Health Canada approves HERCEPTIN® for patients with HER2-positive advanced
stomach cancer

First targeted biological therapy to show survival benefit in stomach cancer

MISSISSAUGA, ON, Aug. 9 /CNW/ - Roche announced today that after priority review, Health Canada has approved HERCEPTIN® (trastuzumab), in combination with XELODA® (capecitabine) or intravenous 5-fluorouracil and cisplatin, for the first-line treatment of patients with HER2-positive metastatic adenocarcinoma of the stomach (gastric cancer) or gastro-esophageal cancer. This approval will drive a significant change in the treatment of this devastating disease, allowing patients with stomach cancer to benefit from this life-extending treatment.

The approval is based on the results from the international ToGA trial, which showed that HERCEPTIN significantly prolongs the lives of patients with this aggressive cancer without compromising quality of life. HERCEPTIN is the first targeted biological therapy to show a survival benefit in advanced stomach cancer. In patients with high levels of HER2 expression, the overall survival was 16 months in the group receiving HERCEPTIN versus 11.8 months (on average) for patients receiving chemotherapy alone.ⁱ

"As the first biological therapy to show a significant overall survival benefit in advanced stomach cancer, HERCEPTIN represents a new therapeutic option beyond chemotherapy for Canadians living with this horrible disease," said Dr. Christine Brezden-Masley, Staff Medical Oncologist, St. Michael's Hospital and Assistant Professor, University of Toronto Clinical Leader, Oncology Clinical Research Group. "The approval of HERCEPTIN for HER2-positive metastatic stomach cancer provides a much-needed therapeutic alternative which is generally well-tolerated and does not compromise quality of life."

Advanced stomach cancer is associated with a poor prognosis; the median survival time after diagnosis is approximately 10 to 11 months with currently available therapies.ⁱⁱ Approximately 15 to 19 per cent of stomach tumours show high levels of HER2.^iii,iv

"The approval of HERCEPTIN for patients with advanced stomach or esophageal cancer represents a significant advance in personalized medicine," said Dr. Catherine Streutker, Director of Surgical Pathology, Department of Laboratory Medicine, St. Michael's Hospital and Assistant Professor, University of Toronto. "HER2 testing these patients enables physicians to quickly optimize treatment outcomes, as it allows healthcare resources to be directed towards those patients who are most likely to benefit from HERCEPTIN, while those who are not can be redirected to other treatment options."

Stomach cancer is the second most common cause of cancer-related death in the world and is the fourth most commonly diagnosed cancer.^v According to the Canadian Cancer Society, in 2010 there will be 2,900 new cases of stomach cancer and 1,850 Canadians will die from the disease.^vi The highest estimated rates of incidence of stomach cancer for 2010 will occur in Ontario (1,090), Quebec (800), British Columbia (360) and Alberta (255).^vii

About ToGA
ToGA is the first randomized Phase III trial investigating the use of HERCEPTIN in patients with inoperable locally advanced, recurrent and/or metastatic HER2-positive gastric or gastroesophageal cancer. Approximately 3,800 patients were tested for HER2-positive tumours and 584 patients with HER2-positive disease were enrolled into the study. The rationale for conducting this trial was based on the knowledge that the targeted therapy HERCEPTIN has demonstrated unprecedented efficacy in the treatment of HER2-positive breast cancer. In addition, the overexpression of HER2 was also observed in stomach cancer. Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumour growth and progression.

In the ToGA study, patients were randomized to receive one of the following regimens as their first line of treatment:

• A fluoropyrimidine (XELODA or intravenous 5-FU) and cisplatin every three weeks for six cycles. Most patients were receiving XELODA and cisplatin as chemotherapy.
• The same chemotherapy as above (six cycles) plus HERCEPTIN every three weeks until progression.

