Avastin and Xeloda Receive Positive Recommendations for Label Extensions in Europe for Treatment of Advanced Colorectal Cancer

Basel, Switzerland (ots/PRNewswire) - Roche has received positive
recommendations for the Marketing Authorisation extensions for both
its anti-angiogenic agent Avastin (bevacizumab) and oral
chemotherapy Xeloda (capecitabine) from the European Committee for
Medicinal Products for Human Use (CHMP). The recommendation for the
extended label of Xeloda aims to broaden its use in combination with
other chemotherapies for the treatment of advanced colorectal cancer.
Similarly, the label extension for Avastin aims to broaden its use to
include Avastin with XELOX (Xeloda plus oxaliplatin) or FOLFOX-4
(5-FU/LV plus oxaliplatin) in patients with advanced colorectal
cancer (beyond the current label with 5-FU/LV and
5-FU/LV/irinotecan).

The positive recommendations are based on the results of three
large international Phase III pivotal studies (NO16966 and NO16967
for Xeloda and NO16966 and E3200 for Avastin).

Regarding Xeloda, studies NO16966 and NO16967 showed:

- XELOX to be at least as effective (non-inferior) - in terms
of both progression-free survival (PFS) and overall survival - as a
current standard treatment, FOLFOX-4 (intravenous bolus and infusional
5-FU/LV plus oxaliplatin) for both 1st and 2nd line treatment.

Regarding Avastin:
- The study NO16966 showed that:
- The addition of Avastin to chemotherapy (XELOX or FOLFOX-4)
significantly improved progression-free survival by 20% compared with
chemotherapy alone.
- In patients that received treatment until disease progression, the
benefit was even greater, and adding Avastin to chemotherapy improved
progression-free survival by 58%.
- The study E3200 showed that:
- The addition of Avastin to chemotherapy (FOLFOX-4) for patients having
relapsed disease improved overall survival by 33% compared to patients
who received FOLFOX-4 alone.

"The CHMP positive opinions are encouraging news for patients and
healthcare providers in the fight against colorectal cancer," said
Jean-Jacques Garaud, Head of Global Pharma Development at Roche. "We
look forward to receiving EU approvals, which will mark another
milestone in our commitment to developing effective and safe
treatments for the thousands of colorectal cancer patients throughout
the world."

No new safety findings related to Avastin or Xeloda were observed
in either trial.

These filings in Europe followed the submission of a supplemental
new drug application (sNDA) to the U.S. Food and Drug Administration
(FDA) in March for the use of XELOX (Xeloda in combination with
oxaliplatin) with or without Avastin (bevacizumab) in the treatment
of advanced colorectal cancer.

Details of the Studies

NO16966

NO16966 is a large, international Phase III trial which finally
recruited 2,034 patients. It was originally planned to compare XELOX
vs FOLFOX-4 as first-line treatment in advanced colorectal cancer.
After release of the pivotal Avastin data in colorectal cancer in
2003, the protocol was amended to investigate using a 2 by 2
factorial design: FOLFOX-4/XELOX + placebo vs FOLFOX-4/XELOX +
Avastin.

The primary objective was to answer two questions: 1) whether the
XELOX regimen is non-inferior to FOLFOX-4; 2) whether the addition of
Avastin to chemotherapy improved progression-free survival compared
to chemotherapy alone. The secondary endpoints included overall
survival, overall response rates, time to, and duration of, response
and safety profile.

Results of the study showed:
- The chemotherapy combination XELOX is as effective in terms of
progression-free survival- a measure of the time patients live without
their disease progressing - as FOLFOX-4;
- The addition of Avastin to chemotherapy (FOLFOX-4 and XELOX)
significantly improved progression-free survival compared to chemotherapy
alone.

NO16967

The NO16967 trial is a large, international phase III trial which
randomized 627 patients from 15 countries worldwide who had
previously received irinotecan-containing combination chemotherapy
and whose disease had returned or continued to progress. The primary
objective was to answer whether the XELOX regimen (Xeloda plus
oxaliplatin) is as effective as FOLFOX-4 (i.v. bolus and infusional
5-FU/LV plus oxaliplatin) in terms of progression-free survival. The
secondary outcomes to be reviewed included overall survival, overall
response rates, and safety profile. The results showed:

- The chemotherapy combination XELOX is as effective in terms of
progression-free survival as the chemotherapy combination FOLFOX-4.

E3200

The E3200 study is a randomized, controlled, multicenter Phase III
trial (E3200) of 829 patients with advanced or advanced CRC who had
received previous treatment with irinotecan and 5-FU as initial
therapy for advanced disease or as adjuvant therapy. The study showed
that patients who received Avastin plus the 5-FU-based chemotherapy
regimen known as FOLFOX-4 (oxaliplatin/5-FU/leucovorin) had a 25%
reduction in the risk of death (based on a hazard ratio of 0.75), the
primary endpoint, which is equivalent to a 33% improvement in overall
survival, compared to patients who received FOLFOX-4 alone. Median
survival for patients receiving Avastin plus FOLFOX-4 was 12.9
months, compared to 10.8 months for those receiving FOLFOX-4 alone.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's
leading research-focused healthcare groups in the fields of
pharmaceuticals and diagnostics. Additional information is available
on the Internet at http://www.roche.com.

ots Originaltext: Roche Pharmaceuticals
Im Internet recherchierbar: http://www.presseportal.de

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For further information please contact: Julia Pipe, International
Communications, Manager ¿Xeloda, F.Hoffmann-La Roche, Mob:
+41-79-263-9715, Email: julia.pipe@roche.com, Christine Mage-Hill,
Senior International Communications Manager, Avastin, F.Hoffmann-La
Roche, Mob: +41-79-788-8245, Email: christine.mage-hill@roche.com