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Phase II trial of bevacizumab and sorafenib in recurrent ovarian cancer patients with or without prior-bevacizumab treatment
- Source :
- Gynecol Oncol
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Objective 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). Methods This phase II study tested bevacizumab plus sorafenib in two cohorts; bevacizumab-naive 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). Results 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). Conclusions 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.
- Subjects :
- Adult
0301 basic medicine
Sorafenib
Oncology
medicine.medical_specialty
Bevacizumab
Phases of clinical research
Article
Drug Administration Schedule
03 medical and health sciences
0302 clinical medicine
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Clinical endpoint
Humans
Adverse effect
Response Evaluation Criteria in Solid Tumors
Aged
Ovarian Neoplasms
Dose-Response Relationship, Drug
business.industry
Interleukin-8
Obstetrics and Gynecology
Middle Aged
medicine.disease
Exceptional Responder
Progression-Free Survival
Clinical trial
030104 developmental biology
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Female
Neoplasm Recurrence, Local
Ovarian cancer
business
Follow-Up Studies
medicine.drug
Subjects
Details
- ISSN :
- 00908258
- Volume :
- 159
- Database :
- OpenAIRE
- Journal :
- Gynecologic Oncology
- Accession number :
- edsair.doi.dedup.....a24a71b18a7423dfd1467419a2c46677