{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:34:19Z","timestamp":1790436859672,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Ludwig Boltzmann Institute of Health Technology Assessment, Vienna, Austria"},{"name":"UMIT-University for Health Sciences"},{"name":"Medical Informatics and Technology, Hall i.T., Austria"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective.<\/jats:title>\n                  <jats:p>We performed a meta-analysis on adverse events seen with bevacizumab to combine the existing evidence about its safety in patients with advanced cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods.<\/jats:title>\n                  <jats:p>A systematic literature search was conducted to identify published, randomized controlled trials of bevacizumab in cancer patients with data on adverse events available. The primary endpoint was \u201csevere adverse event,\u201d a composite of grade 3 and 4 adverse events. Secondary endpoints for the exploratory analysis were individual adverse events. We used random-effects meta-analysis to combine data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results.<\/jats:title>\n                  <jats:p>Thirteen eligible publications were identified and eight trials reported the primary endpoint. Compared with the control group, the bevacizumab group had a slightly higher risk for any severe adverse event (pooled relative risk, 1.10; 95% confidence interval [95% CI], 1.01\u20131.19). The pooled risk difference was 7% (95% CI, 1%\u201313%), with a number needed to harm of 14 treated patients. Exploratory analyses showed a statistically significant higher risk for eight of the 15 evaluated secondary endpoints: bevacizumab was associated with a fourfold higher risk for hypertension, epistaxis, and gastrointestinal hemorrhage\/perforation; a threefold higher risk for any bleeding events; and a lower, but elevated risk for proteinuria, leukopenia, diarrhea, and asthenia. No statistically significant differences were found for any thrombotic event (arterial or venous), hemoptysis, cardiac event, thrombocytopenia, neutropenia, impaired wound healing, or death related to an adverse event.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion.<\/jats:title>\n                  <jats:p>Treatment with bevacizumab was associated with a slightly higher risk for any severe (grade 3 or 4) adverse event in patients with cancer. The result may impact individual benefit\u2013risk assessments and policy guidelines.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2009-0155","type":"journal-article","created":{"date-parts":[[2010,11,3]],"date-time":"2010-11-03T02:43:05Z","timestamp":1288752185000},"page":"1179-1191","source":"Crossref","is-referenced-by-count":57,"title":["Safety of Bevacizumab in Patients with Advanced Cancer: A Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.1093","volume":"15","author":[{"given":"Sabine","family":"Geiger-Gritsch","sequence":"first","affiliation":[{"name":"Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Information Systems and Health Technology Assessment, UMIT \u2013 University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria"},{"name":"Ludwig Boltzmann Institute of Health Technology Assessment, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjoern","family":"Stollenwerk","sequence":"additional","affiliation":[{"name":"Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Information Systems and Health Technology Assessment, UMIT \u2013 University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria"},{"name":"Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, Institute of Health Economics and Health Care Management, Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Miksad","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Institute for Technology Assessment and Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Guba","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Health Technology Assessment, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Wild","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Health Technology Assessment, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Siebert","sequence":"additional","affiliation":[{"name":"Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Information Systems and Health Technology Assessment, UMIT \u2013 University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria"},{"name":"Institute for Technology Assessment and Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Center for Health Decision Science, Department of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts, USA"},{"name":"Division of Public Health, Decision Modeling, Health Technology Assessment and Health Economics, ONCOTYROL Center for Personalized Cancer Medicine, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,11,2]]},"reference":[{"key":"2021122207515044200_R1","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1056\/NEJMoa032691","article-title":"Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer","volume":"350","author":"Hurwitz","year":"2004","journal-title":"N Engl J Med"},{"key":"2021122207515044200_R2","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1200\/JCO.2003.10.066","article-title":"Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)\/leucovorin (LV) with FU\/LV alone in patients with metastatic colorectal cancer","volume":"21","author":"Kabbinavar","year":"2003","journal-title":"J Clin Oncol"},{"key":"2021122207515044200_R3","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1200\/JCO.2005.05.112","article-title":"Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: Results of a randomized phase II trial","volume":"23","author":"Kabbinavar","year":"2005","journal-title":"J Clin Oncol"},{"key":"2021122207515044200_R4","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1056\/NEJMoa061884","article-title":"Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer","volume":"355","author":"Sandler","year":"2006","journal-title":"N