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Predictive biomarkers bevacizumab

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https://www.readbyqxmd.com/read/28068936/retrospective-study-of-ras-pik3ca-braf-tumor-mutations-as-predictors-of-response-to-first-line-chemotherapy-with-bevacizumab-in-metastatic-colorectal-cancer-patients
#1
Izuma Nakayama, Eiji Shinozaki, Tomohiro Matsushima, Takeru Wakatsuki, Mariko Ogura, Takashi Ichimura, Masato Ozaka, Daisuke Takahari, Mitsukuni Suenaga, Keisho Chin, Nobuyuki Mizunuma, Kensei Yamaguchi
BACKGROUND: After analysis of minor RAS mutations (KRAS exon 3, 4/NRAS) in the FIRE-3 and PRIME studies, an expanded range of RAS mutations were established as a negative predictive marker for the efficacy of anti-EGFR antibody treatment. BRAF and PIK3CA mutations may be candidate biomarkers for anti-EGFR targeted therapies. However, it remains unknown whether RAS/PIK3CA/BRAF tumor mutations can predict the efficacy of bevacizumab in metastatic colorectal cancer. We assessed whether selection according to RAS/PIK3CA/BRAF mutational status could be beneficial for patients treated with bevacizumab as first-line treatment for metastatic colorectal cancer...
January 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28040423/prognostic-significance-of-increases-in-hemoglobin-in-renal-cell-carcinoma-patients-during-treatment-with-vegf-directed-therapy
#2
Abhishek Tripathi, Susanna Jacobus, Hope Feldman, Toni K Choueiri, Lauren C Harshman
BACKGROUND: Increases in hemoglobin have been reported in renal cell carcinoma (RCC) patients treated with vascular endothelial growth factor (VEGF) pathway-targeted therapies and have been associated with increased progression-free survival (PFS). We retrospectively evaluated its significance as a predictive biomarker of clinical response in RCC. PATIENTS AND METHODS: Patients with advanced RCC treated with VEGF receptor tyrosine kinase inhibitors (TKIs) or bevacizumab as a first-line therapy were identified...
December 13, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28025786/egfr-gene-amplification-and-kras-mutation-predict-response-to-combination-targeted-therapy-in-metastatic-colorectal-cancer
#3
Sajid A Khan, Zhaoshi Zeng, Jinru Shia, Philip B Paty
Genetic variability in KRAS and EGFR predicts response to cetuximab in irinotecan refractory colorectal cancer. Whether these markers or others remain predictive in combination biologic therapies including bevacizumab is unknown. We identified predictive biomarkers from patients with irinotecan refractory metastatic colorectal cancer treated with cetuximab plus bevacizumab. Patients who received cetuximab plus bevacizumab for irinotecan refractory colorectal cancer in either of two Phase II trials conducted were identified...
December 26, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28003187/angiopoietin-2-as-a-biomarker-and-target-for-immune-checkpoint-therapy
#4
Xinqi Wu, Anita Giobbie-Hurder, Xiaoyun Liao, Courtney Connelly, Erin M Connolly, Jingjing Li, Michael P Manos, Donald Lawrence, David McDermott, Mariano Severgnini, Jun Zhou, Evisa Gjini, Ana Lako, Mikel Lipschitz, Christine J Pak, Sara Abdelrahman, Scott Rodig, F Stephen Hodi
Immune checkpoint therapies targeting CTLA-4 and PD-1 have proven effective in cancer treatment. However, the identification of biomarkers for predicting clinical outcomes and mechanisms to overcome resistance remain as critical needs. Angiogenesis is increasingly appreciated as an immune modulator with potential for combinatorial use with checkpoint blockade. Angiopoietin-2 (ANGPT2) is an immune target in patients and is involved in resistance to anti-VEGF treatment with the monoclonal antibody bevacizumab...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27997006/-nivolumab-in-second-line-treatment-of-squamous-non-small-cell-lung-cancer
#5
Filippo De Marinis, Antonio Passaro
The treatment of non-small cell lung cancer (NSCLC) is changing dramatically in the last period, considering both non-squamous and squamous disease. In the last five years, the identification of different molecular predictive biomarker (e.g., EGFR, ALK e ROS1) and the utilize of new chemotherapy agents associated or not with antiangiogenics agents (e.g., bevacizumab and nintedanib), allowed the improvement of survival and related responses to these treatments. However, these advances, did not allow an improvement of the same endpoints in the management of NSCLC with squamous cell histology (SCC), where until very recently, docetaxel in monotherapy remained as a corner stone treatment for the second line, although associated with an unfavorable toxicity profile...
