January 23, 2007

Roche: XELOX Regimen May Offer Advantages Over FOLFOX-4

Preliminary results show the combination of Xeloda plus Eloxatin, known as XELOX, to be equivalent to standard FOLFOX-4 chemotherapy treatment in terms of overall survival in first-line metastatic colorectal cancer patients. Given its dosing convenience advantage, XELOX has the potential to be a first-line treatment, provided it can be demonstrated as cost-effective.

The 2,034 metastatic colorectal cancer patient study was originally designed to compare first-line XELOX (Roche/Chugai's Xeloda plus Sanofi-Aventis's Eloxatin) with the standard therapy FOLFOX-4 (5-fluorouracil, leucovorin plus Eloxatin). However, following positive data and regulatory approval for Genentech/Roche's Avastin in the treatment of advanced colorectal cancer; the original study protocol was amended.

Instead of comparing XELOX with FOLFOX-4, the new protocol uses a two by two factorial design to compare XELOX plus placebo versus XELOX plus Avastin (7.5 mg/kg every three weeks) versus FOLFOX-4 plus placebo versus FOLFOX-4 plus Avastin (5.0 mg/kg every two weeks).

Although further analysis continues and will be presented at an international meeting later in the year; overall survival results suggest that XELOX is equivalent to FOLFOX-4 in 634 patients who formed the original arm of the study. Furthermore, independent analysis of the amended protocol suggests that the addition of Avastin to XELOX or FOLFOX-4 significantly improves progression-free survival.

These findings, added to results from another international phase III study, will form the basis of Roche's supplemental New Drug Application for Xeloda in the treatment of first-line, metastatic colorectal cancer. Roche is expected to file Xeloda with the FDA by year-end 2007.

With over 460,000 patients expected by Datamonitor to be diagnosed with colorectal cancer in the seven major markets in 2007, these preliminary results will be welcome news to Roche. Xeloda's oral availability will prove advantageous in comparison with infused 5-fluorouracil, and the XELOX regimen will compete well with FOLFOX-4 as a result.

As Roche has amended this latest trial so that Avastin was administered every three weeks at 7.5mg/kg compared with the usual 5mg/kg every two weeks in order to be conveniently administered in line with Eloxatin's three-weekly administration, this could also aid market uptake of XELOX.

However, given that 5-fluorouracil is a relatively cheap and widely genericized drug, the XELOX regimen is likely to be carefully scrutinized by payers for cost-effectiveness before it establishes itself as the standard first-line treatment for metastatic colorectal cancer.