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predictive biomarker bevacizumab

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https://www.readbyqxmd.com/read/28303751/vasoactive-peptides-associate-with-treatment-outcome-ofbevacizumab-containing-therapy-in-metastatic-colorectal-cancer
#1
Helga Hagman, Pär-Ola Bendahl, Olle Melander, Jan Sundberg, Anders Johnsson, Mattias Belting
BACKGROUND: Hypertension is a common early adverse event of anti-angiogenic treatment of cancer and may associate with treatment response. However, blood pressure measurement as a surrogate response biomarker has methodological limitations, and predictive biomarkers of angiogenesis inhibitors are lacking. In disease associated with hypertension, vasoactive peptides have been linked to cardiovascular pressure load. Here, we have explored potential associations between circulating levels of vasoactive peptides and tumor response during bevacizumab-containing treatment of colorectal cancer...
March 17, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28298545/homeobox-b9-mediates-resistance-to-anti-vegf-therapy-in-colorectal-cancer-patients
#2
Carmine Carbone, Geny Piro, Francesca Simionato, Francesca Ligorio, Chiara Cremolini, Fotios Loupakis, Greta Alì, Daniele Rossini, Valeria Merz, Raffaela Santoro, Camilla Zecchetto, Marco Zanotto, Federica Di Nicolantonio, Alberto Bardelli, Gabriella Fontanini, Giampaolo Tortora, Davide Melisi
PURPOSE: The identification of predictive biomarkers for antiangiogenic therapies remains an unmeet need. We hypothesized that the transcription factor Homeobox B9 (HOXB9) could be responsible for the tumor resistance to the anti-VEGF agent bevacizumab. EXPERIMENTAL DESIGN: HOXB9 expression and activation were measured in eight models of colorectal and pancreatic cancer with different resistance to bevacizumab. Serum levels of Angiopoietin-like Protein (Angptl)2, CXC receptor ligand (CXCL)1, interleukin(IL)8, and Transforming Growth Factor (TGF)β1 in tumor-bearing mice were measured by multiplex xMAP technology...
March 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28286925/cabozantinib-for-renal-cell-carcinoma-current-and-future-paradigms
#3
REVIEW
Ahmed Abdelaziz, Ulka Vaishampayan
Cabozantinib was approved by the FDA in April 2016 for the treatment of advanced renal cancer, pretreated with at least one prior antiangiogenic therapy. This is the first agent in the therapy of kidney cancer to show a statistically significant improvement in all three endpoints of clinical efficacy, response rate, progression free survival, and overall survival (OS), in a phase III randomized trial. The reporting of METEOR coincided with that of the Checkmate 025 study which randomized similarly eligible patients to receive nivolumab or everolimus 10 mg daily...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28286565/everolimus-in-the-management-of-metastatic-neuroendocrine-tumours
#4
REVIEW
David L Chan, Eva Segelov, Simron Singh
Neuroendocrine tumours are increasing in incidence and cause a variety of symptoms. The mammalian target of rapamycin (mTOR) pathway plays a key role in neuroendocrine tumour (NET) pathogenesis, leading to increased lipid synthesis, protein synthesis and cellular growth. Upregulation of this pathway is noted in both hereditary and sporadic NETs. This understanding has led to investigations of mTOR inhibitors as therapy for metastatic NETs. After promising preclinical findings, everolimus, an mTOR inhibitor, was trialled in the RADIANT-1-4 studies on patients with advanced, well differentiated NETs...
January 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28275117/randomized-phase-ii-trial-of-parsatuzumab-anti-egfl7-or-placebo-in-combination-with-folfox-and-bevacizumab-for-first-line-metastatic-colorectal-cancer
#5
Rocío García-Carbonero, Eric van Cutsem, Fernando Rivera, Jacek Jassem, Ira Gore, Niall Tebbutt, Fadi Braiteh, Guillem Argiles, Zev A Wainberg, Roel Funke, Maria Anderson, Bruce McCall, Mark Stroh, Eric Wakshull, Priti Hegde, Weilan Ye, Daniel Chen, Ilsung Chang, Ina Rhee, Herbert Hurwitz
LESSONS LEARNED: These negative phase II results for parsatuzumab highlight the challenges of developing an agent intended to enhance the efficacy of vascular endothelial growth factor inhibition without the benefit of validated pharmacodynamic biomarkers or strong predictive biomarker hypotheses.Any further clinical development of anti-EGFL7 is likely to require new mechanistic insights and biomarker development for antiangiogenic agents. BACKGROUND: EGFL7 (epidermal growth factor-like domain 7) is a tumor-enriched vascular extracellular matrix protein that supports endothelial cell survival...
