[PMID]: | 29059426 |
[Au] Autor: | Bais C; Mueller B; Brady MF; Mannel RS; Burger RA; Wei W; Marien KM; Kockx MM; Husain A; Birrer MJ; NRG Oncology/Gynecologic Oncology Group |
[Ad] Endereço: | Genentech Inc., South San Francisco, CA; F Hoffmann-La Roche Ltd, Basel, Switzerland; NRG Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY; University of Oklahoma, Oklahoma City, OK; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Penns |
[Ti] Título: | Tumor Microvessel Density as a Potential Predictive Marker for Bevacizumab Benefit: GOG-0218 Biomarker Analyses. |
[So] Source: | J Natl Cancer Inst;109(11), 2017 Nov 01. |
[Is] ISSN: | 1460-2105 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Background: Combining bevacizumab with frontline chemotherapy statistically significantly improved progression-free survival (PFS) but not overall survival (OS) in the phase III GOG-0218 trial. Evaluation of candidate biomarkers was an exploratory objective. Methods: Patients with stage III (incompletely resected) or IV ovarian cancer were randomly assigned to receive six chemotherapy cycles with placebo or bevacizumab followed by single-agent placebo or bevacizumab. Five candidate tumor biomarkers were assessed by immunohistochemistry. The biomarker-evaluable population was categorized into high or low biomarker-expressing subgroups using median and quartile cutoffs. Associations between biomarker expression and efficacy were analyzed. All statistical tests were two-sided. Results: The biomarker-evaluable population (n = 980) comprising 78.5% of the intent-to-treat population had representative baseline characteristics and efficacy outcomes. Neither prognostic nor predictive associations were seen for vascular endothelial growth factor (VEGF) receptor-2, neuropilin-1, or MET. Higher microvessel density (MVD; measured by CD31) showed predictive value for PFS (hazard ratio [HR] for bevacizumab vs placebo = 0.40, 95% confidence interval [CI] = 0.29 to 0.54, vs 0.80, 95% CI = 0.59 to 1.07, for high vs low MVD, respectively, P interaction = .003) and OS (HR = 0.67, 95% CI = 0.51 to 0.88, vs 1.10, 95% CI = 0.84 to 1.44, P interaction = .02). Tumor VEGF-A was not predictive for PFS but showed potential predictive value for OS using a third-quartile cutoff for high VEGF-A expression. Conclusions: These retrospective tumor biomarker analyses suggest a positive association between density of vascular endothelial cells (the predominant cell type expressing VEGF receptors) and tumor VEGF-A levels and magnitude of bevacizumab effect in ovarian cancer. The potential predictive value of MVD (CD31) and tumor VEGF-A is consistent with a mechanism of action driven by VEGF-A signaling blockade. |
[Mh] Termos MeSH primário: |
Inibidores da Angiogênese/uso terapêutico Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico Bevacizumab/uso terapêutico Biomarcadores Tumorais/análise Neoplasias Ovarianas/irrigação sanguínea Neoplasias Ovarianas/tratamento farmacológico
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[Mh] Termos MeSH secundário: |
Adulto Idoso Idoso de 80 Anos ou mais Biomarcadores Tumorais/metabolismo Carboplatina/administração & dosagem Intervalos de Confiança Intervalo Livre de Doença Método Duplo-Cego Esquema de Medicação Feminino Seres Humanos Análise de Intenção de Tratamento Microvasos Meia-Idade Neuropilina-1/metabolismo Neoplasias Ovarianas/metabolismo Neoplasias Ovarianas/patologia Paclitaxel/administração & dosagem Molécula-1 de Adesão Celular Endotelial de Plaquetas/análise Proteínas Proto-Oncogênicas c-met/metabolismo Estudos Retrospectivos Fator A de Crescimento do Endotélio Vascular/metabolismo Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
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[Pt] Tipo de publicação: | CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL |
[Nm] Nome de substância:
| 0 (Angiogenesis Inhibitors); 0 (Biomarkers, Tumor); 0 (Platelet Endothelial Cell Adhesion Molecule-1); 0 (Vascular Endothelial Growth Factor A); 144713-63-3 (Neuropilin-1); 2S9ZZM9Q9V (Bevacizumab); BG3F62OND5 (Carboplatin); EC 2.7.10.1 (MET protein, human); EC 2.7.10.1 (Proto-Oncogene Proteins c-met); EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2); P88XT4IS4D (Paclitaxel) |
[Em] Mês de entrada: | 1711 |
[Cu] Atualização por classe: | 171117 |
[Lr] Data última revisão:
| 171117 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 171024 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1093/jnci/djx066 |
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