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Predictive biomarkers bevacizumab

Kohei Shitara, Kimio Yonesaka, Tadamichi Denda, Kentaro Yamazaki, Toshikazu Moriwaki, Masahiro Tsuda, Toshimi Takano, Hiroyuki Okuda, Tomohiro Nishina, Kazuko Sakai, Kazuto Nishio, Shoji Tokunaga, Takeharu Yamanaka, Narikazu Boku, Ichinosuke Hyodo, Kei Muro
This randomized phase II trial compared panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) with bevacizumab plus FOLFIRI as second-line chemotherapy for wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) and to explore the values of oncogenes in circulating tumor DNA (ctDNA) and serum proteins as predictive biomarkers. Patients with WT KRAS exon 2 mCRC refractory to first-line chemotherapy containing oxaliplatin and bevacizumab were randomly assigned to panitumumab plus FOLFIRI or bevacizumab plus FOLFIRI...
October 6, 2016: Cancer Science
Emiliano Calvo, Manuela Schmidinger, Daniel Y C Heng, Viktor Grünwald, Bernard Escudier
Survival of patients with metastatic renal cell carcinoma (mRCC) has improved since the advent of targeted therapy. Approved agents include the multi-targeted tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib (approved in combination with everolimus), the anti-VEGF monoclonal antibody bevacizumab, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and the programmed death-1 (PD-1) targeted immune checkpoint inhibitor nivolumab...
September 10, 2016: Cancer Treatment Reviews
Hye Rim Cho, Bora Hong, Hyeonjin Kim, Chul-Kee Park, Sung-Hye Park, Sunghyouk Park, Seung Hong Choi
BCAT1 (branched-chain amino acid trasaminase1) expression is necessary for the progression of IDH1 wild-type (WT) glioblastoma multiforme (GBM), which is known to be associated with aggressive tumors. The purpose of our study is to investigate the bevacizumab resistance increased by the expression of BCAT1 in IDH1 WT GBM in a rat model, which was evaluated using DSC perfusion MRI. BCAT1 sh#1 inhibits cell proliferation and limits cell migration potential in vitro. In vivo MRI showed that the increase in both tumor volume and nCBV after bevacizumab treatment in IDH1 WT tumors was significantly higher compared with BCAT1 sh#1tumors...
September 8, 2016: Oncotarget
Sebastiano Buti, Alessandro Leonetti, Alice Dallatomasina, Melissa Bersanelli
INTRODUCTION: Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, and its pathogenesis is strictly related to altered cellular response to hypoxia, in which mTOR signaling pathway is implicated. Everolimus, an mTOR serine/threonine kinase inhibitor, represents a therapeutic option for the treatment of advanced RCC. AIM: The objective of this article is to review the evidence for the treatment of metastatic RCC with everolimus. EVIDENCE REVIEW: Everolimus was approved for second- and third-line therapy in patients with advanced RCC according to the results of a Phase III pivotal trial that demonstrated a benefit in median progression-free survival of ~2 months compared to placebo after failure of previous lines of therapy, of which at least one was an anti-VEGFR tyrosine kinase inhibitor (TKI)...
2016: Core Evidence
Madelon Q Wentink, Henk J Broxterman, Siu W Lam, Epie Boven, Maudy Walraven, Arjan W Griffioen, Roberto Pili, Hans J van der Vliet, Tanja D de Gruijl, Henk M W Verheul
BACKGROUND: Only a small proportion of patients respond to anti-VEGF therapy, pressing the need for a reliable biomarker that can identify patients who will benefit. We studied the biological activity of anti-VEGF antibodies in patients' blood during anti-VEGF therapy by using the Ba/F3-VEGFR2 cell line, which is dependent on VEGF for its growth. METHODS: Serum samples from 22 patients with cancer before and during treatment with bevacizumab were tested for their effect on proliferation of Ba/F3-VEGFR2 cells...
October 11, 2016: British Journal of Cancer
Analia Rodríguez Garzotto, C Vanesa Díaz-García, Alba Agudo-López, Elena Prieto García, Santiago Ponce, José A López-Martín, Luis Paz-Ares, Lara Iglesias, M Teresa Agulló-Ortuño
Tumor angiogenesis pathways have been identified as important therapeutic targets in non-small cell lung cancer. However, no biomarkers have been described as predictors of response to antiangiogenic therapy in these patients. In this study, plasma levels of VEGF, bFGF, E-selectin, and S-ICAM and gene expression profiles of peripheral blood mononuclear cells from non-small cell lung cancer patients treated with chemotherapy plus bevacizumab were analyzed before and after treatment. Values were correlated with clinicopathological characteristics and treatment response...
