Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant

Pauline Wimberger; Mara Julia Gerber; Jacobus Pfisterer; Kati Erdmann; Susanne Füssel; Theresa Link; Andreas du Bois; Stefan Kommoss; Florian Heitz; Jalid Sehouli; Rainer Kimmig; Nikolaus de Gregorio; Barbara Schmalfeldt; Tjoung-Won Park-Simon; Klaus Baumann; Felix Hilpert; Marcel Grube; Willibald Schröder; Alexander Burges; Antje Belau; Lars Hanker; Jan Dominik Kuhlmann

doi:10.1158/1078-0432.CCR-22-1326

Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant

Pauline Wimberger, Mara Julia Gerber, Jacobus Pfisterer, Kati Erdmann, Susanne Füssel, Theresa Link, Andreas du Bois, Stefan Kommoss, Florian Heitz, Jalid Sehouli, Rainer Kimmig, Nikolaus de Gregorio, Barbara Schmalfeldt, Tjoung-Won Park-Simon, Klaus Baumann, Felix Hilpert, Marcel Grube, Willibald Schröder, Alexander Burges, Antje BelauLars Hanker, Jan Dominik Kuhlmann

Klinik für Frauenheilkunde und Geburtshilfe

5 Zitate (Scopus)

Abstract

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.

Originalsprache	Englisch
Zeitschrift	Clinical cancer research : an official journal of the American Association for Cancer Research
Jahrgang	28
Ausgabenummer	21
Seiten (von - bis)	4660-4668
Seitenumfang	9
ISSN	1078-0432
DOIs	https://doi.org/10.1158/1078-0432.CCR-22-1326
Publikationsstatus	Veröffentlicht - 01.11.2022

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Strategische Forschungsbereiche und Zentren

Zentren: Universitäres Cancer Center Schleswig-Holstein (UCCSH)
Profilbereich: Lübeck Integrated Oncology Network (LION)

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10.1158/1078-0432.CCR-22-1326

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Wimberger, P., Gerber, M. J., Pfisterer, J., Erdmann, K., Füssel, S., Link, T., du Bois, A., Kommoss, S., Heitz, F., Sehouli, J., Kimmig, R., de Gregorio, N., Schmalfeldt, B., Park-Simon, T.-W., Baumann, K., Hilpert, F., Grube, M., Schröder, W., Burges, A., ... Kuhlmann, J. D. (2022). Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant. Clinical cancer research : an official journal of the American Association for Cancer Research, 28(21), 4660-4668. https://doi.org/10.1158/1078-0432.CCR-22-1326

Wimberger, Pauline ; Gerber, Mara Julia ; Pfisterer, Jacobus et al. / Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant. in: Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 ; Jahrgang 28, Nr. 21. S. 4660-4668.

@article{5b8d78767f6541ceaf7cb8d2ac89ab42,

title = "Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant",

abstract = "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.",

author = "Pauline Wimberger and Gerber, \{Mara Julia\} and Jacobus Pfisterer and Kati Erdmann and Susanne F{\"u}ssel and Theresa Link and \{du Bois\}, Andreas and Stefan Kommoss and Florian Heitz and Jalid Sehouli and Rainer Kimmig and \{de Gregorio\}, Nikolaus and Barbara Schmalfeldt and Tjoung-Won Park-Simon and Klaus Baumann and Felix Hilpert and Marcel Grube and Willibald Schr{\"o}der and Alexander Burges and Antje Belau and Lars Hanker and Kuhlmann, \{Jan Dominik\}",

note = "{\textcopyright}2022 American Association for Cancer Research.",

year = "2022",

month = nov,

day = "1",

doi = "10.1158/1078-0432.CCR-22-1326",

language = "English",

volume = "28",

pages = "4660--4668",

journal = "Clinical cancer research : an official journal of the American Association for Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "21",

}

Wimberger, P, Gerber, MJ, Pfisterer, J, Erdmann, K, Füssel, S, Link, T, du Bois, A, Kommoss, S, Heitz, F, Sehouli, J, Kimmig, R, de Gregorio, N, Schmalfeldt, B, Park-Simon, T-W, Baumann, K, Hilpert, F, Grube, M, Schröder, W, Burges, A, Belau, A, Hanker, L & Kuhlmann, JD 2022, 'Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant', Clinical cancer research : an official journal of the American Association for Cancer Research, Jg. 28, Nr. 21, S. 4660-4668. https://doi.org/10.1158/1078-0432.CCR-22-1326

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 et al.
in: Clinical cancer research : an official journal of the American Association for Cancer Research, Jahrgang 28, Nr. 21, 01.11.2022, S. 4660-4668.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

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

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.

U2 - 10.1158/1078-0432.CCR-22-1326

DO - 10.1158/1078-0432.CCR-22-1326

M3 - Journal articles

C2 - 36001383

SN - 1078-0432

VL - 28

SP - 4660

EP - 4668

JO - Clinical cancer research : an official journal of the American Association for Cancer Research

JF - Clinical cancer research : an official journal of the American Association for Cancer Research

IS - 21

ER -

Wimberger P, Gerber MJ, Pfisterer J, Erdmann K, Füssel S, Link T et al. Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant. Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 Nov 1;28(21):4660-4668. doi: 10.1158/1078-0432.CCR-22-1326

Bevacizumab May Differentially Improve Prognosis of Advanced Ovarian Cancer Patients with Low Expression of VEGF-A165b, an Antiangiogenic VEGF-A Splice Variant

Abstract

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