Engl J Med"},{"key":"2021122207515044200_R5","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1056\/NEJMoa072113","article-title":"Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer","volume":"357","author":"Miller","year":"2007","journal-title":"N Engl J Med"},{"key":"2021122207515044200_R6","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1016\/S0140-6736(07)61904-7","article-title":"Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: A randomised, double-blind phase III trial","volume":"370","author":"Escudier","year":"2007","journal-title":"Lancet"},{"key":"2021122207515044200_R7","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ygyno.2006.01.030","article-title":"Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer","volume":"102","author":"Cohn","year":"2006","journal-title":"Gynecol Oncol"},{"issue":"28","key":"2021122207515044200_R8","doi-asserted-by":"crossref","first-page":"7135","DOI":"10.1200\/JCO.2005.16.139","article-title":"Phase II study of doxorubicin and bevacizumab for patients with metastatic soft-tissue sarcomas","volume":"23","author":"D'Adamo","year":"2005","journal-title":"Journal of Clinical Oncology Oct"},{"key":"2021122207515044200_R9","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1158\/1078-0432.CCR-03-0627","article-title":"Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: Therapy with sequential 1-beta-D-arabinofuranosylcytosine, mitoxantrone, and bevacizumab","volume":"10","author":"Karp","year":"2004","journal-title":"Clin Cancer Res"},{"key":"2021122207515044200_R10","doi-asserted-by":"crossref","first-page":"8033","DOI":"10.1200\/JCO.2005.01.9661","article-title":"Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer","volume":"23","author":"Kindler","year":"2005","journal-title":"J Clin Oncol"},{"key":"2021122207515044200_R11","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/cncr.21956","article-title":"Combination immunotherapy with prostatic acid phosphatase pulsed antigen-presenting cells (Provenge) plus bevacizumab in patients with serologic progression of prostate cancer after definitive local therapy","volume":"107","author":"Rini","year":"2006","journal-title":"Cancer"},{"key":"2021122207515044200_R12","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1245\/s10434-007-9389-5","article-title":"A randomized phase 2 trial of bevacizumab with or without daily low-dose interferon alfa-2b in metastatic malignant melanoma","volume":"14","author":"Varker","year":"2007","journal-title":"Ann Surg Oncol"},{"key":"2021122207515044200_R13","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1200\/JCO.2005.04.9130","article-title":"Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma","volume":"24","author":"Zhu","year":"2006","journal-title":"J Clin Oncol"},{"key":"2021122207515044200_R14","doi-asserted-by":"crossref","volume-title":"Common Terminology Criteria for Adverse Events","author":"National Cancer Institute","DOI":"10.32388\/ERJXIQ"},{"key":"2021122207515044200_R15","author":"Avastin\u00ae (Bevacizumab) - FDA Drug Label","year":"2008"},{"key":"2021122207515044200_R16","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1053\/j.ajkd.2006.11.039","article-title":"Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: Systematic review and meta-analysis","volume":"49","author":"Zhu","year":"2007","journal-title":"Am J Kidney Dis Feb"},{"key":"2021122207515044200_R17","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1093\/jnci\/djm086","article-title":"Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab","volume":"99","author":"Scappaticci","year":"2007","journal-title":"J Natl Cancer Inst"},{"key":"2021122207515044200_R18","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1001\/jama.2008.656","article-title":"Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: A meta-analysis","volume":"300","author":"Nalluri","year":"2008","journal-title":"JAMA"},{"key":"2021122207515044200_R19","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1016\/S0140-6736(99)04149-5","article-title":"Improving the quality of reports of meta-analyses of randomised controlled trials: The QUOROM statement. Quality of Reporting of Meta-analyses","volume":"354","author":"Moher","year":"1999","journal-title":"Lancet"},{"key":"2021122207515044200_R20","volume-title":"Avastin\u00ae (Bevacizumab) - Summary of Product Characteristics","author":"European Medicines Agency"},{"key":"2021122207515044200_R21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0197-2456(95)00134-4","article-title":"Assessing the quality of reports of randomized clinical trials: Is blinding necessary?","volume":"17","author":"Jadad","year":"1996","journal-title":"Control Clin Trials"},{"key":"2021122207515044200_R22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1017\/S0266462300008916","article-title":"Some statistical methods for combining experimental results","volume":"6","author":"Laird","year":"1990","journal-title":"Int J Technol Assess Health Care"},{"key":"2021122207515044200_R23","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"BMJ"},{"key":"2021122207515044200_R24","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions, Version 5.0.2 [updated September 2009] - The Cochrane Collaboration","author":"Higgins"},{"key":"2021122207515044200_R25","author":"Review Manager (RevMan) [Computer program]. Version 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration"},{"key":"2021122207515044200_R26","doi-asserted-by":"crossref","first-page":"3502","DOI":"10.1200\/JCO.2005.10.017","article-title":"Bevacizumab in combination with fluorouracil and leucovorin: An active regimen for first-line metastatic colorectal cancer","volume":"23","author":"Hurwitz","year":"2005","journal-title":"J Clin Oncol"},{"issue":"suppl 10","key":"2021122207515044200_R27","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1053\/j.seminoncol.2006.08.001","article-title":"Bevacizumab in the treatment of metastatic colorectal cancer: Safety profile and