Phase II trial of bevacizumab and sorafenib in recurrent ovarian cancer patients with or without prior-bevacizumab treatment.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Bevacizumab
/ administration & dosage
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Resistance, Neoplasm
Female
Follow-Up Studies
Humans
Interleukin-8
/ blood
Middle Aged
Neoplasm Recurrence, Local
/ blood
Ovarian Neoplasms
/ drug therapy
Progression-Free Survival
Response Evaluation Criteria in Solid Tumors
Sorafenib
/ administration & dosage
Bevacizumab
Clinical trial
Ovarian cancer
Post-bevacizumab
Sorafenib
Journal
Gynecologic oncology
ISSN: 1095-6859
Titre abrégé: Gynecol Oncol
Pays: United States
ID NLM: 0365304
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
08
06
2020
accepted:
21
07
2020
pubmed:
5
8
2020
medline:
15
4
2021
entrez:
5
8
2020
Statut:
ppublish
Résumé
To examine whether blocking multiple points of the angiogenesis pathway by addition of sorafenib, a multi-kinase inhibitor against VEGFR2/3, Raf, c-Kit, and PDGFR, to bevacizumab would yield clinical activity in ovarian cancer (OvCa). This phase II study tested bevacizumab plus sorafenib in two cohorts; bevacizumab-naïve and bevacizumab-exposed patients. Bevacizumab (5 mg/kg IV every 2 weeks) was given with sorafenib 200 mg bid 5 days-on/2 days-off. The primary objective was response rate using a Simon two-stage optimal design. Progression-free survival (PFS) and toxicity were the secondary endpoints. Exploratory correlative studies included plasma cytokine concentrations, tissue proteomics and dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI). Between March 2007 and August 2012, 54 women were enrolled, 41 bevacizumab-naive and 13 bevacizumab-prior, with median 5 (2-9) and 6 (5-9) prior systemic therapies, respectively. Nine of 35 (26%) evaluable bevacizumab-naive patients attained partial responses (PR), and 18 had stable disease (SD) ≥ 4 months. No responses were seen in the bevacizumab-prior group and 7 (54%) patients had SD ≥ 4 months, including one exceptional responder with SD of 27 months. The overall median PFS was 5.5 months (95%CI: 4.0-6.8 months). Treatment-related grade 3/4 adverse events (≥5%) included hypertension (17/54 [31%]; grade 3 in 16 patients and grade 4 in one patient) and venous thrombosis or pulmonary embolism (5/54 [9%]; grade 3 in 4 patients and grade 4 in one patient). Pretreatment low IL8 concentration was associated with PFS ≥ 4 months (p = .031). The bevacizumab and sorafenib combination did not meet the pre-specified primary endpoint although some clinical activity was seen in heavily-pretreated bevacizumab-naive OvCa patients with platinum-resistant disease. Anticipated class toxicities required close monitoring and dose modifications.
Identifiants
pubmed: 32747013
pii: S0090-8258(20)33677-5
doi: 10.1016/j.ygyno.2020.07.031
pmc: PMC7541580
mid: NIHMS1616959
pii:
doi:
Substances chimiques
CXCL8 protein, human
0
Interleukin-8
0
Bevacizumab
2S9ZZM9Q9V
Sorafenib
9ZOQ3TZI87
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
88-94Subventions
Organisme : Intramural NIH HHS
ID : Z99 CA999999
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC011525
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Competing Interest All authors declared no conflicts of interest.
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