Phase III XELOX Trial in Metastatic Colorectal Cancer Meets Primary Endpoints

Roche announced that a large, international phase III study (NO16966) enrolling 2,035 previously untreated metastatic colorectal cancer patients met both of its primary endpoints. Study results showed that:

• The chemotherapy combination of capecitabine (Xeloda) plus oxaliplatin (Eloxatin), known as XELOX, is as effective in terms of progression-free survival as infused fluorouracil (5-FU)/leucovorin plus oxaliplatin, known as FOLFOX.

• The addition of bevacizumab (Avastin) to chemotherapy (FOLFOX and XELOX) significantly improved progression-free survival compared to chemotherapy alone.

Some variability in subgroup analyses for efficacy was observed. No new safety signals related to bevacizumab were observed in the trial.

First Significant Comparative Data

"This is the first time we have significant data showing that oral Xeloda in combination with oxaliplatin is as effective as FOLFOX," said Lars E. Birgerson, vice president, medical affairs, Roche. "This study demonstrates that oral Xeloda plus oxaliplatin (XELOX) provides a new treatment option for colorectal patients. These data again show the benefits of adding Avastin to chemotherapy. In this trial, Avastin combined with XELOX and FOLFOX improved the chance of delaying progression of the disease by 20% in patients with advanced colorectal cancer. Furthermore, the results of this study underscore the tremendous potential of combinations using cornerstone therapies such as Xeloda."

In 2004, colorectal cancer was one of the leading cancers, accounting for 13% of all cancers; it is estimated that more than 394,000 people die worldwide from colorectal cancer each year. Colorectal cancer is the third most common cancer in the United States. The American Cancer Society estimates that in 2006, more than 148,000 people in the US will be diagnosed and about 55,000 people will die from the disease.

About the Study

The NO16966 trial was initially designed to compare XELOX vs FOLFOX as first line colorectal cancer treatment. After release of the pivotal bevacizumab data in colorectal cancer in 2003, the protocol was amended to investigate, in a 2X2 factorial design, XELOX plus placebo vs XELOX plus bevacizumab (7.5 mg/kg every 3 weeks) vs FOLFOX plus placebo vs FOLFOX plus bevacizumab (5.0 mg/kg every 2 weeks).

The primary objectives of the trial were to answer two questions: first, whether the XELOX regimen is noninferior to FOLFOX and, second, whether the addition of bevacizumab to chemotherapy is superior to chemotherapy alone. The secondary endpoints included overall survival, overall response rates, and safety profiles.