Investigational Cancer Drug Pertuzumab Shows Promising Results in Advanced Breast Cancer When Combined with Herceptin

Update: Perjeta (pertuzumab) Now FDA Approved - June 8, 2012
Investigational cancer drug Pertuzumab shows promising results in advanced breast cancer when combined with Herceptin Phase III development initiated

BASEL, Switzerland, June 4, 2007-Early clinical results from Roche's trial of the exciting new cancer medicine pertuzumab, a HER dimerisation inhibitor, show substantial anti-tumour activity in patients with pre-treated HER2 positive breast cancer, when combined with Herceptin. The study showed that one in five patients responded to pertuzumab treatment and one in five also had stabilization of their disease lasting 6 months or more. The results are particularly promising, as the benefits were seen in patients with late stage cancer, whose options for further treatment are limited.

"This is potentially good news for patients whose HER2 positive breast cancer is not responding to current treatments," commented Dr Jose Baselga, lead investigator, Vall d'Hebron University Hospital, Barcelona, Spain. "We are encouraged by the initial results from this trial and are continuing to further recruit patients into the second stage of the study."

The phase II study presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, investigated the combination of two of Roche's HER2 targeted agents, pertuzumab and Herceptin, in patients with HER2 positive metastatic breast cancer whose disease had progressed during treatment with Herceptin plus chemotherapy (1).

Pertuzumab is the first in a new innovative class of targeted agents known as HER dimerization inhibitors (HDIs). The drug inhibits the 'pairing' or dimerization of the protein HER2 with other HER family receptors (HER1, HER2, HER3, and HER4). This interaction is believed to play an important role in the growth and formation of several different cancer types. Pertuzumab in combination adds to the activity of Herceptin due to its different mode of action. "The positive results from this study have enabled us to make the decision to progress to phase III development of pertuzumab in breast cancer," commented Jean-Jacques Garaud, Head of Development, Roche. "We will be investigating the effectiveness of pertuzumab in the metastatic setting and also exploring its use in early breast cancer prior to surgical removal of the tumour."

About the study This is a non-randomised Phase II study, conducted in two-stages: patients were assessed to ensure that the therapy is tolerable and that there is a reasonable minimum level of activity. Eligible patients must have measurable, centrally-tested progressive HER2 positive breast cancer and had received up to 3 courses of prior chemotherapy plus Herceptin and the disease must have progressed during Herceptin therapy . During the study patients received Herceptin i.v weekly or every 3 weeks at 2 mg/kg or 6 mg/kg respectively and 420mg of pertuzumab i.v. every 3 weeks after a loading dose of 840mg. The criteria to proceed to the 2nd stage were: > 2 partial responses (PR), or 1 PR and 12 patients with stable disease (SD), or 13 patients with SD.

Out of 33 patients who had passed the first assessment point at the time of the data cut off, 1 had a complete response and 5 had partial responses giving a response rate of 18.2%. A further 7 patients have had stabilization of disease lasting 6 months or more (21.2%). Recruitment into stage 2 of the trial is ongoing.

As well as evaluating pertuzumab in breast cancer Roche and Genentech are evaluating pertuzumab in ovarian cancer in combination with other therapies. Results from a phase II platinum resistant ovarian cancer study will be presented at ASCO on Sunday 3rd June 1-4pm.

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. 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.' High levels of HER2 are present in a particularly aggressive form of the disease which responds poorly to chemotherapy. Research shows that HER2-positivity affects approximately 20-30 percent of women with breast cancer.

About pertuzumab Pertuzumab is a humanized monoclonal antibody designed to bind to the HER2 receptor and inhibit the ability of HER2 to interact with other HER family members (HER1, HER2, HER3, and HER4) on the surface of cancer cells. The HER signaling pathway plays a role in the formation and growth of numerous cancers, and previous clinical trials of pertuzumab in a single agent setting had suggested clinical activity - including stable disease - in heavily pretreated patients with advanced ovarian and breast cancers. Genentech and Roche are evaluating pertuzumab in solid tumors (ovarian and breast cancers), and in combination with other therapies.

About Herceptin (trastuzumab) 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. It has demonstrated efficacy in treating both early and advanced (metastatic) 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 HER2-positive breast cancer in 2006. In the advanced setting, Herceptin is now 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. In May 2007, Herceptin received European approval for use in combination with anastrazole for the treatment of women with advanced HER2-positive breast cancer that is also hormone receptor positive.

In the early 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 400,000 HER2-positive breast cancer 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 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, a market leader in virology and active in other major therapeutic areas such as autoimmune diseases, inflammation, metabolism and central nervous system. In 2006 sales by the Pharmaceuticals Division totalled 33.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.7 billion Swiss francs. Roche employs roughly 75,000 worldwide 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 at www.roche.com.

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

- About Roche: www.roche.com - About Genentech: www.gene.com - About cancer: www.health-kiosk.ch - Roche in Oncology: http://www.roche.com/pages/downloads/company/pdf/mboncology05e.pdf

References (1)Baselga J. et al., Objective response rate in a Phase II multicenter trial of pertuzumab (P), a HER2 dimerization inhibiting monoclonal antibody, in combination with trastuzumab (T) in patients (Pts) with HER2 positive metastatic breast cancer (MBC) which had progressed during trastuzumab therapy Abstract 1004. American Society of Clinical Oncology Annual Meeting 2007. (2) World Health Organization, http://www.who.int/cancer/detection/breastcancer/en/

Roche Group Media Office Phone: +41 61 688 8888 / e-mail: basel.mediaoffice@roche.com - Daniel Piller (Head of Roche Group Media Office) - Katja Prowald (Head of Science Communications) - Martina Rupp - Baschi Dürr - Claudia Schmitt

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Posted: June 2007

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