Efficacy and safety assessment of the addition of bevacizumab to adjuvant therapy agents in cancer patients: A systematic review and meta-analysis of randomized controlled trials
Ahmadizar, Fariba; Onland-Moret, N. Charlotte; De Boer, Anthonius; Liu, Geoffrey; Maitland-Van Der Zee, Anke H.
(2015) PLoS One, volume 10, issue 9
(Article)
Abstract
Aim: To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients. Methods & Design/Results: PubMed, EMBASE, Cochrane and Clinical trials.gov databases were searched for English language studies of randomized controlled trials comparing bevacizumab and adjuvant therapy with adjuvant therapy alone published
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from January 1966 to 7thof May 2014. Progression free survival, overall survival, overall response rate, safety and quality of life were analyzed using random- or fixed-effects models according to the PRISMA guidelines. We obtained data from 44 randomized controlled trials (30,828 patients). Combining bevacizumab with different adjuvant therapies resulted in significant improvement of progression free survival (log hazard ratio, 0.87; 95% confidence interval (CI), 0.84-0.89), overall survival (log hazard ratio, 0.96; 95% CI, 0.94-0.98) and overall response rate (relative risk, 1.46; 95% CI: 1.33-1.59) compared to adjuvant therapy alone in all studied tumor types. In subgroup analyses, there were no interactions of bevacizumab with baseline characteristics on progression free survival and overall survival, while overall response rate was influenced by tumor type and bevacizumab dose (p-value: 0.02). Although bevacizumab use resulted in additional expected adverse drug reactions except anemia and fatigue, it was not associated with a significant decline in quality of life. There was a trend towards a higher risk of several side effects in patients treated by high-dose bevacizumab compared to the lowdose e.g. all grade proteinuria (9.24; 95% CI: 6.60-12.94 vs. 2.64; 95% CI: 1.29-5.40). Conclusions: Combining bevacizumab with different adjuvant therapies provides a survival benefit across all major subsets of patients, including by tumor type, type of adjuvant therapy, and duration and dose of bevacizumab therapy. Though bevacizumab was associated with increased risks of some adverse drug reactions such as hypertension and bleeding, anemia and fatigue were improved by the addition of bevacizumab.
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Keywords: alpha interferon, alpha2a interferon, anthracycline derivative, bevacizumab, capecitabine, capecitabine plus oxaliplatin, carboplatin, cetuximab, cisplatin, cyclophosphamide, docetaxel, doxorubicin, epirubicin, erlotinib, etoposide, fluorouracil, folinic acid, gemcitabine, irinotecan, oxaliplatin, paclitaxel, pemetrexed, placebo, prednisone, rituximab, taxane derivative, topotecan, trastuzumab, abdominal abscess, adult, anemia, arterial thromboembolism, bleeding, cancer adjuvant therapy, cancer patient, cardiotoxicity, congestive heart failure, controlled study, diarrhea, digestive system perforation, double blind procedure, drug dose comparison, drug efficacy, drug megadose, drug safety, dyspnea, epistaxis, fatigue, febrile neutropenia, female, heart left ventricle failure, high risk patient, human, hypertension, leukopenia, low drug dose, lung embolism, lung hemorrhage, major clinical study, male, meta analysis, middle aged, nausea, neutropenia, overall survival, phase 2 clinical trial, phase 3 clinical trial, pneumonia, practice guideline, progression free survival, proteinuria, quality of life, randomized controlled trial, rash, review, risk factor, solid tumor, stomatitis, survival rate, systematic review, thrombocytopenia, treatment duration, treatment response, venous thromboembolism, vomiting, wound healing impairment
ISSN: 1932-6203
Publisher: Public Library of Science
(Peer reviewed)
