Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma.
Adult
Aged
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Bevacizumab
/ administration & dosage
Biomarkers, Tumor
/ blood
Brain Neoplasms
/ blood
Drug Monitoring
/ methods
Female
Glioblastoma
/ blood
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
/ blood
Prognosis
Progression-Free Survival
Prospective Studies
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 02 2021
15 02 2021
Historique:
received:
26
06
2020
revised:
31
08
2020
accepted:
10
11
2020
pubmed:
18
11
2020
medline:
21
1
2022
entrez:
17
11
2020
Statut:
ppublish
Résumé
VEGF is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase II study of pembrolizumab alone or with bevacizumab in recurrent glioblastoma. Eighty bevacizumab-naïve patients with recurrent glioblastoma were randomized to pembrolizumab with bevacizumab (cohort A, Pembrolizumab alone or with bevacizumab was well tolerated but of limited benefit. For cohort A, PFS-6 was 26.0% [95% confidence interval (CI), 16.3-41.5], median overall survival (OS) was 8.8 months (95% CI, 7.7-14.2), objective response rate (ORR) was 20%, and median duration of response was 48 weeks. For cohort B, PFS-6 was 6.7% (95% CI, 1.7-25.4), median OS was 10.3 months (95% CI, 8.5-12.5), and ORR was 0%. Tumor immune markers were not associated with OS, but worsened OS correlated with baseline dexamethasone use and increased posttherapy plasma VEGF (cohort A) and mutant Pembrolizumab was ineffective as monotherapy and with bevacizumab for recurrent glioblastoma. The infrequent radiographic responses to combinatorial therapy were durable. Tumor immune biomarkers did not predict outcome. Baseline dexamethasone use and tumor MGMT warrant further study as potential biomarkers in glioblastoma immunotherapy trials.
Identifiants
pubmed: 33199490
pii: 1078-0432.CCR-20-2500
doi: 10.1158/1078-0432.CCR-20-2500
pmc: PMC8284901
mid: NIHMS1716816
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biomarkers, Tumor
0
Bevacizumab
2S9ZZM9Q9V
pembrolizumab
DPT0O3T46P
Types de publication
Clinical Trial, Phase II
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1048-1057Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA208205
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197743
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197442
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
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