Phase II study of bevacizumab in combination with cetuximab plus irinotecan in irinotecan-refractory colorectal cancer (CRC) patients who have progressed on a bevacizumab-containing regimen (The BOND 2.5 Study)

Abstract

4087 Background: We previously showed that adding bevacizumab (bev) to cetuximab (cetux) plus irinotecan (IRI) in bev-naïve, IRI-refractory CRC patients is feasible, and yielded a favorable response rate and time to tumor progression (TTP) compared with historical controls (Saltz: JCO, 2007). Since most CRC patients now receive a bev-containing regimen prior to cetux, we evaluated the addition of bev to cetux plus IRI (CBI) in patients with metastatic CRC who had previously progressed on chemo + bev. Methods: All patients were naïve to cetux. The importance of KRAS mutation was not appreciated when the trial was designed and this has not yet been evaluated. Patients received IRI at the same dose and schedule as last received prior to study, Cetux 400 mg/m2 loading dose, then weekly at 250 mg/m2, plus Bev 5 mg/kg given every two weeks or 7.5 mg/kg given every three weeks. Results: 33 received treatment. Median age was 58 (range 29–85). Median number of prior regimens was 2 (range 1–2). Median performance status was ECOG 1 (range 0–1). Patients received a median of 2 cycles (range 1–15). Grade 3/4 Toxicities: Acneiform Rash 18%, hypomagnesemia 6%, hypophosphatemia 6%, Neutropenia 15%, Diarrhea 6%. One patient developed neutropenic fever and one patient had a hypersensitivity reaction to cetux. At a median follow up of 32 months (range 21–32 months) in 33 evaluable patients, we observed 3 (9%) partial responses and 11 (33%) patients with stable disease for > 4 months. Median TTP was 3.9 months (95% CI: 1.3 - 6.8). Median survival was 10.6 months (95% CI: 6.6 - 13.8). Conclusions: The toxicity profile was similar to what would have been expected from the individual agents alone. Recognizing the limitations of cross-study comparisons, the response rates and TTP seen with CBI in patients who have previously progressed on bev do not appear to be as encouraging as the 37% response rate and 7.3 months TTP seen in the BOND 2 trial of bev-naïve CRC patients. Ongoing randomized trials, including SWOG 0600, will be needed to definitively determine the contribution of continued use of bev after progression on a bev-containing regimen. Supported by Genentech. [Table: see text]