Investor Update

Basel, 11 March 2009

Herceptin proven to benefit women with HER2 positive early breast cancer – latest results from the HERA study

Study confirms Herceptin’s promise of extra years of living cancer free

The Breast International Group (BIG) in collaboration with Roche announced today that women with HER2 positive early breast cancer continue to benefit from Herceptin (trastuzumab) several years after treatment completion and as a result enjoy a longer life disease free. The patients were treated for one year with Herceptin and followed up for four years. These data from the HERA study were presented at the Primary Therapy in Early Breast Cancer conference in St. Gallen, Switzerland.

The HERA (HERceptin Adjuvant) study showed that women treated with Herceptin had a 25% reduction in the risk of their cancer coming back compared to women who did not receive Herceptin, and after four years of medical observation on average, almost 90% of the Herceptin-treated women were still alive. In addition to the significant treatment benefit, this analysis confirmed the long-term safety profile of Herceptin, with good cardiac safety and tolerability maintained throughout the four-year follow-up period.

“These data are extremely important for the treatment of breast cancer” commented Dr Martine Piccart, lead investigator of the HERA study and Chair of BIG. “HERA is the first of the four large Herceptin studies in early HER2 positive breast cancer to substantiate the long-term benefit derived from one year of treatment”.

“These important long-term results from the HERA trial reinforce that women with this aggressive type of cancer have the best chance of cure with Herceptin”, said William M. Burns, CEO of Roche’s Pharmaceuticals Division.

Historically, HER2 positive breast cancer has been associated with a poor prognosis, but the first analysis of the HERA trial, released in 2005, established unprecedented benefits in terms of lowering the risk of cancer returning (disease-free survival). “It is rewarding to see that women with HER- 2 positive early breast cancer can be confident about their future with Herceptin as the foundation of their treatment” said Dr Luca Gianni from the Istituto Nazionale Tumori Milano, Italy, lead investigator of the HERA study.

To date, four large studies – HERA, NSABP B-31, NCCTG N9831 and BCIRG 006 – have consistently demonstrated that Herceptin prolongs survival in women with HER2 positive early breast cancer.

About the HERA study

HERA is a large international phase III study conducted as collaboration between BIG and Roche. The study, with over 5000 patients enrolled, is assessing the benefits of adjuvant Herceptin treatment in women with HER2 positive early breast cancer. The primary endpoint is disease-free survival (DFS), the secondary endpoint is overall survival (OS) and cardiac safety.

Previously, with 2 years of median follow up, the HERA study demonstrated that one year of treatment with Herceptin given at three-weekly intervals after the completion of adjuvant chemotherapy and/or radiotherapy achieved a highly significant improvement in DFS versus the observation group (no Herceptin), reducing the relative risk of relapse by 36% (hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.54, 0.76; p=0.0001).1  Herceptin also reduced the risk of death by 34% compared to observation (HR: 0.66; 95% CI: 0.47, 0.91; p=0.0115). Upon publication of these unprecedented results in 2005, more than 50% of the patients in the observation arm opted to receive Herceptin (‘crossed-over’ to Herceptin treatment).  

The focus of the current analysis was to evaluate the efficacy and safety of one year of Herceptin treatment versus no Herceptin at a median of four years follow-up after entry onto the study. The results of the analysis including all women involved in the trial (intent to treat, ITT) showed a 25% reduction in risk of cancer recurrence for women receiving Herceptin compared to those on observation (no Herceptin) (HR 0.76; p=0.0001). At four years of follow-up, nearly 79% of women receiving Herceptin remained cancer-free, a significant increase compared to 73% of women in the observation arm. With regard to safety, it was shown that the incidence of severe cardiac dysfunction associated with  adjuvant Herceptin-based therapy was low

(0.8%). These results confirm the benefit and safety of one year of Herceptin treatment in women with HER2 positive tumors despite the substantive crossover of patients from the observation group to active treatment. The present analysis also suggests that women who crossed over derived benefit from Herceptin even if they started Herceptin therapy late after completion of adjuvant chemotherapy.

The HERA study is ongoing and final results are expected in 2011.

About breast cancer

Breast cancer is the most common cancer among women worldwide.2 Each year more than one million new cases of breast cancer are diagnosed worldwide, and nearly 400,000 people will die of the disease annually.3

In HER2 positive breast cancer, increased quantities of the HER2 protein are present on the surface of the tumour cells. This is known as ‘HER2 positivity’ and affects approximately 20-25% of women with breast cancer.

About Herceptin

Herceptin is a humanised antibody designed to target and block the function of HER2, a protein produced by a specific gene with cancer-causing potential. The mode of action of Herceptin is unique in that it activates the body’s immune system and suppresses HER2 to target and destroy the tumour. Herceptin has demonstrated unprecedented efficacy in treating both early and advanced (metastatic) HER2 positive breast cancer. Given on its own as monotherapy as well as in combination with or following standard chemotherapy, Herceptin has been shown to improve response rates, disease-free survival and overall survival while maintaining quality of life in women with HER2 positive breast cancer.

Herceptin received approval for use in the European Union for advanced (metastatic) HER2 positive breast cancer in 2000, and for early (adjuvant) HER2 positive breast cancer in 2006. In the advanced (metastatic) setting, Herceptin is approved for use as a first-line therapy in combination with paclitaxel where anthracyclines are unsuitable, as first-line therapy in combination with docetaxel, and as a single agent in third-line therapy. It is also approved for use in combination with an aromatase inhibitor for the treatment of post-menopausal patients with HER2 and hormone receptor co-positive metastatic breast cancer. In the early (adjuvant) setting, Herceptin is approved for use following standard (adjuvant) chemotherapy.

Herceptin is marketed in the United States by Genentech, in Japan by Chugai and internationally by Roche. Since 1998, Herceptin has been used to treat nearly 600,000 women with HER2 positive breast cancer 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 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 2008 sales by the Pharmaceuticals Division totaled 36.0 billion Swiss francs, and the Diagnostics Division posted sales of 9.7 billion Swiss francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invested nearly 9 billion Swiss francs in R&D in 2008. Worldwide, the Group employs about 80,000 people. Additional information is available on the Internet at www.roche.com.

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

About BIG

The Breast International Group (BIG) is an international non-profit organisation for academic breast cancer research groups from around the world, based in Brussels, Belgium. Created by leading European opinion leaders in 1996, BIG now constitutes a network of 44 groups based in Europe, Canada, Latin America, and the Asia-Pacific region. These research entities are tied to approximately 3000 specialised hospitals and research centres worldwide. BIG also collaborates with the U.S. National Cancer Institute (NCI) and North American collaborative groups, with BIG and the North Americans together representing an impressive integrating force in the breast cancer research arena. To make significant scientific advances in breast cancer research, reduce the wasteful duplication of effort, and optimally serve those affected by the disease, large-scale cooperation is crucial. Therefore BIG facilitates breast cancer research at international level, by stimulating cooperation between its members and other academic networks, and collaborating with, but working independently from, the pharmaceutical industry.

References
1) Smith I, Procter M, Gelber RD, et al., Lancet 2007; 369:29-36  
2) World Health Organization, http://www.who.int/cancer/detection/breastcancer/en/
3) Ferlay J, et al., GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No.5, Version 2.0. IARCPress, Lyon, 2004. 2004