The primary objective of the study was to demonstrate superiority in overall survival of the HERCEPTIN-containing treatment arm compared to the chemotherapy alone arm. The pre-planned interim analysis was triggered by the occurrence of 347 events. Secondary endpoints for the study included progression-free survival, overall response rate, duration of response, safety and quality of life. In the ToGA study, no new or unexpected side effects were observed. For overall survival, the Hazard Ratio was 0.74 (CI 0.60, 0.91) with a highly significant p-value of p=0.0046. HERCEPTIN increased the median overall survival time by 2.7 months to 13.8 months (intent to treat patient group, defined as IHC3+ or FISH-positive, represented 22 per cent of patients tested for HER2 in the ToGA study). The response rate was increased with HERCEPTIN from 34.5 to 47.3 per cent. Patients with tumours exhibiting high levels of HER2 (IHC3+ or IHC2+/FISH-positive, 16 per cent of patients tested for HER2 in the ToGA study) experienced even greater benefit from the addition of HERCEPTIN. For these patients, overall survival in the study was 16 months on average versus 11.8 months for patients receiving chemotherapy alone.

About HERCEPTIN
HERCEPTIN is a humanized monoclonal 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 is marketed in Canada and internationally by Roche, in the United States by Genentech and in Japan by Chugai. Since 1998, HERCEPTIN has been used to treat more than 740,000 patients with HER2-positive breast cancer worldwide.

About XELODA
XELODA is a highly effective targeted oral chemotherapy offering patients a survival advantage when taken on its own or in combination with other anticancer drugs. XELODA uniquely activates the cancer-killing agent 5-FU (5-fluorouracil) directly inside the cancer cells so avoiding damage to healthy cells. XELODA tablets can be taken by patients in their own home, reducing the number of hospital visits.

Licensed and marketed by Roche in more than 100 countries worldwide, XELODA has more than ten years of proven clinical experience providing an effective and flexible treatment option to over 1.8 million people with cancer. XELODA is currently approved in adjuvant colon cancer, metastatic colorectal cancer and breast cancer in Canada.

Roche Personalized Healthcare: Fitting treatments to patients
Different people respond differently to medicines. The aim of Roche Personalized Healthcare (PHC) is to target treatments to the patients most likely to benefit. This means tailoring treatments to specific patient sub-groups who share similar characteristics in their genetic makeup or in the molecular nature of their disease. This approach has enormous potential to make healthcare better, safer and more effective, with benefits for patients, physicians, payers, and society at large.

HERCEPTIN treatment in breast cancer is a case in point: Measuring the levels of the HER2 protein in breast cancer cells with specific tests such as the assays from Roche Tissue Diagnostics (Ventana) reliably identifies patients who are likely to respond to HERCEPTIN, a medicine that specifically targets HER2. Roche is also applying this approach to the diagnosis and the treatment of HER2-positive metastatic gastric cancer with HERCEPTIN.

About Roche
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world's largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche's personalized healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 81,500 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

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References

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ⁱ Van Cutsem et al. Abstract #7BA ECCO/ESMO 2009.
ⁱⁱ Ohtsu A. Chemotherapy for metastatic gastric cancer: past, present, and future. J Gastroenterol 2008;43:256-264.
ⁱⁱⁱHofmann M, Stoss O, Shi D, Buttner R, van d, V, Kim W et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008; 52(7):797-805.
^iv Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci 2006; 51(8):1371-1379.
^v American Cancer Society. Global Cancer Facts & Figures 2007. http://www.cancer.org/acs/groups/content/@nho/documents/document/caff2007pwsecuredpdf.pdf. Accessed June 9, 2010.
^vi Canadian Cancer Society. Canadian Cancer Statistics 2010. http://www.cancer.ca/Canada-wide/About%20cancer/Cancer%20statistics/~/media/CCS/Canada%20wide/Files%20List/English%20files%20heading/PDF%20-%20Policy%20-%20Canadian%20Cancer%20Statistics%20-%20English/Canadian%20Cancer%20Statistics%202010%20-%20English.ashx. Accessed June 9, 2010.
^vii Canadian Cancer Society. Canadian Cancer Statistics 2010. http://www.cancer.ca/Canada-wide/About%20cancer/Cancer%20statistics/~/media/CCS/Canada%20wide/Files%20List/English%20files%20heading/PDF%20-%20Policy%20-%20Canadian%20Cancer%20Statistics%20-%20English/Canadian%20Cancer%20Statistics%202010%20-%20English.ashx. Accessed June 9, 2010.

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