilloma virus-unrelated head and neck squamous cell carcinomas remain below 50%. We assessed the safety of administering combination hypofractionated stereotactic body radiation therapy with single-dose durvalumab (anti-PD-L1) neoadjuvantly (n = 21) ( NCT03635164 ). The primary endpoint of the study was safety, which was met. Secondary endpoints included radiographic, pathologic and objective response; locoregional control; progression-free survival; and overall survival. Among evaluable patients at an early median follow-up of 16 months (448 d or 64 weeks), overall survival was 80.1% with 95% confidence interval (95% CI) (62.0%, 100.0%), locoregional control and progression-free survival were 75.8% with 95% CI (57.5%, 99.8%), and major pathological response or complete response was 75% with 95% exact CI (51.6%, 100.0%). For patients treated with 24 Gy, 89% with 95% CI (57.1%, 100.0%) had MPR or CR. Using high-dimensional multi-omics and spatial data as well as biological correlatives, we show that responders had: (1) an increase in effector T cells; (2) a decrease in immunosuppressive cells; and (3) an increase in antigen presentation post-treatment.
Identifiants
pubmed: 36434392
doi: 10.1038/s43018-022-00450-6
pii: 10.1038/s43018-022-00450-6
pmc: PMC9701140
doi:
Substances chimiques
durvalumab
28X28X9OKV
Banques de données
ClinicalTrials.gov
['NCT03635164']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1300-1317Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL146442
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148151
Pays : United States
Organisme : NIDCR NIH HHS
ID : F31 DE029997
Pays : United States
Organisme : NIGMS NIH HHS
ID : RM1 GM131968
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
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