New Phase III Data Highlights Excellent Efficacy of Roche's Cancer Drugs Xeloda and Avastin for Treatment of Advanced Colorectal Cancer

New Phase III Data Highlights Excellent Efficacy of Roche's Cancer Drugs Xeloda and Avastin for Treatment of Advanced Colorectal Cancer

January 22, 2007

    BASEL, Switzerland, Jan. 22 /Xinhua-PRNewswire/ -- New
Phase III data presented at the American Society of
Clinical Oncology Gastrointestinal Symposium (ASCO GI)
continue to demonstrate the excellent efficacy of two of
Roche's innovative cancer drugs Xeloda and Avastin, which
offer improved survival for patients with advanced
colorectal cancer. The NO16966 study showed that:

    -- XELOX (oral Xeloda plus oxaliplatin) is at least as
effective as 
       FOLFOX-4 in terms of overall survival

    -- The addition of Avastin to either XELOX or FOLFOX
leads to a 
       statistically significant improvement in
progression-free survival, as
       determined by an independent review committee (IRC)

    "Overall, these results confirm the role of XELOX
as the most convenient and patient-friendly treatment
option in this disease area, which is very encouraging for
colorectal cancer patients and healthcare providers,"
said Professor Jim Cassidy, co-lead investigator for study
NO16966 and Cancer Research UK Professor of Oncology and
Chair of Medical Oncology, Beatson Oncology Centre, at the
University of Glasgow, Scotland. "In addition, the
independent review confirms that by adding Avastin to any
oxaliplatin-based regimen we can improve progression-free
survival times even further, which we knew all along based
on the second-line data with FOLFOX plus Avastin."

    In the treatment of advanced (metastatic) colorectal
cancer, these data showed that XELOX reached its primary
endpoint:

    -- The chemotherapy combination XELOX is as effective
in terms of time
       patients live without their disease progressing
(PFS) as FOLFOX-4.

    -- Overall survival data of the first 634 patients
enrolled prior to the
       introduction of Avastin indicate that XELOX is at
least comparable to
       FOLFOX-4.

    These data add to the results of previous studies,
further endorsing that Xeloda should replace infused
5-FU/leucovorin in colorectal cancer regimens.

    The IRC which conducted a blinded analysis of the scans
confirmed that Avastin reached its primary endpoint:

    -- The benefit provided by Avastin when added to
chemotherapy 
       (FOLFOX or XELOX) significantly improved
progression-free 
       survival by 43% compared to chemotherapy alone, as
assessed 
       by the IRC. A previous analysis presented in October
2006 showed 
       an advantage of 20%.

    -- Specifically there was also a statistically
significant 
       improvement in PFS when assessing the addition of
Avastin to 
       either the XELOX or FOLFOX subgroup (p<0.007)

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

    Further analyses are ongoing and updated results will
be presented at future scientific meetings. Based on
findings from this study and the NO16967 and E3200 studies,
Roche will be approaching worldwide regulatory authorities
for new file submissions with Xeloda and Avastin
respectively in advanced colorectal cancer.

    In 2004, colorectal cancer was one of the leading
cancers and accounted for 13 percent of all cancers in
Europe.(1) A World Health Organization report suggested
that in 2005, 655,000 people worldwide died from colorectal
cancer.(2)

    Notes to Editors:

    About the Study

    NO16966

    NO16966 is a large, international Phase III trial which
finally recruited 2,034 patients. It was originally planned
to compare XELOX vs FOLFOX as first-line treatment in
metastatic colorectal cancer:

    -- XELOX (Xeloda plus oxaliplatin) vs FOLFOX-4
(intravenous bolus and
       infusional 5-fluorouracil plus oxaliplatin)

    The two-arm study recruited 634 patients.

    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 presented previously at the European Society of
Medical Oncology (ESMO) meeting in October 2006 of the
entire study population (N=2,034) show that:

    -- XELOX is as effective as FOLFOX in terms of PFS
(hazard 
       ratio: 1.05; upper limit of the 97.5 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:

    -- 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 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 early 2005 and in
the US in February 2004 for first-line treatment of
patients with advanced colorectal cancer. It received
another approval in the US in June 2006 as a second-line
treatment for patients with advanced colorectal cancer. The
first filing for Avastin in Japan occurred in April 2006 for
the treatment of advanced colorectal cancer.  Most recently
following priority review, the world's first angiogenesis
inhibitor was approved by the FDA in October for the
treatment of non-small cell lung cancer (NSCLC); a filing
for the same indication was submitted to EU authorities 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
iepost-operation). The total development programme is
expected to include over 40,000 patients worldwide.

    For more information, please visit
http://www.avastin-info.com 

    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.

    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 (
http://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:
      
http://www.roche.com/pages/downloads/company/pdf/mboncology05e_a.pdf

    -- Roche: http://www.roche.com 
    -- Broadcast quality B-roll including doctor, caregiver
and patient   
       interviews is available for download via
http://www.thenewsmarket.com 

    References:

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

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


    For more information, please contact:

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

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


SOURCE  Roche