Avastin and Xeloda Set New Standards for the Treatment of First-Line Metastatic Colorectal Cancer

Avastin and Xeloda Set New Standards for the Treatment of First-Line Metastatic Colorectal Cancer

October 03, 2006

XELOX offers a new treatment option; the addition of Avastin to oxaliplatin-based chemotherapy demonstrates superior progression-free survival

    ISTANBUL, Turkey, Oct. 3 /Xinhua-PRNewswire/ -- Results
from an international, Phase III study presented for the
first time today at the European Society for Medical
Oncology (ESMO) meeting, show that two innovative cancer
drugs, Xeloda and Avastin, are set to provide new effective
treatment options for patients with advanced colorectal
cancer.

    The study showed that: 

    -- The chemotherapy combination XELOX (oral Xeloda plus
oxaliplatin) is as
       effective in terms of progression-free survival and
more convenient
       than the current standard treatment FOLFOX-4
(infused 5-FU/leucovorin
       plus oxaliplatin) in the treatment of advanced
(metastatic) colorectal
       cancer. 

    -- The addition of the anti-angiogenic agent Avastin to
chemotherapy
       (FOLFOX-4 and XELOX) significantly improves
progression-free survival
       compared to chemotherapy alone. 

    No new safety findings related to Avastin or Xeloda
were observed in the trial. Overall survival data are still
maturing.  Previous Avastin studies showed both a
progression-free and overall survival benefit for Avastin
when combined with chemotherapy regimens compared to
chemotherapy alone in the treatment of metastatic
colorectal cancer (1,2).

    These data further endorse that oral Xeloda should
replace infused 
5-FU/leucovorin in colorectal cancer regimens.

    "These results are very encouraging for doctors
and patients alike. They confirm that XELOX offers an
important new treatment option for metastatic colorectal
cancer -- one that is equally effective and more convenient
than the current standard treatment.  When compared to the
FOLFOX-4 regimen, patients on the XELOX combination have
significantly more free time from infusion treatment, only
2 hrs versus 48 hrs and fewer hospital/clinic visits,"
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.  "In addition, the
study confirms that by adding Avastin to chemotherapy we
can improve progression-free survival times even
further."

    Avastin added to chemotherapy resulted in a clinically
meaningful and statistically significant improvement of 20
percent in progression-free survival.  The duration of
therapy with Avastin was shorter than in previously
reported trials.  Early Avastin discontinuation, largely
unrelated to Avastin-specific toxicity occurred at a
three-fold higher rate in this study compared to previous
trials(1,3), which may have contributed to the outcome.
Further analyses are ongoing and results will be presented
at upcoming scientific meetings.

    In 2004, colorectal cancer was one of the leading
cancers and accounted for 13 percent of all cancers in
Europe.(4)  A World Health Organization report suggested
that, in 2005, 655,000 people worldwide died from
colorectal cancer.(5)

    NOTES TO EDITORS:

    -- PFS is a measure of the time patients live without
their disease
       progressing. 

    About the Study
    The NO16966 trial is a large, international, Phase III
trial which finally randomised 2,034 patients.  It was
originally planned to compare XELOX vs FOLFOX as first-line
colorectal cancer treatment including 1000 patients:

    -- XELOX (Xeloda plus oxaliplatin) vs FOLFOX
(intravenous bolus and
       infusional 5-fluorouracil plus oxaliplatin)

    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:

    -- XELOX + placebo vs XELOX + Avastin (7.5 mg/kg q3w)
vs. FOLFOX + placebo
       vs FOLFOX + Avastin (5.0 mg/kg q2w).

    The primary objective was 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. 

    Results to date show that:

    -- XELOX (Xeloda plus oxaliplatin) is as effective as
FOLFOX (infused 5-FU
       plus oxaliplatin) in terms of PFS (hazard ratio:
1.05; upper limit of
       the 95 percent confidence interval was below the
non-inferiority margin
       of 1.23).

    -- Adding Avastin to chemotherapy (FOLFOX and XELOX)
significantly
       improved PFS compared to chemotherapy alone (hazard
ratio: 0.83).  This
       means that adding Avastin to either chemotherapy
combination improves
       the chances of delaying progression of the disease
by 20 percent.

    -- No unexpected safety findings were identified for
either XELOX or
       Avastin in this study:

       -- Adverse events which occurred at a rate greater
than 10 percent in
          any of the treatment arms were: diarrhoea
(FOLFOX, 11.2 percent of
          patients; XELOX, 20.2 percent of patients),
neutropenia (FOLFOX,
          43.8 percent of patients, XELOX, 7.0 percent of
patients) and
          neurosensory toxicity (FOLFOX, 16.5 percent of
patients; XELOX, 17.4
          percent of patients).

       -- The percentage of gastrointestinal perforations
was 0.6 percent in
          the Avastin arms compared to 0.3 percent in the
placebo group. 
          Grade 3/4 arterial thromboembolic events occurred
in 1.7 percent vs
          1.0 percent respectively.  Grade 3/4 proteinuria
was reported for
          0.6 percent of all patients receiving Avastin. 
Wound healing
          complications were not observed in a higher
frequency than in the
          placebo group (0.1 vs 0.3 percent).

    About XELOX
    An abbreviation for a type of combination chemotherapy
used to treat colorectal cancer; it contains Xeloda
(capecitabine) plus oxaliplatin. 

