Investor Update
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
Results
from an international, phase III study presented for the first time today at the European Society for
Medical Oncology (ESMO) meeting in Istanbul, 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 (PFS) 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 1,3 4 5
“These
results
demonstrate for the first time that Avastin adds clinically meaningful and statistically significant
benefit in progression-free survival when combined with an oxaliplatin based chemotherapy in the 1st
line treatment of metastatic colorectal cancer. In addition, the data further endorses that oral Xeloda
should replace infused 5-FU/leucovorin in colorectal cancer regimens”, said Ed Holdener, Head of Roche
Pharma Development. “Based on these results, we plan to file a label extension for both Avastin and
Xeloda with worldwide regulatory authorities.”
“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
In
2004, colorectal cancer was one of the leading cancers and accounted for 13 percent of all cancers in
Europe
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 1,000 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 Xeloda
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
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.
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