December 2016: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/27940520/exploring-the-benefit-risk-associated-with-antiangiogenic-agents-for-the-treatment-of-non-small-cell-lung-cancer-patients
#6
Razelle Kurzrock, David J Stewart
Following the approval of bevacizumab, an antibody targeting vascular endothelial growth factor-A (VEGF-A), for advanced non-squamous non-small cell lung cancer (NSCLC) in 2006, intensive efforts were put into the clinical development of antiangiogenic agents for NSCLC. Currently, the other antiangiogenic agents approved for NSCLC are ramucirumab, a VEGF receptor-2 (VEGFR-2)-targeting antibody indicated for both squamous and non-squamous NSCLC in the United States, and nintedanib, an anti-VEGFR-½/3, platelet-derived growth factor receptor (PDGFR)-α/β, fibroblast growth factor receptor (FGFR)-½/3 angiokinase inhibitor indicated for adenocarcinoma of the lung in the European Union...
December 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27868413/-progress-on-clinical-application-of-bevacizumab-for-the-treatment-of-refractory-cervical-cancer
#7
Bin He, Yanlan Chai, Tao Wang, Zhenxing Zhou, Zi Liu
Bevacizumab is increasingly used in recurrent, persistent or metastatic cervical cancer. The early retrospective case reports found that bevacizumab combined with 5-FU (including capecitabine) or paclitaxel was well tolerated and displayed encouraging anti-tumor activity in recurrent or persistent cervical cancer. Phase Ⅱ clinical trials showed that bevacizumab was well tolerated and active in the second- and third-line treatment of patients with recurrent cervical cancer. Large scale phase Ⅱ and phase Ⅲ clinical trials demonstrated that bevacizumab-containing chemotherapy was effective in the first- and second-line treatment of patients with persistent cervical cancer, prolonged survival time and improved remission rate...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/27843607/association-between-bevacizumab-related-hypertension-and-response-to-treatment-in-patients-with-metastatic-colorectal-cancer
#8
Isabel José Dionísio de Sousa, Joana Ferreira, Joana Rodrigues, Nuno Bonito, Paula Jacinto, Mariela Marques, João Ribeiro, Ana Pais, Helena Gervásio
BACKGROUND: Bevacizumab has become standard of care as first-line treatment of metastatic colorectal cancer (mCRC), after proving increased response rates and improvement in survival outcomes. Hypertension (HTN) is a common complication of the treatment with bevacizumab and, owing to its close relation with antiangiogenic mechanism, may represent a clinical biomarker to predict the efficacy of the treatment. The aim of this study was to retrospectively evaluate if HTN grades 2 to 3 were correlated with response to treatment with bevacizumab in first line, as well as with improved progression-free survival (PFS) and overall survival (OS), in a series of patients with mCRC...
2016: ESMO Open
https://www.readbyqxmd.com/read/27817944/bevacizumab-plus-paclitaxel-versus-placebo-plus-paclitaxel-as-first-line-therapy-for-her2-negative-metastatic-breast-cancer-meridian-a-double-blind-placebo-controlled-randomised-phase-iii-trial-with-prospective-biomarker-evaluation
#9
David Miles, David Cameron, Igor Bondarenko, Lyudmila Manzyuk, Juan Carlos Alcedo, Roberto Ivan Lopez, Seock-Ah Im, Jean-Luc Canon, Yaroslav Shparyk, Denise A Yardley, Norikazu Masuda, Jungsil Ro, Neelima Denduluri, Stanislas Hubeaux, Cheng Quah, Carlos Bais, Joyce O'Shaughnessy
AIM: MERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC). METHODS: In this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m(2) on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal...
