Xeloda(R) Plus Avastin(R) Combination Delays Disease Progression in Women with Advanced Breast Cancer

Results of the XCALIBr (Xeloda in Combination with Avastin as First-Line Treatment for HER2-Negative Metastatic Breast Cancer) trial showed that oral Xeloda(R) (capecitabine) in combination with Avastin(R) (bevacizumab) effectively delayed time to disease progression (TTP) in metastatic breast cancer patients with no prior history of treatment. Metastatic breast cancer -- or cancer that has spread from the breast to other parts of the body -- has a poor prognosis, with a five-year survival rate of 20 percent.

In the Phase II study, the Xeloda/Avastin combination delayed breast cancer progression by a median of 5.7 months overall. Women with advanced ER+ (estrogen receptor positive) breast cancer demonstrated an especially significant delay in disease progression, with a median delay of 8.9 months; in fact, ten ER+ patients currently remain on treatment in the trial as their disease has not progressed to date. These data were presented today at the 43rd American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL.

"These encouraging results show that oral Xeloda in combination with Avastin appears to be an active first-line treatment option for metastatic ER+ breast cancer," said clinical trial investigator, George Sledge, M.D., Professor of Medicine and Pathology, Indiana University Cancer Center. "There continues to be an urgent need for new strategies to improve clinical outcomes in advanced breast cancer patients. Any potential option that offers increased time to disease progression is an important development."

Breast cancer is the most common cancer among women, other than skin cancer. It is the second leading cause of cancer death in women, after lung cancer. According to the American Cancer Society (ACS), about 178,480 women in the United States will be found to have invasive breast cancer in 2007 and about 40,460 women will die from the disease this year. Currently, there are slightly more than 2 million women living in the United States who have been treated for breast cancer. According to the ACS, breast cancer death rates are going down; the decline may be the result of early detection and treatment.

"These results highlight the promise of Xeloda as a foundational chemotherapy in combination with biotargeted agents designed to increase clinical benefit in women with advanced breast cancer," said Lars Birgerson, M.D., PhD, Vice President, Global Head Medical Affairs, Roche. "Roche is committed to supporting trials such as XCALIBr that explore the expanded use of Xeloda."

About the Study

The primary objective of the multi-center, single arm, Phase II trial was to evaluate time to progression (TTP) in chemotherapy-naive metastatic breast cancer patients receiving first-line Xeloda/Avastin combination therapy. Secondary endpoints included overall survival, overall response rate, response duration, biomarkers, quality of life, time-to-failure and safety profile. Study participants were limited to female outpatients diagnosed with HER2- negative (human epidermal growth factor receptor 2-negative) metastatic breast cancer, or locally recurrent breast cancer, who are age 18 and older, not pregnant and have no prior history of treatment.

In the study, patients received first-line therapy with Xeloda 1000 mg/m2 twice a day for 14 days with seven days off in combination with Avastin 15mg/kg IV in three-week cycles until first progression or intolerance to treatment. Once progression was documented, patients were treated with second- line therapy of Avastin 10mg/kg IV every two weeks in combination with either weekly paclitaxel 80 mg/m2 or vinorelbine 25 mg/m2 on four-week cycles. Clinical investigators chose whether the patient received paclitaxel or vinorelbine.

The study met its primary endpoint (to increase TTP to greater than or equal to 5.6 months), showing a median TTP of 5.7 months in an analysis of 106 intent-to-treat patients. In ER+ patients, median time to progression was 8.9 months.

The combination regimen resulted in an overall response rate of 38% (54% complete response; 33% partial response), and 42% of patients had stable (non-progressed) disease following treatment. This analysis demonstrated that treatment with Xeloda plus Avastin was well tolerated in the majority of patients.

The most common grade 3 adverse events were hand-foot syndrome (13%), a skin condition that is commonly seen with fluoropyrimidine agents, and diarrhea (8%). The only grade 4 toxicity reported was pulmonary embolism (4%).

In the patients who died (24%), the cause of death was primarily non- treatment related (22 patients) with an additional two patients dying from treatment-related complications.

About Xeloda

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. An employer of choice, in 2006, Roche was named one of the Top 20 Employers (Science magazine), ranked the No. 1 Company to Sell For (Selling Power), and one of AARP's Top Companies for Older Workers, and in 2005, Roche was named one of Fortune magazine's Best Companies to Work For in America. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or http://www.roche.us.