Incidence of serious bleeding events (sBE) in patients (pts) with metastatic colorectal cancer (mCRC) receiving bevacizumab (BV) as part of a first-line regimen: Results from the BRiTE observational cohort study (OCS)

Abstract

4104 Background: BV prolongs overall survival and progression-free survival when added to chemotherapy (CT) for 1st-line and 2nd-line treatment of pts with mCRC. Grade 3–4 BE occurred in previous controlled trials (RCTs) of BV at a rate of 3.1%-5%. Generalization of these findings is limited because pts on full dose anticoagulation (FDAC) or on doses of aspirin (ASA) > 325 mg/day were excluded from RCTs with BV. In the BRiTE OCS, the rate of serious grade 3–4 bleeding events (sBEs) was determined and the influence of underlying factors that may increase the risk of bleeding in general, including anticoagulation (AC) and antiplatelet (AP) therapies, was assessed. Methods: Pts and methods for BRiTE have been described (Kozloff, ASCO 2006; A3537). Data on sBE and use of AC (FDAC or therapeutic) or AP (including ASA) therapies were collected. Multiple logistic regression was used to identify factors significantly associated with occurrence of sBEs. Results: Of 1,953 mCRC pts treated with 1st-line BV/CT, there were 52 sBEs reported from 48 (2.5%) pts as at June 20, 2007 (median follow-up of 20.8 mo). The median time to a sBE from the first BV dose was 6 months (range, 0.1–31.7). The most common site of sBE was gastrointestinal/rectal (55.8%). Pts with primary tumor of the rectum had a higher rate of sBE than pts with primary tumor of the colon (4.0% vs 2.0%). The rate of sBE was 4.5% (17/382) in pts on chronic AP therapy, 6.0% (8/133) in pts on FDAC therapy, and 2.9% (9/309) in pts on prophylactic AC therapy. The sBE rate in pts not on AC or AP therapy was 2.2% (29/1,337). The incidence of sBE in pts on both AC and AP therapy was 7.2% (15/208). Conclusions: The overall rate of sBE was low in BRiTE and similar to previous reports of all Grade 3–4 BE in pivotal trials with BV, despite allowance of FDAC and chronic AP therapy in BRiTE. Rates of sBE were not different between pts on prophylactic AC and pts not on AC or AP tx. Rates of sBE were also low in pts on FDAC tx in BRiTE. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Inc. Genentech, Inc., Roche, sanofi-aventis Genentech, Inc. Genentech, Inc., Roche, sanofi-aventis