TREE2 Study – Bevacizumab with oxaliplatin-based chemotherapy, first-line for metastatic colorectal cancer

Preliminary results of the TREE-2 trial were presented at ASCO GI in January 2005. This was a randomised phase II multicentre study comparing three oxaliplatin plus fluoropyrimidine (O/F) regimens, each in combination with bevacizumab (Avastin), as first-line treatment for metastatic colorectal cancer.

A total of 223 patients were randomized to either FOLFOX6 plus bevacizumab, bFOL (a bolus 5-FU/Oxaliplatin combination) plus bevacizumab, or XELOX (Xeloda 850 mg/m2 days 1-14, Oxaliplatin 130 mg/m2 d 1, q3w) plus bevacizumab. The primary endpoint of the study was overall incidence of grade 3/4 toxicities during the first 12 weeks of study therapy for each of the study regimens. Secondary endpoints included overall response rate, time to tumour progression, overall survival, and time to treatment failure. Only the primary end point and response rate data is presented at this time. In terms of the primary endpoint, XELOX + bevacizumab displayed the lowest overall incidence of grade 3/4 toxicities in the first 12 weeks compared to mFOLFOX+ bevacizumab, and b-FOL+ bevacizumab (54% vs 65% and 59% respectively). In addition, the XELOX + bevacizumab arm had significantly lower neutropenia than the other two arms (1% v. 34% and 12 % respectively; p<0.05). As would be expected, Hand foot syndrome was more common in the XELOX arm than in the other arms. (6% in first 12 weeks, and 8% overall incidence). The FOLFOX + bevacizumab arm appeared to show an improved response rate compared to the bFOL + bevacizumab arm (p=0.029). No significant difference in response rate was seen between the FOLFOX + bevacizumab (46.9%) and XELOX + bevacizumab (37.5%) arms. In conclusion, the study showed that the addition of bevacizumab to all regimens was well tolerated with no significant additive toxicities seen. Bolus 5FU plus bevacizumab (bFOL) appeared to result in a higher response rate than infusional 5FU plus bevacizumab (FOLFOX-B), however there was no significant difference between FOLFOX-B and XELOX-B. Additional efficacy data including Time to progression, Progression free survival, and Overall survival, will be presented at ASCO 2005.