Abdullah K Alahmari1, Ziyad S Almalki1, Ahmed K Alahmari2, Jeff J Guo3. 1. Graduate student, University of Cincinnati, College of Pharmacy, OH. 2. Student, King Khalid University, College of Medicine, Abha, Kingdom of Saudi Arabia. 3. Professor, Pharmacoepidemiology & Pharmacoeconomics, College of Pharmacy, University of Cincinnati Academic Health Center, OH.
Abstract
BACKGROUND: Bevacizumab is a recombinant, humanized monoclonal antibody that hinders the proliferation of new blood vessels required for malignant progression. The drug is considered safe and tolerable; however, some controversy remains about whether it is linked to venous and arterial thromboembolic events (TEEs). OBJECTIVE: To evaluate the risk for overall, venous, and arterial TEEs in patients with colorectal cancer (CRC) who are administered bevacizumab plus chemotherapy in randomized controlled trials (RCTs). METHODS: We searched PubMed and CENTRAL databases to extract reports of relevant trials that were published in English between January 1, 2003, and December 31, 2014. All RCTs in which bevacizumab plus chemotherapy was compared with standard chemotherapy or with placebo plus chemotherapy for the treatment of CRC, and TEEs were reported, were included in a meta-analysis. Risk ratios (RRs) with 95% confidence intervals (CIs) of TEEs were calculated for each RCT. Because the between-study heterogeneities (I2) were insignificant, a fixed-effect model was used to determine the effect size of each TEE. A funnel plot was created to assess publication bias, and 2 forms of sensitivity analyses were performed for each outcome. RESULTS: This meta-analysis included 22 RCTs with a total of 13,185 patients. Overall, compared with the control groups, patients with CRC who received bevacizumab were at significant risk for overall TEEs (RR, 1.334; 95% CI, 1.191-1.494; P <.001; I2 = 1.37%). Regarding venous TEEs, a significant risk was observed for patients who received bevacizumab versus control patients (RR, 1.244; 95% CI, 1.091-1.415; P = .001; I2 = 0.0%). Similarly, the risk for arterial TEEs was significant in bevacizumab-treated patients (RR, 1.627; 95% CI, 1.162-2.279; P = .005; I2 = 0.0%). Sensitivity analyses did not affect the level of significance of the effect size for each outcome, and no significant publication bias was observed. CONCLUSION: In all the studies reviewed in this meta-analysis, the risk for venous or arterial TEEs was associated with bevacizumab use in patients with CRC. Healthcare providers are encouraged to consider thromboprophylaxis agents, periodically monitor their patients who receive bevacizumab, and carefully manage patients who are at increased risk for those complications.
BACKGROUND:Bevacizumab is a recombinant, humanized monoclonal antibody that hinders the proliferation of new blood vessels required for malignant progression. The drug is considered safe and tolerable; however, some controversy remains about whether it is linked to venous and arterial thromboembolic events (TEEs). OBJECTIVE: To evaluate the risk for overall, venous, and arterial TEEs in patients with colorectal cancer (CRC) who are administered bevacizumab plus chemotherapy in randomized controlled trials (RCTs). METHODS: We searched PubMed and CENTRAL databases to extract reports of relevant trials that were published in English between January 1, 2003, and December 31, 2014. All RCTs in which bevacizumab plus chemotherapy was compared with standard chemotherapy or with placebo plus chemotherapy for the treatment of CRC, and TEEs were reported, were included in a meta-analysis. Risk ratios (RRs) with 95% confidence intervals (CIs) of TEEs were calculated for each RCT. Because the between-study heterogeneities (I2) were insignificant, a fixed-effect model was used to determine the effect size of each TEE. A funnel plot was created to assess publication bias, and 2 forms of sensitivity analyses were performed for each outcome. RESULTS: This meta-analysis included 22 RCTs with a total of 13,185 patients. Overall, compared with the control groups, patients with CRC who received bevacizumab were at significant risk for overall TEEs (RR, 1.334; 95% CI, 1.191-1.494; P <.001; I2 = 1.37%). Regarding venous TEEs, a significant risk was observed for patients who received bevacizumab versus control patients (RR, 1.244; 95% CI, 1.091-1.415; P = .001; I2 = 0.0%). Similarly, the risk for arterial TEEs was significant in bevacizumab-treated patients (RR, 1.627; 95% CI, 1.162-2.279; P = .005; I2 = 0.0%). Sensitivity analyses did not affect the level of significance of the effect size for each outcome, and no significant publication bias was observed. CONCLUSION: In all the studies reviewed in this meta-analysis, the risk for venous or arterial TEEs was associated with bevacizumab use in patients with CRC. Healthcare providers are encouraged to consider thromboprophylaxis agents, periodically monitor their patients who receive bevacizumab, and carefully manage patients who are at increased risk for those complications.
Authors: N C Tebbutt; F Murphy; D Zannino; K Wilson; M M Cummins; E Abdi; A H Strickland; R M Lowenthal; G Marx; C Karapetis; J Shannon; D Goldstein; S S Nayagam; R Blum; L Chantrill; R J Simes; T J Price Journal: Ann Oncol Date: 2011-01-27 Impact factor: 32.976
Authors: Aimery de Gramont; Eric Van Cutsem; Hans-Joachim Schmoll; Josep Tabernero; Stephen Clarke; Malcolm J Moore; David Cunningham; Thomas H Cartwright; J Randolph Hecht; Fernando Rivera; Seock-Ah Im; György Bodoky; Ramon Salazar; Frédérique Maindrault-Goebel; Einat Shacham-Shmueli; Emilio Bajetta; Martina Makrutzki; Aijing Shang; Thierry André; Paulo M Hoff Journal: Lancet Oncol Date: 2012-11-16 Impact factor: 41.316
Authors: Gary H Lyman; Kari Bohlke; Alok A Khorana; Nicole M Kuderer; Agnes Y Lee; Juan Ignacio Arcelus; Edward P Balaban; Jeffrey M Clarke; Christopher R Flowers; Charles W Francis; Leigh E Gates; Ajay K Kakkar; Nigel S Key; Mark N Levine; Howard A Liebman; Margaret A Tempero; Sandra L Wong; Mark R Somerfield; Anna Falanga Journal: J Clin Oncol Date: 2015-01-20 Impact factor: 44.544
Authors: Herbert Hurwitz; Louis Fehrenbacher; William Novotny; Thomas Cartwright; John Hainsworth; William Heim; Jordan Berlin; Ari Baron; Susan Griffing; Eric Holmgren; Napoleone Ferrara; Gwen Fyfe; Beth Rogers; Robert Ross; Fairooz Kabbinavar Journal: N Engl J Med Date: 2004-06-03 Impact factor: 91.245
Authors: Sarah E Jones; Ruth E Barker; Claire M Nolan; Suhani Patel; Matthew Maddocks; William D C Man Journal: J Thorac Dis Date: 2018-05 Impact factor: 2.895
Authors: Marina T Van Leeuwen; Steven Luu; Howard Gurney; Martin R Brown; Sallie-Anne Pearson; Kate Webber; Lee Hunt; Soojung Hong; Geoffrey P Delaney; Claire M Vajdic Journal: JNCI Cancer Spectr Date: 2020-08-24
Authors: Letizia Procaccio; Vera Damuzzo; Francesca Di Sarra; Alberto Russi; Federica Todino; Vincenzo Dadduzio; Francesca Bergamo; Alessandra Anna Prete; Sara Lonardi; Hans Prenen; Angelo Claudio Palozzo; Fotios Loupakis Journal: Drug Saf Date: 2019-02 Impact factor: 5.228