Xeloda

Press Release: Results Show XELOX Provides Equivalent Overall Patient Survival Compared To FOLFOX

Maureen Martino — Mon, 22 Jan 2007 11:39:27 -0500

Roche Release: Results Show XELOX Provides Equivalent Overall Patient Survival Compared To FOLFOX In Advanced Colorectal Cancer

NUTLEY, N.J., Jan. 22 -- Overall survival results from an international, Phase III study (NO16966) suggest that XELOX (Xeloda(R) plus oxaliplatin) is an effective alternative to the current standard treatment, FOLFOX-4 (infused 5-FU/leucovorin plus oxaliplatin), for advanced (metastatic) colorectal cancer. In the study, XELOX -- a more convenient therapy including Roche's oral Xeloda -- provides equivalent patient survival compared to FOLFOX-4. These data were presented at the American Society of Clinical Oncology Gastrointestinal Symposium (ASCO GI) in Orlando, FL.

The Independent Review Committee (IRC) analysis also confirmed previous results indicating that the addition of Avastin to combination chemotherapy (XELOX or FOLFOX) significantly improved the chance of delaying the progression of the disease (progression-free survival, or PFS).

"These important survival results continue to affirm our initial hypothesis that XELOX is a viable, effective alternative to the current standard of care for advanced colorectal cancer," said Professor Jim Cassidy, co-lead investigator for the study and Cancer Research UK Professor of Oncology and Chair of Medical Oncology, Beatson Oncology Centre, at the University of Glasgow, Scotland. "These data underscore the tremendous promise of combinations using cornerstone therapies such as Xeloda, and the potential benefit of adding Avastin to achieve greater progression-free survival."

Additional analysis of these data is ongoing and will be presented at an upcoming international scientific meeting.

"Now, with evidence of overall survival in addition to progression-free survival, we can move closer to offering patients a convenient option of an oral component to their chemotherapy treatment," said Lars Birgerson, Vice President, Medical Affairs, Roche. "Based on these findings and results from international Phase III study (NO16967), Roche will submit a supplemental new drug application for XELOX (Xeloda plus oxaliplatin) in advanced colorectal cancer."

In 2004, colorectal cancer was one of the leading cancers and accounted for 13 percent 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 estimated in 2006 that more than 148,000 people in the U.S. would be diagnosed and about 55,000 people would die from the disease.

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 2 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 primary study objectives were to answer two questions: 1) whether the XELOX regimen is non-inferior to FOLFOX; 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.

The results presented at ASCO GI represent only the original arm of the study, which recruited 634 patients.

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, the Roche Group 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 2005, Roche was named one of Fortune magazine's Best Companies to Work For in America, one of the Top 20 Employers (Science magazine), ranked as the No. 3 Best Company to Work For in NJ (NJ Biz magazine), the No. 1 Company to sell For (Selling Power), and one of AARP's Top Companies for Older Workers. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or www.roche.us.

Roche
CONTACT: Ginny Valenze of Roche, Office: +1-973-562-2783,virginia.valenze@roche.com; or Daphne Hoytt of Manning Selvage & Lee,Office: +1-212-468-3558, or Cell: +1-917-406-2779, daphne.hoytt@mslpr.com

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Press Release: Xeloda Combination Meets Primary Endpoint in Phase III Study

Maureen Martino — Sun, 10 Dec 2006 11:36:50 -0500

Xeloda Combination Meets Primary Endpoint in International Phase III Advanced Colorectal Cancer Study

- XELOX (Xeloda plus oxaliplatin) Delays Disease Progression in Patients with Recurring Cancer -

NUTLEY, N.J., Dec. 11 -- Roche announced today that a large, international Phase III study (NO16967) of 627 previously treated patients with advanced colorectal cancer met its primary endpoint of progression-free survival. Study results showed that the chemotherapy combination XELOX (oral Xeloda plus oxaliplatin) is as effective in delaying disease progression as the chemotherapy combination FOLFOX-4 (infused 5-FU/leucovorin plus oxaliplatin).

"Our data complement the findings of the NO16966 study, suggesting that XELOX is a very reasonable treatment option for patients with recurrent colorectal cancer," said Mace Rothenberg, MD, lead investigator and Professor of Medicine at Vanderbilt University Medical Center and Ingram Professor of Cancer Research at Vanderbilt-Ingram Cancer Center. "By demonstrating that Xeloda in combination with oxaliplatin was as effective as FOLFOX-4, these two studies provide the strongest evidence yet that Xeloda may be used in place of IV 5-FU in the treatment of patients with advanced colorectal cancer."

