Pembrolizumab in brain metastases of diverse histologies: phase 2 trial results.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
08
03
2023
accepted:
09
05
2023
medline:
21
7
2023
pubmed:
3
6
2023
entrez:
2
6
2023
Statut:
ppublish
Résumé
Brain metastases (BMs) are an emerging challenge in oncology due to increasing incidence and limited treatments. Here, we present results of a single-arm, open-label, phase 2 trial evaluating intracranial efficacy of pembrolizumab, a programmed cell death protein 1 inhibitor, in 9 patients with untreated BMs (cohort A) and 48 patients with recurrent and progressive BMs (cohort B) across different histologies. The primary endpoint was the proportion of patients achieving intracranial benefit, defined by complete response, partial response or stable disease. The primary endpoint was met with an intracranial benefit rate of 42.1% (90% confidence interval (CI): 31-54%). The median overall survival, a secondary endpoint, was 8.0 months (90% CI: 5.5-8.7 months) across both cohorts, 6.5 months (90% CI: 4.5-18.7 months) for cohort A and 8.1 months (90% CI: 5.3-9.6 months) for cohort B. Seven patients (12.3%), encompassing breast, melanoma and sarcoma histologies, had overall survival greater than 2 years. Thirty patients (52%; 90% CI: 41-64%) had one or more grade-3 or higher adverse events that were at least possibly treatment related. Two patients had grade-4 adverse events (cerebral edema) that were deemed at least possibly treatment related. These results suggest that programmed cell death protein 1 blockade may benefit a select group of patients with BMs, and support further studies to identify biomarkers and mechanisms of resistance. ClinicalTrials.gov identifier: NCT02886585.
Identifiants
pubmed: 37268724
doi: 10.1038/s41591-023-02392-7
pii: 10.1038/s41591-023-02392-7
pmc: PMC10644912
mid: NIHMS1939002
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
pembrolizumab
DPT0O3T46P
Banques de données
ClinicalTrials.gov
['NCT02886585']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1728-1737Subventions
Organisme : NCI NIH HHS
ID : R01 CA211238
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227156
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA244975
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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