Neoadjuvant Cabozantinib and Nivolumab Converts Locally Advanced HCC into Resectable Disease with Enhanced Antitumor Immunity.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
entrez:
19
11
2021
pubmed:
20
11
2021
medline:
20
11
2021
Statut:
ppublish
Résumé
A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC), but most patients are not candidates for resection and most resected HCCs eventually recur. Until recently, neoadjuvant systemic therapy for HCC has been limited by a lack of effective systemic agents. Here, in a single arm phase 1b study, we evaluated the feasibility of neoadjuvant cabozantinib and nivolumab in patients with HCC including patients outside of traditional resection criteria (NCT03299946). Of 15 patients enrolled, 12 (80%) underwent successful margin negative resection, and 5/12 (42%) patients had major pathologic responses. In-depth biospecimen profiling demonstrated an enrichment in T effector cells, as well as tertiary lymphoid structures, CD138+ plasma cells, and a distinct spatial arrangement of B cells in responders as compared to non-responders, indicating an orchestrated B-cell contribution to antitumor immunity in HCC.
Identifiants
pubmed: 34796337
doi: 10.1038/s43018-021-00234-4
pmc: PMC8594857
mid: NIHMS1714155
pii: 10.1038/s43018-021-00234-4
doi:
Substances chimiques
Anilides
0
Pyridines
0
cabozantinib
1C39JW444G
Nivolumab
31YO63LBSN
Banques de données
ClinicalTrials.gov
['NCT03299946']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
891-903Subventions
Organisme : NCI NIH HHS
ID : R50 CA243627
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA212007
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA253403
Pays : United States
Organisme : NINDS NIH HHS
ID : K99 NS122085
Pays : United States
Déclaration de conflit d'intérêts
Competing Interests The remaining authors declare no competing interests.
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