Investor Update
Basel, 31 May 2008
Second
phase III study of Avastin plus chemotherapy shows improved progression-free survival in women with
advanced HER2-negative breast cancer
Positive AVADO results support efficacy and
safety of Avastin in first-line metastatic breast cancer
Roche today
announced that Avastin® (bevacizumab), in combination with docetaxel chemotherapy, significantly increased
the time women with metastatic breast cancer receiving first-line therapy lived without their disease
advancing, as defined by the primary endpoint of progression-free survival (PFS). In this placebo-controlled
Phase III trial (AVADO), two dose levels of Avastin in combination with docetaxel chemotherapy showed
a statistically significant improvement in PFS compared to docetaxel chemotherapy alone, according to
an investigator-assessed analysis. No new safety signals for Avastin were observed in the study.
The
results were featured today during a press briefing at the 44th Annual Meeting of the American Society
of Clinical Oncology (ASCO) in Chicago.
“These results build upon previous
data and expand our understanding of Avastin’s efficacy and safety when combined with another commonly
used taxane chemotherapy,” said Dr. David Miles, principal investigator of the study. “Importantly,
this study supports that Avastin can be used with taxane-based chemotherapy to provide a meaningful
benefit for patients with advanced HER2-negative breast cancer.”
Avastin
combined with chemotherapy improved PFS by up to 64 percent (hazard ratio of 0.61; p=0.0001) in the
15 mg/kg treatment arm and by up to 45 percent (hazard ratio of 0.69; p=0.0035) in the 7.5 mg/kg treatment
arm, compared to chemotherapy alone. Up to two thirds of patients (63%) experienced major shrinkage
of their tumor, which is unprecedented (p=0.0001). After one year, 83 percent and 78 percent of patients
were alive in the 15mg/kg and 7.5 mg/kg Avastin treatment arms, compared to 73 percent of patients receiving
chemotherapy alone.
“The positive results of the AVADO study are encouraging
news for patients suffering from metastatic breast cancer and confirm Avastin’s benefits as a treatment
against this devastating disease” said William M. Burns, CEO Pharmaceuticals Division of Roche. “With
our Avastin development program – the biggest trial program in oncology ever – we will continue to develop
the best possible treatment approaches to increase survival and improve quality of life of cancer patients.”
This
second large phase III trial follows the recently published E2100 study. Results from E2100 formed the
basis of European Commission approval and FDA accelerated approval of Avastin in combination with the
widely used chemotherapy paclitaxel for the first-line treatment of metastatic (HER-2 negative) breast
cancer in March 2007 and February 2008 respectively. Study E2100 showed that the addition of Avastin
to paclitaxel doubled patients’ chance of being alive without disease progression compared to paclitaxel
alone.
Each year more than one million women are diagnosed with breast
cancer leading to over 400,000 deaths globally.
About the
AVADO study
AVADO was an international, multicenter, randomized, double-blind,
placebo-controlled clinical trial that enrolled 736 patients with locally recurrent or metastatic HER2-negative
breast cancer who had not received chemotherapy for their metastatic disease. Patients were randomized
to one of two doses of Avastin (15 mg/kg or 7.5 mg/kg) or placebo given every three weeks in combination
with docetaxel chemotherapy for a maximum of nine cycles. Patients discontinuing docetaxel for
toxicity or after nine cycles were to continue on Avastin only or placebo until disease progression.
The AVADO study was not designed to compare the two dose levels of Avastin.
In
the 15 mg/kg and 7.5 mg/kg Avastin treatment arms, the 64 percent and 45 percent improvements in PFS
observed can also be referred to as 39 percent and 31 percent reductions in the risk of cancer progression
or death. Median PFS was 8.8 months, 8.7 months and 8.0 months in the 15 mg/kg and 7.5 mg/kg Avastin
plus chemotherapy arms and the chemotherapy alone arm, respectively. Overall response rates were
63 percent (p=0.0001) and 55 percent (p=0.0295) in the 15 mg/kg and 7.5 mg/kg Avastin plus chemotherapy
arms, compared to 44 percent in the chemotherapy alone arm.
The study
protocol specified analyses for overall survival at the time of primary endpoint analysis and 24 months
after the last patient was enrolled. The final analysis for overall survival is expected in 2009.
Hazard ratios for the preliminary analysis of overall survival are 0.68 and 0.92 for the 15 mg/kg
and 7.5 mg/kg Avastin arms, respectively. These initial results for overall survival are based
on early information.
No new safety signals related to Avastin were observed.
Furthermore, Avastin did not have a major impact on the known toxicity profile of docetaxel.
About
Avastin
Avastin
directly inhibits vascular endothelial growth factor (VEGF), a key mediator of angiogenesis (the growth
of new blood vessels). Blocking tumor angiogenesis with Avastin starves the tumor of the blood supply
that is critical for its growth and spread throughout the body (metastasis). Because Avastin directly
blocks tumor angiogenesis, a process common to all types of tumor development, it has the potential
to deliver patient survival benefits in a variety of different cancer types. Roche is therefore pursuing
a comprehensive clinical trial program investigating the use of Avastin in over 20 tumor types and different
settings (advanced, post surgical). The total development program is expected to include over 40,000
patients world-wide and has already resulted in approvals in advanced colorectal, breast, lung, and
kidney cancer.
- February 2004 (US) and January 2005 (EU) – first-line treatment in patients with metastatic colorectal cancer (CRC)
- June 2006 (US) – second-line treatment in patients with metastatic CRC
- October 2006 (US) and August 2007 (EU) – first-line treatment in patients with advanced non-small cell lung cancer
- March 2007 (EU) – first-line treatment in patients with metastatic breast cancer (BC)
- April 2007 (Japan) – treatment in patients with recurrent or advanced CRC
- December 2007 (EU) – first-line treatment in patients with advanced renal cell cancer
- January 2008 (EU) – first and later-line treatment in patients with metastatic CRC in combination with any chemotherapy
- February 2008 (US) - first line treatment in patients with HER-2 negative metastatic BC
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. As the world’s biggest biotech company and an innovator of
products and services for the early detection, prevention, diagnosis and treatment of diseases, the
Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche
is the world leader in in-vitro diagnostics and drugs for cancer and transplantation, and is a market
leader in virology. It is also active in other major therapeutic areas such as autoimmune diseases,
inflammatory and metabolic disorders and diseases of the central nervous system. In 2007 sales by the
Pharmaceuticals Division totalled 36.8 billion Swiss francs, and the Diagnostics Division posted sales
of 9.3 billion francs. Roche has R&D agreements and strategic alliances with numerous partners,
including majority ownership interests in Genentech and Chugai, and invested over 8 billion Swiss francs
in R&D in 2007. Worldwide, the Group employs about 79,000 people. Additional information is available
on the Internet at www.roche.com.
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