Hoffmann-La Roche Inc. Release: New Overall Survival Study Results Confirm Oral Xeloda(R) plus Oxaliplatin (XELOX) is Comparable to FOLFOX-4 for the First-Line Treatment of Advanced Colorectal Cancer

Growing Body of Data Supports XELOX as Effective Alternative to Standard of Care

NUTLEY, N.J., Jan. 16 /PRNewswire/ -- Overall survival results from a 14-month follow-up of the international, Phase III NO16966 study confirm that oral Xeloda(R) plus oxaliplatin (XELOX) is comparable to a current standard treatment, FOLFOX-4 (infused 5-FU/leucovorin plus oxaliplatin) in the first-line treatment of advanced (metastatic) colorectal cancer.

In the study, patients receiving XELOX lived for a median of 19.0 months, while patients receiving FOLFOX-4 lived for a median of 18.5 months. The consistency of these results were also further demonstrated in a subset population from the original two-arm part of the study (XELOX v. FOLFOX). These data will be presented on Sat., Jan. 17 at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco, Calif.

"These compelling data validate previous studies showing that XELOX is comparable to FOLFOX-4 for the treatment of advanced colorectal cancer, while providing the added flexibility of the proven oral component Xeloda," said Edward Chu, M.D., chief of medical oncology, Yale Cancer Center. "Together, these studies confirm the value and importance of combination therapy with oral Xeloda for the thousands of patients with this insidious disease, which is the second-leading cause of cancer deaths in the United States."

Colorectal cancer is the third most common cancer in the United States. The American Cancer Society estimated that in 2008 more than 148,000 people in the U.S. would be diagnosed and about 50,000 people would die from the disease.(1)

Previous data reported from the NO16966 study showed that XELOX is comparable to FOLFOX-4 in terms of progression-free survival, and the addition of Avastin to chemotherapy (FOLFOX-4 and XELOX) significantly improved progression-free survival by investigator assessment compared to chemotherapy alone. Furthermore, results from a separate international, Phase III study (NO16967) of 627 previously-treated patients with advanced colorectal cancer showed that XELOX is comparable to FOLFOX-4 in delaying disease progression.

"We're excited to see the continued promise of Xeloda as a cornerstone of combination cancer treatments," said Lars Birgerson, M.D., Ph.D., Vice President, Global Head, Medical Affairs, Roche. "With these overall survival data in advanced colorectal cancer, we have strong evidence that XELOX may offer an important new option for a difficult-to-treat patient population."

The ASCO GI meeting also will feature five additional Roche U.S. Xeloda abstracts, including a second XELOX abstract. These studies will be presented on Fri., Jan. 16 and Sat., Jan. 17. All other Xeloda abstracts are ex-U.S. or non-Roche sponsored studies.

About the Study

Study NO16966 is a large, randomized, international, Phase III trial of 2,034 advanced colorectal cancer patients that initially compared first-line XELOX (Xeloda + oxaliplatin) versus FOLFOX-4 (intravenous bolus and infusional 5-fluorouracil + oxaliplatin). After release of Avastin data in colorectal cancer in 2003, the protocol was amended to investigate, using a two by factorial design, XELOX + placebo versus XELOX + Avastin (7.5 mg/kg q3w) versus FOLFOX-4 + placebo versus FOLFOX-4 + Avastin (5.0 mg/kg q2w). The two-arm study recruited 634 patients; after transition to the two by factorial design, an additional 1,400 patients were recruited.

The primary protocol objectives were to answer: 1) whether the XELOX regimen was comparable to FOLFOX-4 in terms of clinical efficacy and 2) whether the addition of Avastin to chemotherapy improved results compared to chemotherapy alone. The secondary endpoints included overall survival, overall response rates, time to, and duration of, response and safety profile.

Both study arms had acceptable and similar safety profiles, with no unexpected toxicities. There was a lower incidence of grade 3/4 adverse events (AEs) and hematologic AEs in the pooled XELOX group compared to the FOLFOX-4 group. Grade 3/4 gastrointestinal disorders and hand-foot syndrome were more common with XELOX compared to FOLFOX-4.

Results regarding overall survival in addition to progression-free survival were previously presented at ASCO GI in 2007. These 14-month follow-up data result from the overall survival analysis and include all patients involved in the trial (pooled XELOX-containing arms vs. pooled FOLFOX-4-containing arms).

About XELOX

XELOX is an abbreviation for a type of combination chemotherapy used to treat colorectal cancer; it contains Xeloda (capecitabine) plus oxaliplatin.

About XELODA (capecitabine)

Xeloda is the only FDA-approved oral chemotherapy for both metastatic breast cancer and adjuvant and metastatic colorectal cancer. Inactive in pill form, Xeloda is enzymatically activated within the body; when it comes into contact with a naturally occurring protein called thymidine phosphorylase, or TP, Xeloda is transformed into 5-FU, a cytotoxic (cell-killing) drug. Because many cancers have higher levels of TP than does normal tissue, more 5-FU is delivered to the tumor than to other tissue.

A clinically important drug interaction between Xeloda and warfarin has been demonstrated; altered coagulation parameters and/or bleeding and death have been reported. Clinically significant increases in prothrombin time (PT) and INR have been observed within days to months after starting Xeloda, and infrequently within one month of stopping Xeloda. For patients receiving both drugs concomitantly, frequent monitoring of INR or PT is recommended. Age greater than 60 and a diagnosis of cancer independently predispose patients to an increased risk of coagulopathy.

Xeloda is contraindicated in patients who have a known hypersensitivity to 5-fluorouracil, and in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. Xeloda is contraindicated in patients with severe renal impairment. For patients with moderate renal impairment, dose reduction is required.

The most common adverse events (greater than or equal to 20%) of Xeloda monotherapy were diarrhea, nausea, stomatitis and hand-foot syndrome. As with any cancer therapy, there is a risk of side effects, and these are usually manageable and reversible with dose modification or interruption.

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. For additional information about the U.S. pharmaceuticals business, visit our website http://www.rocheusa.com. Product and treatment information for U.S. healthcare professionals is available at www.RocheExchange.com.

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(1) Cancer Facts & Figures 2008. American Cancer Society. Atlanta, GA, 2008. 5-6, 12.

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