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.
OBJECTIVE
To evaluate the efficacy and safety of bevacizumab in the adjuvant cancer therapy setting within different subset of patients.
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 from January 1966 to 7th of 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 low-dose 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.
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands.
Fariba
F
Ahmadizar
Julius Center for Health Sciences and Primary Care, UMC Utrecht, the Netherlands.
N Charlotte
NC
Onland-Moret
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands.
Anthonius
A
de Boer
Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Hospital/University Health Network and University of Toronto, Toronto, Ontario, Canada; Division of Epidemiology, Dalla Lana School of Public Health, Toronto, Ontario, Canada.
Geoffrey
G
Liu
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, the Netherlands.
Anke H
AH
Maitland-van der Zee
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab