BASEL, Switzerland, December 14 /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.
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
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