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Basel, 2 October 2006

Avastin and Xeloda set new standards for the treatment of first-line metastatic colorectal cancer

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

Istanbul, Turkey, 2 October 2006, 17.00 CET – 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

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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).

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Further Information
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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