Predictive and prognostic angiogenic markers in a gynecologic oncology group phase II trial of bevacizumab in recurrent and persistent ovarian or peritoneal cancer.
OBJECTIVE
Potential predictive/prognostic angiogenic markers were prospectively examined in a phase II trial of bevacizumab in epithelial ovarian cancer (EOC)/primary peritoneal cancer (PPC).


METHODS
Recurrent/persistent EOC/PPC patients were treated with bevacizumab (15 mg/kg IV q21days) until disease progression. Validated-immunohistochemistry (IHC) assays were performed on pre-cycle 1/4 tumor biopsies for CD31-microvessel density (MVD), VEGF-histoscore (HS), p53-HS, and TSP1 image analysis score (IA). Pre-cycle 1/4 serum and plasma VEGF were quantified using a validated-ELISA.


RESULTS
CD31-MVD and serum VEGF, evaluated pre-cycle 1 in 41/61 and 51/61 eligible patients, respectively, did not appear to be correlated. High CD31-MVD, categorized at the median, appeared to be associated with tumor response, a 13-month shorter median survival, and an increased risk of death (unadjusted hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.067-4.467). In addition, each standard deviation (SD) increase in CD31-MVD appeared to be associated with worse survival in unadjusted and adjusted analyses. IHC and plasma biomarkers did not change with bevacizumab treatment except for serum VEGF, which appeared to decrease during bevacizumab treatment. This decrease was not associated with response. High pre-cycle 1 serum VEGF, categorized at the median, was associated with 22-month shorter median survival and an increased risk of death (unadjusted HR = 2.7, 95% CI = 1.369-5.191). Categorized p53 appeared to be associated with unadjusted survival and each SD increase in TSP1-IA appeared to be associated with a decreased risk of progression in unadjusted and adjusted analyses.


CONCLUSIONS
Despite the limitations in sample size and exploratory nature of the study, angiogenic markers in tumor and serum may provide prognostic value in recurrent/persistent EOC/PPC, and are being prospectively evaluated in the GOG phase III trial of carboplatin, paclitaxel and bevacizumab/placebo in previously untreated EOC/PPC.
Han
Ernest S
ES
University of California Irvine, Orange, CA, USA.
Burger
Robert A
RA
Darcy
Kathleen M
KM
Sill
Michael W
MW
Randall
Leslie M
LM
Chase
Dana
D
Parmakhtiar
Basmina
B
Monk
Bradley J
BJ
Greer
Benjamin E
BE
Connelly
Patrick
P
Degeest
Koen
K
Fruehauf
John P
JP
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000098:blood supply / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000097:blood / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000098:blood supply / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000097:blood / Q000098:blood supply / Q000188:drug therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D011379:Prognosis; D011446:Prospective Studies; D019700:Thrombospondin 1 / Q000097:blood*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C495901:TP53 protein, human; D019700:Thrombospondin 1; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab