Bevacizumab (BV) plus 5-FU/leucovorin (FU/LV) for advanced colorectal cancer (CRC) that progressed after standard chemotherapies: An NCI Treatment Referral Center trial (TRC-0301)

Abstract

3515 Background: The addition of bevacizumab (BV, Avastin) to IFL for untreated metastatic CRC produces survival benefit (Hurwitz et al, ASCO 2003), but the role of BV in other CRC settings is not established. The purpose of this trial is to evaluate the combination of BV with FU/LV for patients who have exhausted standard therapeutic options. Methods: This is a single arm, multicenter trial conducted nationwide through TRC. The 1st stage was to obtain the RR in 100 evaluable pts; if efficacy is observed, the 2nd stage would open as an expanded access protocol. Main eligibility criteria: advanced CRC progressing after irinotecan- and oxaliplatin-based regimens, ECOG PS 0–2. Treatment plan: BV 5 mg/kg q 2 wks, plus bolus or infusional FU/LV, in 8-wk cycles. All pts are followed for RR, safety, PFS and OS. Results: Due to rapid accrual, many patients were already in the pipeline awaiting study entry by the time the 1st stage accrual target was met. As a result, 350 pts were enrolled in the 1st stage between 7/03 and 11/03: 57% male, 93% ECOG PS 0–1, median age 61 (26–92), 78% with liver and 65% with lung metastases. To date, the median time from enrollment is 8 wks (5–22 wks). Based on partial follow-up at 8 wks, 2 pts had PR (pending confirmation), 19 had SD, 42 had PD; 264 pts are too early to assess. 10 pts have died (8 due to PD, 1 from pneumonia, 1 unknown); 8 pts were off therapy due to adverse events, including G3–4 GI bleeding (3), venous thrombosis (1), G3 CNS bleeding (1), G4 cerebral ischemia (1) and G4 atrial fibrillation (1). The study is currently closed to accrual while data collection for the 1st stage continues. By May 2004, all 350 pts will have had ≥ 6.5 months of follow-up; data on RR, PFS, OS and safety profile will be presented. Conclusion: It is clear that patients are interested in novel therapeutics such as BV. This trial will provide important safety and efficacy information on the BV/FU/LV regimen for CRC patients in the 3rd line setting. This TRC experience may also assist in planning nationwide trials with new agents in the future when similar situations arise. (Sponsored by NCI, in collaboration with Genentech, Inc.) No significant financial relationships to disclose.