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 U.S. will be diagnosed and about 55,000 people will die from the disease.

"Roche is committed to advancing treatment for patients with colorectal cancer," said Lars E. Birgerson, Vice President, Medical Affairs, Roche. "Based on the data from the NO16966 and NO16967 studies, we are pleased to report that our filings with worldwide regulatory authorities will continue as planned."

Results from the NO16967 study will be submitted for presentation at future major medical meetings.

About the Study

The NO16967 trial is a large, international phase III trial that randomized 627 patients who had previously received chemotherapy and whose disease had returned or continued to progress. The trial compared XELOX (oral Xeloda plus oxaliplatin) vs. FOLFOX-4 (intravenous bolus and infusional 5-fluorouracil/leucovorin plus oxaliplatin) as first line colorectal cancer treatment. The primary objective was to determine whether the XELOX regimen was as effective as FOLFOX-4 in terms of progression-free survival (a measure of time to disease progression or death). The secondary outcomes included overall survival, overall response rates and safety profile. There were no unexpected safety findings in the study.

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)

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, the Roche Group 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 2005, Roche was named one of Fortune magazine's Best Companies to Work For in America, one of the Top 20 Employers (Science magazine), ranked as the No. 3 Best Company to Work For in NJ (NJ Biz magazine), the No. 1 Company to Sell For (Selling Power), and one of AARP's Top Companies for Older Workers. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or http://www.roche.us.

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Researchers renew enrolling cancer trial patients

Mon, 22 May 2006 20:01:36 -0400

Hoffman-LaRoche has renewed enrolling patients in a clinical trial of a combination of Xeloda and Avastin as a therapy for colon cancer. Enrollment had been suspended early this year after the sudden deaths of four patients involved in the study. But researchers say their independent safety review board said mortality rates were similar across all groups. They added a cardiac monitoring plan to detect any other deaths in the study that might occur.

- here's the AP report

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GSK halts cancer trial on positive data

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GlaxoSmithKline halted a late-stage clinical trial for its cancer therapy Tykerb after it exceeded its primary endpoint of time to disease progression. GSK will now move for regulatory approval for the drug in the second half of the year in Europe and the U.S. Researchers said that a combination therapy of Tykerb and capecitabine (Xeloda) versus capecitabine alone in women with advanced or metastatic breast cancer that have HER2 overexpression.

- read the AFX report

Safety concerns halt Avastin trial

Sun, 12 Feb 2006 19:01:39 -0500

Genentech and Roche Holdings, its majority owner, have suspended enrollment in a Phase III trial of Avastin for colon cancer after the deaths of four patients. Three of those four patients were younger people taking Avastin with Xeloda, which particularly troubled researchers. The news immediately hit shares of Roche in early trading. Researchers are exploring the utility of Avastin as an adjuvant therapy for post-surgical colon cancer. The Data Safety Monitoring Board believes that the rapid enrollment of 200 patients a month may have hindered proper safety evaluations.

Genentech said that it was right to temporarily halt enrollment so they could do a thorough analysis of safety data. Avastin is approved for colorectal cancer in patients whose disease has metastasized, an indication that should earn the companies $1.5 billion this year. Analysts doubted that the trial setback would create any significant long-term damage for either company's earnings.

- read this article from the Financial Times

Xeloda effective in prolonging survival of cancer patients

Tue, 01 Nov 2005 19:01:39 -0500

Roche said that a late-stage study of Xeloda with chemotherapy in advanced pancreatic cancer demonstrated its effectiveness in significantly prolonging the survival rate of patients. One-in-four patients taking Xeloda was still alive after a year compared to one-in-five who received chemotherapy alone. The data was reviewed at the European Cancer Conference in Paris.

"These data show there are new possibilities for pancreatic cancer patients who, in general, have a short life expectancy once diagnosed," said Julie Fleshman, JD, MBA, President and CEO of Pancreatic Cancer Action Network. "Because pancreatic cancer is one of the most aggressive forms of cancers, it is even more critical to discover and offer these patients more treatment options."

- read this AFX report for more information

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