Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant
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Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant. / Wimberger, Pauline; Gerber, Mara Julia; Pfisterer, Jacobus; Erdmann, Kati; Füssel, Susanne; Link, Theresa; du Bois, Andreas; Kommoss, Stefan; Heitz, Florian; Sehouli, Jalid; Kimmig, Rainer; de Gregorio, Nikolaus; Schmalfeldt, Barbara; Park-Simon, Tjoung-Won; Baumann, Klaus; Hilpert, Felix; Grube, Marcel; Schröder, Willibald; Burges, Alexander; Belau, Antje; Hanker, Lars; Kuhlmann, Jan Dominik.
In: CLIN CANCER RES, Vol. 28, No. 21, 01.11.2022, p. 4660-4668.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant
AU - Wimberger, Pauline
AU - Gerber, Mara Julia
AU - Pfisterer, Jacobus
AU - Erdmann, Kati
AU - Füssel, Susanne
AU - Link, Theresa
AU - du Bois, Andreas
AU - Kommoss, Stefan
AU - Heitz, Florian
AU - Sehouli, Jalid
AU - Kimmig, Rainer
AU - de Gregorio, Nikolaus
AU - Schmalfeldt, Barbara
AU - Park-Simon, Tjoung-Won
AU - Baumann, Klaus
AU - Hilpert, Felix
AU - Grube, Marcel
AU - Schröder, Willibald
AU - Burges, Alexander
AU - Belau, Antje
AU - Hanker, Lars
AU - Kuhlmann, Jan Dominik
N1 - ©2022 American Association for Cancer Research.
PY - 2022/11/1
Y1 - 2022/11/1
N2 - PURPOSE: The identification of a robust IHC marker to predict the response to antiangiogenic bevacizumab in ovarian cancer is of high clinical interest. VEGF-A, the molecular target of bevacizumab, is expressed as multiple isoforms with pro- or antiangiogenic properties, of which VEGF-A165b is the most dominant antiangiogenic isoform. The balance of VEGF-A isoforms is closely related to the angiogenic capacity of a tumor and may define its vulnerability to antiangiogenic therapy. We investigated whether the expression of VEGF-A165b could be related to the effect of bevacizumab in advanced ovarian cancer patients.EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tissues from 413 patients of the ICON7 multicenter phase III trial, treated with standard platinum-based chemotherapy with or without bevacizumab, were probed for VEGF-A165b expression by IHC.RESULTS: In patients with low VEGF-A165b expression, the addition of bevacizumab to standard platinum-based chemotherapy significantly improved progression-free (HR: 0.727; 95% CI, 0.538-0.984; P = 0.039) and overall survival (HR: 0.662; 95% CI, 0.458-0.958; P = 0.029). Multivariate analysis showed that the addition of bevacizumab in low VEGF-A165b-expressing patients conferred significant improvements in progression-free survival (HR: 0.610; 95% CI, 0.446-0.834; P = 0.002) and overall survival (HR: 0.527; 95% CI, 0.359-0.775; P = 0.001), independently from established risk factors.CONCLUSIONS: We demonstrate for the first time that bevacizumab may differentially improve the prognosis of advanced ovarian cancer patients with low expression of VEGF-A165b, an antiangiogenic VEGF-A splice variant. We envision that this novel biomarker could be implemented into routine diagnostics and may have direct clinical implications for guiding bevacizumab-related treatment decisions in advanced ovarian cancer patients.
AB - PURPOSE: The identification of a robust IHC marker to predict the response to antiangiogenic bevacizumab in ovarian cancer is of high clinical interest. VEGF-A, the molecular target of bevacizumab, is expressed as multiple isoforms with pro- or antiangiogenic properties, of which VEGF-A165b is the most dominant antiangiogenic isoform. The balance of VEGF-A isoforms is closely related to the angiogenic capacity of a tumor and may define its vulnerability to antiangiogenic therapy. We investigated whether the expression of VEGF-A165b could be related to the effect of bevacizumab in advanced ovarian cancer patients.EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tissues from 413 patients of the ICON7 multicenter phase III trial, treated with standard platinum-based chemotherapy with or without bevacizumab, were probed for VEGF-A165b expression by IHC.RESULTS: In patients with low VEGF-A165b expression, the addition of bevacizumab to standard platinum-based chemotherapy significantly improved progression-free (HR: 0.727; 95% CI, 0.538-0.984; P = 0.039) and overall survival (HR: 0.662; 95% CI, 0.458-0.958; P = 0.029). Multivariate analysis showed that the addition of bevacizumab in low VEGF-A165b-expressing patients conferred significant improvements in progression-free survival (HR: 0.610; 95% CI, 0.446-0.834; P = 0.002) and overall survival (HR: 0.527; 95% CI, 0.359-0.775; P = 0.001), independently from established risk factors.CONCLUSIONS: We demonstrate for the first time that bevacizumab may differentially improve the prognosis of advanced ovarian cancer patients with low expression of VEGF-A165b, an antiangiogenic VEGF-A splice variant. We envision that this novel biomarker could be implemented into routine diagnostics and may have direct clinical implications for guiding bevacizumab-related treatment decisions in advanced ovarian cancer patients.
KW - Humans
KW - Female
KW - Bevacizumab
KW - Vascular Endothelial Growth Factor A/genetics
KW - Angiogenesis Inhibitors/therapeutic use
KW - Prognosis
KW - Protein Isoforms/genetics
KW - Carcinoma, Ovarian Epithelial
KW - Ovarian Neoplasms/drug therapy
U2 - 10.1158/1078-0432.CCR-22-1326
DO - 10.1158/1078-0432.CCR-22-1326
M3 - SCORING: Journal article
C2 - 36001383
VL - 28
SP - 4660
EP - 4668
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 21
ER -