January 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/27803067/large-scale-radiomic-profiling-of-recurrent-glioblastoma-identifies-an-imaging-predictor-for-stratifying-anti-angiogenic-treatment-response
#10
Philipp Kickingereder, Michael Götz, John Muschelli, Antje Wick, Ulf Neuberger, Russell T Shinohara, Martin Sill, Martha Nowosielski, Heinz-Peter Schlemmer, Alexander Radbruch, Wolfgang Wick, Martin Bendszus, Klaus H Maier-Hein, David Bonekamp
PURPOSE: Antiangiogenic treatment with bevacizumab, a mAb to the VEGF, is the single most widely used therapeutic agent for patients with recurrent glioblastoma. A major challenge is that there are currently no validated biomarkers that can predict treatment outcome. Here we analyze the potential of radiomics, an emerging field of research that aims to utilize the full potential of medical imaging. EXPERIMENTAL DESIGN: A total of 4,842 quantitative MRI features were automatically extracted and analyzed from the multiparametric tumor of 172 patients (allocated to a discovery and validation set with a 2:1 ratio) with recurrent glioblastoma prior to bevacizumab treatment...
December 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27782226/-the-evolution-of-the-treatment-of-advanced-nsclc
#11
Alessandro Morabito
The therapeutic scenario of patients with advanced non-small-cell lung cancer (NSCLC) has dramatically changed in recent years, thanks to the improvement in the knowledge of the biology of NSCLC, the discovery of targetable oncogenic drivers, and the availability of new effective drugs also for non oncogenic addicted patients, defined "wild-type" (WT). NSCLC has been the first epithelial neoplasm treated with a targeted first-line therapy in patients harbouring EGFR activating mutations or ALK rearrangements, and new targeted-based agents directed versus other molecular alterations are currently in development...
October 2016: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/27712015/randomized-study-of-folfiri-plus-either-panitumumab-or-bevacizumab-for-wild-type-kras-colorectal-cancer-wjog-6210g
#12
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...
December 2016: Cancer Science
https://www.readbyqxmd.com/read/27664394/improvement-in-survival-end-points-of-patients-with-metastatic-renal-cell-carcinoma-through-sequential-targeted-therapy
#13
REVIEW
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...
November 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27626306/assessment-of-bevacizumab-resistance-increased-by-expression-of-bcat1-in-idh1-wild-type-glioblastoma-application-of-dsc-perfusion-mr-imaging
#14
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
https://www.readbyqxmd.com/read/27621699/everolimus-in-the-management-of-metastatic-renal-cell-carcinoma-an-evidence-based-review-of-its-place-in-therapy
#15
REVIEW
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
https://www.readbyqxmd.com/read/27575850/a-functional-bioassay-to-determine-the-activity-of-anti-vegf-antibody-therapy-in-blood-of-patients-with-cancer
#16
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
https://www.readbyqxmd.com/read/27568331/blood-based-biomarkers-for-monitoring-antiangiogenic-therapy-in-non-small-cell-lung-cancer
#17
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
https://www.readbyqxmd.com/read/27557121/geometrical-measures-obtained-from-pretreatment-postcontrast-t1-weighted-mris-predict-survival-benefits-from-bevacizumab-in-glioblastoma-patients
#18
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
https://www.readbyqxmd.com/read/27551256/update-on-anti-angiogenesis-therapy-in-colorectal-cancer
#19
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
https://www.readbyqxmd.com/read/27535973/expression-of-genes-involved-in-vascular-morphogenesis-and-maturation-predicts-efficacy-of-bevacizumab-based-chemotherapy-in-patients-undergoing-liver-resection
#20
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
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