Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer.
Markers of bone metabolism
Journal
Clinical genitourinary cancer
ISSN: 1938-0682
Titre abrégé: Clin Genitourin Cancer
Pays: United States
ID NLM: 101260955
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
16
08
2019
revised:
21
10
2019
accepted:
28
10
2019
pubmed:
18
4
2020
medline:
16
6
2021
entrez:
18
4
2020
Statut:
ppublish
Résumé
Cabozantinib is active in advanced prostate cancer with improvement on bone scans in men on phase II trials. This trial evaluated the efficacy and changes in bone lesions in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabozantinib. Eligible patients with mCRPC involving bone underwent biopsy of a bone lesion followed by cabozantinib starting at 60 mg daily and continuing until progression or intolerable toxicity. The primary study endpoint was progression-free survival at 12 weeks. The bone lesion was rebiopsied at 6 weeks. Expression of CMET, phospho-CMET, and VEGFR2 was assayed by immunohistochemistry. Serum was obtained at baseline, and at 3, 6, and 12 weeks and assayed for bone remodeling markers. A total of 25 patients were enrolled: 22 were evaluable, and 3 were excluded before receiving cabozantinib. At 12 weeks, 17 (77%) of 22 patients had stable disease or better. The median time on treatment was 24 weeks (range, 3-112 weeks). The overall median progression-free survival was 43.7 weeks (95% confidence interval, 23.7-97.0 weeks). Eight (36%) of 22 patients had markedly reduced uptake on bone scan. Patients with significant response on bone scan had higher bone morphogenic protein-2 levels at baseline, stable N-telopeptides levels, increased vascular endothelial growth factor receptor 2 expression, and a trend towards increased phospho-CMET while on cabozantinib compared with patients with stable disease. Cabozantinib is active in men with mCRPC, inducing significant changes on bone scan in one-third of patients with changes in markers of bone formation and the tumor microenvironment.
Sections du résumé
BACKGROUND
Cabozantinib is active in advanced prostate cancer with improvement on bone scans in men on phase II trials. This trial evaluated the efficacy and changes in bone lesions in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabozantinib.
PATIENTS AND METHODS
Eligible patients with mCRPC involving bone underwent biopsy of a bone lesion followed by cabozantinib starting at 60 mg daily and continuing until progression or intolerable toxicity. The primary study endpoint was progression-free survival at 12 weeks. The bone lesion was rebiopsied at 6 weeks. Expression of CMET, phospho-CMET, and VEGFR2 was assayed by immunohistochemistry. Serum was obtained at baseline, and at 3, 6, and 12 weeks and assayed for bone remodeling markers.
RESULTS
A total of 25 patients were enrolled: 22 were evaluable, and 3 were excluded before receiving cabozantinib. At 12 weeks, 17 (77%) of 22 patients had stable disease or better. The median time on treatment was 24 weeks (range, 3-112 weeks). The overall median progression-free survival was 43.7 weeks (95% confidence interval, 23.7-97.0 weeks). Eight (36%) of 22 patients had markedly reduced uptake on bone scan. Patients with significant response on bone scan had higher bone morphogenic protein-2 levels at baseline, stable N-telopeptides levels, increased vascular endothelial growth factor receptor 2 expression, and a trend towards increased phospho-CMET while on cabozantinib compared with patients with stable disease.
CONCLUSIONS
Cabozantinib is active in men with mCRPC, inducing significant changes on bone scan in one-third of patients with changes in markers of bone formation and the tumor microenvironment.
Identifiants
pubmed: 32299729
pii: S1558-7673(19)30323-4
doi: 10.1016/j.clgc.2019.10.019
pmc: PMC8802308
mid: NIHMS1573464
pii:
doi:
Substances chimiques
Anilides
0
Pyridines
0
cabozantinib
1C39JW444G
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
332-339.e2Subventions
Organisme : NCI NIH HHS
ID : P01 CA093900
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA046592
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA186786
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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