October 2016: Medical Oncology
David Molina, Julián Pérez-Beteta, Alicia Martínez-González, Juan M Sepúlveda, Sergi Peralta, Miguel J Gil-Gil, Gaspar Reynes, Ana Herrero, Ramón De Las Peñas, Raquel Luque, Jaume Capellades, Carmen Balaña, Víctor M Pérez-García
BACKGROUND: Antiangiogenic therapies for glioblastoma (GBM) such as bevacizumab (BVZ), have been unable to extend survival in large patient cohorts. However, a subset of patients having angiogenesis-dependent tumors might benefit from these therapies. Currently, there are no biomarkers allowing to discriminate responders from non-responders before the start of the therapy. METHODS: 40 patients from the randomized GENOM009 study complied the inclusion criteria (quality of images, clinical data available)...
2016: PloS One
Kristen K Ciombor, Richard M Goldberg
Angiogenesis is a complex biologic process critical to growth and proliferation of colorectal cancer. The safety and efficacy of various anti-angiogenic agents have been investigated in many treatment settings. Bevacizumab, an anti-vascular endothelial growth factor agent, has efficacy in both the first-line setting and beyond progression in metastatic colorectal cancer. The decoy vascular endothelial growth factor receptor aflibercept has been approved in combination with 5-fluorouracil, leucovorin and irinotecan-based chemotherapy in metastatic colorectal cancer patients whose disease has progressed on a prior oxaliplatin-based chemotherapy regimen...
December 2015: Current Colorectal Cancer Reports
Stefan Stremitzer, Wu Zhang, Dongyun Yang, Yan Ning, Yu Sunakawa, Satoshi Matsusaka, Anish Parekh, Satoshi Okazaki, Diana Hanna, Stephanie H Astrow, Miriana Moran, Jose Hernandez, Craig Stephens, Stefan J Scherer, Judith Stift, Friedrich Wrba, Thomas Gruenberger, Heinz-Josef Lenz
Angiogenesis-related gene expression is associated with the efficacy of anti-VEGF therapy. We tested whether intratumoral mRNA expression levels of genes involved in vascular morphogenesis and early vessel maturation predict response, recurrence-free survival (RFS), and overall survival (OS) in a unique cohort of patients with colorectal liver metastases (CLM) treated with bevacizumab-based chemotherapy followed by curative liver resection. Intratumoral mRNA was isolated from resected bevacizumab-pretreated CLM from 125 patients...
August 17, 2016: Molecular Cancer Therapeutics
N Lassau, B Coiffier, M Kind, V Vilgrain, J Lacroix, M Cuinet, S Taieb, R Aziza, A Sarran, C Labbe-Devilliers, B Gallix, O Lucidarme, Y Ptak, L Rocher, L M Caquot, S Chagnon, D Marion, A Luciani, S Feutray, J Uzan-Augui, B Benatsou, J Bonastre, S Koscielny
BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Xia Yin, Xiaojie Wang, Boqiang Shen, Ying Jing, Qing Li, Mei-Chun Cai, Zhuowei Gu, Qi Yang, Zhenfeng Zhang, Jin Liu, Hongxia Li, Wen Di, Guanglei Zhuang
We have previously reported surrogate biomarkers of VEGF pathway activities with the potential to provide predictive information for anti-VEGF therapies. The aim of this study was to systematically evaluate a new VEGF-dependent gene signature (VDGs) in relation to molecular subtypes of ovarian cancer and patient prognosis. Using microarray profiling and cross-species analysis, we identified 140-gene mouse VDGs and corresponding 139-gene human VDGs, which displayed enrichment of vasculature and basement membrane genes...
2016: Scientific Reports
Aurélie Bertaut, Caroline Truntzer, Rachid Madkouri, Coureche Guillaume Kaderbhai, Valentin Derangère, Julie Vincent, Bruno Chauffert, Marie Hélene Aubriot-Lorton, Wahlid Farah, Klaus Luc Mourier, Romain Boidot, Francois Ghiringhelli
Bevacizumab is used to treat glioblastoma; however, no current biomarker predicts its efficacy. We used an exploratory cohort of patients treated with the radiochemotherapy then bevacizumab or chemotherapy at recurrence (N = 265). Bevacizumab use increased median overall survival (OS) 18.7 vs 11.3 months, p = 0.0014). In multivariate analysis, age, initial surgery, neutrophil count, Karnofsky status >70% and bevacizumab administration were independent prognostic factors of survival. We found an interaction between bevacizumab use and baseline neutrophil count...
July 28, 2016: Oncotarget
Amalia Azzariti, Letizia Porcelli, Oronzo Brunetti, Marzia Del Re, Vito Longo, Patrizia Nardulli, Michele Signorile, Jian-Ming Xu, Angela Calabrese, Anna Elisa Quatrale, Evaristo Maiello, Vito Lorusso, Nicola Silvestris
AIM: To identify suitable biomarkers of response to bevacizumab (BV) - it remains an open question. The measurement of serum vascular endothelial growth factor (VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2 (Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatin-based chemotherapy...