management of adverse events","volume":"33","author":"Hurwitz","year":"2006","journal-title":"Semin Oncol"},{"key":"2021122207515044200_R28","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2165\/00024669-200605010-00009","article-title":"Bevacizumab: A review of its use in advanced colorectal cancer, breast cancer, and NSCLC","volume":"5","author":"Lyseng-Williamson","year":"2006","journal-title":"Am J Cancer"},{"key":"2021122207515044200_R29","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1517\/14740338.5.4.553","article-title":"Incidence and management of bevacizumab-related toxicities in colorectal cancer","volume":"5","author":"Saif","year":"2006","journal-title":"Expert Opin Drug Saf"},{"key":"2021122207515044200_R30","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1093\/ajhp\/62.10.1021","article-title":"Bevacizumab in combination chemotherapy for colorectal and other cancers","volume":"62","author":"Motl","year":"2005","journal-title":"Am J Health Syst Pharm"},{"issue":"6","key":"2021122207515044200_R31","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1245\/s10434-006-9337-9","article-title":"Gastrointestinal perforation due to bevacizumab in colorectal cancer","volume":"14","author":"Saif","year":"2007","journal-title":"Ann Surg Oncol Jun"},{"key":"2021122207515044200_R32","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1200\/JCO.2005.00.232","article-title":"Combined analysis of efficacy: The addition of bevacizumab to fluorouracil\/leucovorin improves survival for patients with metastatic colorectal cancer","volume":"23","author":"Kabbinavar","year":"2005","journal-title":"J Clin Oncol"},{"key":"2021122207515044200_R33","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/jso.20301","article-title":"Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab","volume":"91","author":"Scappaticci","year":"2005","journal-title":"J Surg Oncol"},{"key":"2021122207515044200_R34","volume-title":"Avastin\u00ae (Bevacizumab) - European Public Assessment Report (EPAR)","author":"European Medicines Agency"},{"key":"2021122207515044200_R35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta11120","article-title":"Systematic review and economic evaluation of bevacizumab and cetuximab for the treatment of metastatic colorectal cancer","volume":"11","author":"Tappenden","year":"2007","journal-title":"Health Technol Assess"},{"key":"2021122207515044200_R36","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1200\/JCO.2006.07.8956","article-title":"European perspective on the costs and cost-effectiveness of cancer therapies","volume":"25","author":"Drummond","year":"2007","journal-title":"J Clin Oncol"},{"key":"2021122207515044200_R37","doi-asserted-by":"crossref","first-page":"3302","DOI":"10.1200\/JCO.2000.18.18.3302","article-title":"Systematic overview of cost-utility assessments in oncology","volume":"18","author":"Earle","year":"2000","journal-title":"J Clin Oncol"},{"key":"2021122207515044200_R38","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1023\/A:1008292128615","article-title":"Cost-effectiveness analysis in oncology","volume":"9","author":"Earle","year":"1998","journal-title":"Ann Oncol"},{"key":"2021122207515044200_R39","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s10198-003-0205-2","article-title":"When should decision-analytic modeling be used in the economic evaluation of health care [editorial]?","volume":"4","author":"Siebert","year":"2003","journal-title":"Eur J Health Econ"},{"key":"2021122207515044200_R40","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1056\/NEJMoa021491","article-title":"A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer","volume":"349","author":"Yang","year":"2003","journal-title":"N Engl J Med"},{"key":"2021122207515044200_R41","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1200\/JCO.2004.11.022","article-title":"Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer","volume":"22","author":"Johnson","year":"2004","journal-title":"J Clin Oncol"},{"key":"2021122207515044200_R42","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1200\/JCO.2005.05.098","article-title":"Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer","volume":"23","author":"Miller","year":"2005","journal-title":"J Clin Oncol"},{"key":"2021122207515044200_R43","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1200\/JCO.2006.09.6305","article-title":"Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the Eastern Cooperative Oncology Group Study E3200","volume":"25","author":"Giantonio","year":"2007","journal-title":"J Clin Oncol"},{"key":"2021122207515044200_R44","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1200\/JCO.2007.12.3026","article-title":"Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non small-cell lung cancer","volume":"25","author":"Herbst","year":"2007","journal-title":"J Clin Oncol"},{"key":"2021122207515044200_R45","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1200\/JCO.2007.14.9930","article-title":"Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study","volume":"26","author":"Saltz","year":"2008","journal-title":"J Clin Oncol"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1634\/theoncologist.2009-0155","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1634\/theoncologist.2009-0155","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/15\/11\/1179\/41843127\/oncolo_15_11_1179.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/15\/11\/1179\/41843127\/oncolo_15_11_1179.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T10:29:51Z","timestamp":1640168991000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/15\/11\/1179\/6399801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11,1]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2010,11,2]]},"published-print":{"date-parts":[[2010,11,1]]}},"URL":"https:\/\/doi.org\/10.1634\/theoncologist.2009-0155","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2010,11,1]]},"published":{"date-parts":[[2010,11,1]]}}}