Randomized phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer

Abstract

3508 Background: Cetuximab (Cetux), a monoclonal antibody (mab) that targets the epidermal growth factor receptor (EGFR), has shown antitumor activity both alone and in combination with irinotecan (IRI) in IRI-refractory colorectal cancer (CRC). Bevacizumab (Bev), a mab against vascular endothelial growth factor (VEGF), improved the response rate, PFS, and overall survival in CRC patients treated with first line IFL. We evaluated the safety and efficacy of concurrent administration of these two monoclonal antibodies in patients with metastatic CRC. Methods: This is a randomized phase II study in patients with IRI-refractory CRC. All patients were naive to both bev and cetux. EGFR expression was not required for study entry. Arm A received IRI at the same dose and schedule as last received prior to study, plus Cetux 400 mg/m2 loading dose, then weekly at 250 mg/m2, plus Bev 5 mg/kg given every other week. Arm B received the same Cetux and Bev as arm A, but without IRI. Results: 76 patients have been randomized, 75 of whom received treatment. Median age is 60 (range 25–86). Median number of prior regimens is 3 (range 1–7). Median performance status is ECOG 1 (0–1). Interim toxicity data have been previously presented (ASCO GI Symposium, 1/05). No toxicities were encountered that would not have been expected from the single agents alone. As of 12/04, the median time to tumor progression (TTP) for arm A (Cetux/Bev/IRI) is 5.8 months, with 16 patients currently on treatment. For Arm B (Cetux/Bev) the median TTP was 4.0 months. Response data are shown in the table. Conclusions: The combination of Cetux/Bev, alone or with IRI, is tolerable. The response rates and TTP seen with the addition of Bev to either Cetux or Cetux/IRI appear favorable compared to historical controls of Cetux or Cetux/IRI without Bev. Studies of Cetux/Bev in conjunction with front line combination chemotherapy regimens are warranted and have now been initiated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Access, Genentech, Pfizer, Roche, Sanofi, Taiho Bristol-Meyers Squibb