July 21, 2016: World Journal of Gastroenterology: WJG
Giuseppe Di Lorenzo, Sabino De Placido, Martina Pagliuca, Matteo Ferro, Giuseppe Lucarelli, Sabrina Rossetti, Davide Bosso, Livio Puglia, Piero Pignataro, Ilaria Ascione, Ottavio De Cobelli, Michele Caraglia, Michele Aieta, Daniela Terracciano, Gaetano Facchini, Carlo Buonerba, Guru Sonpavde
INTRODUCTION: While the majority of the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors currently used for the therapy of metastatic renal cell carcinoma (mRCC) are small molecule agents inhibiting multiple targets, monoclonal antibodies are inhibitors of specific targets, which may decrease off-target effects while preserving on-target activity. A few monoclonal antibodies have already been approved for mRCC (bevacizumab, nivolumab), while many others may play an important role in the therapeutic scenario of mRCC...
July 27, 2016: Expert Opinion on Biological Therapy
Al B Benson, Igor Kiss, John Bridgewater, Ferry A L M Eskens, Carolyn Sasse, Sandra Vossen, Jihong Chen, Chip Van Sant, Howard A Ball, Anne Keating, Andrew Krivoshik
PURPOSE: Tivozanib, a selective inhibitor of VEGFR-1, -2, and -3, plus mFOLFOX6 in an advanced gastrointestinal cancer phase Ib study had encouraging antineoplastic activity and a tolerable safety profile. This randomized, open-label, phase II trial of tivozanib/mFOLFOX6 versus bevacizumab/mFOLFOX6 in patients with previously untreated metastatic colorectal cancer (mCRC) evaluated tivozanib activity versus bevacizumab. EXPERIMENTAL DESIGN: Treatment-naïve patients received mFOLFOX6 every 2 weeks of each 28-day cycle plus either tivozanib orally 1...
July 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
D Daniels, D Guez, D Last, C Hoffmann, D Nass, A Talianski, G Tsarfaty, S Salomon, A A Kanner, D T Blumenthal, F Bokstein, S Harnof, D Yekutieli, S Zamir, Z R Cohen, L Zach, Y Mardor
BACKGROUND AND PURPOSE: The interpretation of the radiologic response of bevacizumab-treated patients with recurrent high-grade gliomas represents a unique challenge. Delayed-contrast MR imaging was recently introduced for calculating treatment-response-assessment maps in patients with brain tumors, providing clear separation between active tumor and treatment effects. We studied the application of standard and delayed-contrast MR imaging for assessing and predicting the response to bevacizumab...
July 7, 2016: AJNR. American Journal of Neuroradiology
Benjamin F Chu, Gregory A Otterson
Although molecular targeted agents have improved the treatment of lung cancer, their use has largely been restricted to limited subsets of the overall population that carry specific mutations. Angiogenesis, the formation of new blood vessels from existing networks, is an attractive, more general process for the development of targeted anticancer therapies, because it is critical for the growth of solid tumors, including non-small-cell lung cancer. Growing tissues require a vascular supply within a few millimeters...
June 8, 2016: Clinical Lung Cancer
Cong Zhou, Andrew Clamp, Alison Backen, Carlo Berzuini, Andrew Renehan, Rosamonde E Banks, Richard Kaplan, Stefan J Scherer, Gunnar B Kristensen, Eric Pujade-Lauraine, Caroline Dive, Gordon C Jayson
BACKGROUND: There is a critical need for predictive/resistance biomarkers for VEGF inhibitors to optimise their use. METHODS: Blood samples were collected during and following treatment and, where appropriate, upon progression from ovarian cancer patients in ICON7, a randomised phase III trial of carboplatin and paclitaxel with or without bevacizumab. Plasma concentrations of 15 circulating angio-biomarkers were measured using a validated multiplex ELISA, analysed through a novel network analysis and their relevance to the PFS then determined...
July 12, 2016: British Journal of Cancer
Laurent Greillier, Pascale Tomasini, Fabrice Barlesi
Angiogenesis is one of the hallmarks of cancer. Antivascular endothelial growth factor therapy, including bevacizumab, is therefore a major option in targeting angiogenesis, especially for the management of stage IV nonsquamous non-small cell lung cancer patients. This review focuses first on the data from clinical trials available to date regarding efficacy and safety of chemotherapy plus bevacizumab. This review then highlights the current remaining questions related to the use of this drug in daily practice and how the patients might be clinically and radiologically selected...
October 2016: Therapeutic Advances in Respiratory Disease
Michael Pohl, Wolff Schmiegel
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer type in Western countries. Significant progress has been made in the last decade in the therapy of metastatic CRC (mCRC) with a median overall survival (OS) of patients exceeding 30 months. The integration of biologic targeted therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MABs) in the treatment of patients with genomically selected all-RAS wild-type mCRC leads to a significant progress in advanced incurable disease state...
2016: Digestive Diseases
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