    About Xeloda (capecitabine)
    Xeloda is licensed in more than 90 countries worldwide
including the EU, USA, Japan, Australia and Canada and has
been shown to be an effective, safe, simple and convenient
oral chemotherapy in treating over 1 million patients to
date.

    Roche received marketing authorisation for Xeloda as a
first-line monotherapy (by itself) in the treatment of
metastatic colorectal cancer (colorectal cancer that has
spread to other parts of the body) in most countries
(including the EU and USA) in 2001. Xeloda has also been
approved by the European Medicines Agency (EMEA) and U.S.
Food and Drug Administration (FDA) for adjuvant
(post-surgery) treatment of colon cancer in March and June
2005, respectively.

    Xeloda is licensed in combination with Taxotere
(docetaxel) in women with metastatic breast cancer (breast
cancer that has spread to other parts of the body) and
whose disease has progressed following intravenous (i.v.)
chemotherapy with anthracyclines. Xeloda monotherapy is
also indicated for treatment of patients with metastatic
breast cancer that is resistant to other chemotherapy drugs
such as paclitaxel and anthracyclines.  Xeloda recently
received approval in South Korea for the first-line
treatment of patients with locally advanced (metastatic)
pancreatic cancer, in combination with gemcitabine.  Xeloda
is licensed in South Korea for the first-line treatment of
stomach cancer.

    The most commonly reported adverse events with Xeloda
include diarrhoea, abdominal pain, nausea, stomatitis and
hand-foot syndrome (palmar-plantar erythrodysesthaesia).

    About Avastin (bevacizumab)
    Avastin is the first treatment that inhibits
angiogenesis -- the growth of a network of blood vessels
that supply nutrients and oxygen to cancerous tissues. 
Avastin targets a naturally occurring protein called
Vascular Endothelial Growth Factor (VEGF), a key mediator
of angiogenesis, thus choking off the blood supply that is
essential for the growth of the tumour and its spread
throughout the body (metastasis).

    In Europe, Avastin was approved in January 2005 and in
the US in February 2004 for the first-line treatment of
patients with metastatic colorectal cancer.  It received
another approval in the US in June 2006 as a second-line
treatment for patients with metastatic colorectal cancer. 
The first filing for Avastin in Japan occurred in April
2006 for the treatment of metastatic colorectal cancer. 
Following the filings with FDA in the US, Avastin was filed
with European Health Authorities in advanced breast cancer
in July and in metastatic non-small cell lung cancer
(NSCLC) in August. 

    Roche and Genentech are pursuing a comprehensive
clinical programme investigating the use of Avastin in
various tumour types (including colorectal, breast, lung,
pancreatic cancer, ovarian cancer, renal cell carcinoma and
others) and different settings (advanced and adjuvant i.e. 
post-operation).  The total development programme is
expected to include over 40,000 patients worldwide.

    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 a
supplier of innovative products and services for the early
detection, prevention, diagnosis and treatment of disease,
the Group contributes on a broad range of fronts to
improving people's health and quality of life.  Roche is a
world leader in diagnostics, the leading supplier of
medicines for cancer and transplantation and a market
leader in virology. In 2005, sales by the Pharmaceuticals
Division totalled 27.3 billion Swiss francs, and the
Diagnostics Division posted sales of 8.2 billion Swiss
francs.  Roche employs roughly 70,000 people in 150
countries and has R&D agreements and strategic
alliances with numerous partners, including majority
ownership interests in Genentech and Chugai. Additional
information about the Roche Group is available on the
Internet ( www.roche.com ).

    All trademarks used or mentioned in this release are
legally protected.

    Further Information Available from Media Relations
Contacts:

    -- Colorectal cancer fact sheet 
    -- Xeloda in colorectal cancer fact sheet 
    -- Avastin in colorectal cancer fact sheet
    -- Xeloda fact sheet
    -- Avastin fact sheet
    -- Roche in oncology:   
      
www.roche.com/pages/downloads/company/pdf/mboncology05e_a.pdf
    -- Roche: www.roche.com 
    -- Broadcast quality B-roll including doctor, caregiver
and patient
       interviews is available for download via
www.thenewsmarket.com 

    References:
    (1) Hurwitz H, Fehrenbacher L, Novotny W et al.
Addition of bevacizumab
        (rhuMab-VEGF) to bolus IFL in the first-line
treatment of patients
        with metastatic colorectal cancer: results of a
randomized Phase III
        trial. New England Journal of Medicine 2004;
350(23): 2335-2342

    (2) Giantonio BJ, Catalano PJ, Meropol NJ, et al.
High-dose bevacizumab
        improves survival when combined with FOLFOX4 in
previously treated
        advanced colorectal cancer: results from the
Eastern Cooperative
        Oncology Group (ECOG) study E3200. J Clin Oncol
2005; 23.

    (3) Kabbinavar FF, et al. J Clin Oncol 2005;23:3706-12

    (4) Boyle P, Ferlay J. Cancer incidence and mortality
in Europe, 2004.
        Annals of Oncology 2005;16:481-488

    (5) World Health Organization,
http://www.who.int/healthinfo/statistics/bodprojections2030/en/index.html

    CONTACT:  

    Roche
     Julia Pipe
     International Communications Manager - Xeloda
     Tel:   [phone]
     Email: [e-mail]

     Christine Mage-Hill
     Senior International Communications Manager, Avastin
     Tel:   [phone]
     Email: [e-mail]

    Shire Health International, New York
     Joanne Marlin
     Tel:   [phone]
     Email: [e-mail]

SOURCE  Roche