Risk and management of venous thromboembolisms in bevacizumab-treated metastatic colorectal cancer patients.
OBJECTIVE
Bevacizumab may potentiate the risk of venous thromboembolisms (VTEs) in cancer patients, who are already predisposed to pro-thrombotic states. We aimed to characterize the incidence of VTEs in a population-based cohort of metastatic colorectal cancer (mCRC) patients treated with bevacizumab, describe patient and treatment factors associated with VTEs, and examine how VTEs are managed.


METHODS
Patients diagnosed with mCRC from 2006 to 2009 and offered bevacizumab were included. Descriptive statistics were used to describe VTE occurrences and management. Univariate and multivariate regression models were constructed to explore associations between clinical factors and VTEs.


RESULTS
We identified 541 mCRC patients: 27 never started bevacizumab and 15 were lost to follow-up. Of the 499 evaluable patients, median age was 61, 59.3% were men, 88.1% had ECOG 0/1, and 5.2% reported previous VTEs. Mean number of bevacizumab doses was 13.3 cycles. After receiving bevacizumab, 81 patients developed 93 cases of VTEs, with 9 patients experiencing >1 event. Individuals who experienced VTEs were more likely to have had pre-existing cardiovascular disease (OR 2.259, p = 0.0245), resection of primary cancer (OR 3.262, p = 0.0269), pre-chemotherapy platelet count ≥350,000/μL (OR 2.295, p = 0.0293), and received >12 bevacizumab cycles (OR 2.172, p = 0.0158). Use of bevacizumab varied after occurrence of VTE where it was discontinued in 34.4%, continued in 34.4%, and temporarily held in 1.1%.


CONCLUSIONS
VTE risk can be high, especially in patients with specific pre-treatment risk factors as well as in those who received more bevacizumab, suggesting a potential dose-related effect. Management of bevacizumab-related VTEs was variable.
Faculty of Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Irene
I
Yu
Division of Medical Oncology, British Columbia Cancer Agency, 600 West 10th Avenue, 4th Floor, Vancouver, BC, V5Z 4E6, Canada.
Leo
L
Chen
Division of Medical Oncology, British Columbia Cancer Agency, 600 West 10th Avenue, 4th Floor, Vancouver, BC, V5Z 4E6, Canada.
Jenny Y
JY
Ruan
Division of Medical Oncology, British Columbia Cancer Agency, 600 West 10th Avenue, 4th Floor, Vancouver, BC, V5Z 4E6, Canada.
Jennifer T
JT
Chang
Division of Medical Oncology, British Columbia Cancer Agency, 600 West 10th Avenue, 4th Floor, Vancouver, BC, V5Z 4E6, Canada. wcheung@bccancer.bc.ca.
Winson Y
WY
Cheung
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000068258:Bevacizumab / Q000009:adverse effects* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology* / Q000628:therapy; D020246:Venous Thrombosis / Q000453:epidemiology; D055815:Young Adult
D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab
Bevacizumab; Colorectal cancer; Metastasis; Venous thromboembolisms