March 8, 2017: Oncologist
https://www.readbyqxmd.com/read/28246006/efficacy-of-bevacizumab-therapy-in-recurrent-malignant-gliomas-in-relation-to-the-prior-recurrence-pattern-or-tumor-location
#6
Masahide Matsuda, Eiichi Ishikawa, Tetsuya Yamamoto, Hiroyoshi Akutsu, Shingo Takano, Akira Matsumura
Although promising preliminary results have been widely observed with bevacizumab for recurrent malignant gliomas, many unanswered questions remain to be resolved to achieve an optimal outcome. No predictive biomarkers of a survival benefit from bevacizumab have been established, and no consensus exists about the response or survival benefit regarding the prior recurrence pattern or tumor location. Here we retrospectively analyzed the clinical benefit from bevacizumab for recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location...
February 25, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28209746/a-phase-ii-randomized-trial-go27827-of-first-line-folfox-plus-bevacizumab-with-or-without-the-met-inhibitor-onartuzumab-in-patients-with-metastatic-colorectal-cancer
#7
Johanna C Bendell, Howard Hochster, Lowell L Hart, Irfan Firdaus, Joseph R Mace, Joshua J McFarlane, Mark Kozloff, Daniel Catenacci, Jessie J Hsu, Stephen P Hack, David S Shames, See-Chun Phan, Hartmut Koeppen, Allen L Cohn
BACKGROUND: Dysregulated hepatocyte growth factor/mesenchymal-epithelial transition (MET) signaling is associated with poor prognosis and resistance to vascular endothelial growth factor inhibition in metastatic colorectal cancer (mCRC). We report outcomes from a double-blind, multicenter phase II trial of the MET inhibitor onartuzumab in combination with mFOLFOX-6 and bevacizumab for mCRC (GO27827; NCT01418222). MATERIALS AND METHODS: Patients were randomized 1:1 to receive onartuzumab (10 mg/kg intravenously [IV]) or placebo plus mFOLFOX-6 and bevacizumab (5 mg/kg IV)...
February 16, 2017: Oncologist
https://www.readbyqxmd.com/read/28188101/antiangiogenic-therapy-in-advanced-non-small-cell-lung-cancer-a-meta-analysis-of-phase-iii-randomized-trials
#8
REVIEW
Jacques Raphael, Kelvin Chan, Safiya Karim, Robert Kerbel, Henry Lam, Keemo Delos Santos, Ronak Saluja, Sunil Verma
We conducted a meta-analysis to evaluate the efficacy of adding any antiangiogenic therapy (AT) to the standard of care in advanced non-small-cell lung cancer (NSCLC). The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials, and Embase were searched to identify eligible trials. We included all phase III randomized trials with any line and type of treatment, histology. and AT dose. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and pooled odds ratio (OR) for overall response rates (RR) were calculated...
January 12, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28162945/postoperative-adjuvant-systemic-therapy-in-completely-resected-non-small-cell-lung-cancer-a-systematic-review
#9
REVIEW
Penelope Bradbury, Duvaraga Sivajohanathan, Adrien Chan, Swati Kulkarni, Yee Ung, Peter M Ellis
The purpose of the present review was to determine whether the use of postoperative adjuvant systemic therapy in patients with completely resected non-small-cell lung cancer (NSCLC) improves survival. Cancer Care Ontario's Program in Evidence-Based Care reviewed the evidence to update previously published recommendations for patients with completely resected NSCLC. Relevant studies were identified from a systematic MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews search of studies published from 2010 to 2016...
July 12, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28129643/il-8-and-enos-polymorphisms-predict-bevacizumab-based-first-line-treatment-outcomes-in-ras-mutant-metastatic-colorectal-cancer-patients
#10
Mariantonietta Di Salvatore, Filippo Pietrantonio, Armando Orlandi, Marzia Del Re, Rosa Berenato, Ernesto Rossi, Marta Caporale, Donatella Guarino, Antonia Martinetti, Michele Basso, Roberta Mennitto, Concetta Santonocito, Alessia Mennitto, Giovanni Schinzari, Ilaria Bossi, Ettore Capoluongo, Romano Danesi, Filippo de Braud, Carlo Barone
BACKGROUND: Predictive biomarkers of efficacy and toxicity of bevacizumab have not yet been validated. This study assessed the influence of IL-8, eNOS and VEGF-A polymorphisms in RAS mutated metastatic colorectal cancer patients receiving bevacizumab-based chemotherapy. METHODS: 120 patients treated with first-line combination FOLFOX6 plus bevacizumab were included. A historical cohort of 112 RAS mutated colorectal cancer patients treated with FOLFOX6 alone served as control group...
January 25, 2017: Oncotarget
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
REVIEW
Razelle Kurzrock, David J Stewart
Following the approval of bevacizumab, an antibody targeting 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-1/2/3, platelet-derived growth factor receptor-α/β, fibroblast growth factor receptor-1/2/3 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
#17
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
#18
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
#19
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
#20
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
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