gms | German Medical Science

Background: In a phase III pivotal trial in patients (pts) with metastatic colorectal cancer (mCRC), bevacizumab (BEV) increased overall survival by 30% when added to first-linechemotherapy (CT): IFL (Irinotecan, bolus-5-FU, Folinic acid). Safety data from controlled BEV trials have been described, and indicate that certain serious adverse events (SAE), primarily gastrointestinal (GI) perforations and arterial thromboembolic events (TE) occurred more often in pts who received CT with BEV than those who received CT alone. First BEAT was opened to evaluate safety events of BEV in a broader pt population using a variety of CT regimens mainly using infusional 5-FU or capecitabine instead of bolus-5-FU.

Methods: First BEAT started in June 2004 and aims to enrol up to 2000 mCRC pts. Eligible pts starting with first-line CT (physician’s choice) are treated until progression with BEV (5mg/kg q2w [5FU based CT] or 7.5mg/kg q3w [capecitabine based CT]). SAEs include deaths, new and prolonged hospitalizations, life-threatening as well as medically significant events. BEV-related (investigators’ assessment) SAE’s and survival are reported within 24 hours.

Results: By Fall 2005, 1605 pts had been enrolled in 35 countries. 1198 pts (male 58%; median age 60 years [30% were > 65 years]; PS 0-1 99%) had baseline data available for analyses. Median follow-up was 5.6 months (mean 5.8); 1078 pts had been followed-up for >60 days. The most common first-line CT regimens used with BEV were FOLFOX (27%), CAPOX (16%), FOLFIRI (23%) and capecitabine monotherapy (8%). Among the 1198 pts that had started treatment with BEV, 448 SAEs were reported in 289 pts (24%). 60-day mortality was 2.8%. The most common SAE were diarrhoea 3% and pyrexia 2.3% and were usually not attributed as related to BEV. Related SAEs were reported in 90 (8%) pts. Deep venous TE 1.5%, bleeding 1.3%, pulmonary embolism 1.0%, GI perforation 0.8%, arterial TE 0.8%, hypertension 0.5% were usually classified as related SAEs.Updated safety data (including additional SAEs) will be available in early 2006.

Conclusions: In this ongoing, large community-based study, the safety profile of BEV in first line mCRC pts receiving a variety of CT regimens popular in Europe, namely FOLFOX, CAPOX, FOLFIRI and capecitabine, appears consistent with that observed in large phase III randomised studies.