Pertuzumab and Herceptin plus chemotherapy significantly improved the rate of complete tumour disappearance in study of women with newly diagnosed, early-stage HER2-positive breast cancer

Phase II study evaluating a novel targeted combination regimen showed promising results in the neoadjuvant (pre-surgery) setting

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from the NEOSPHERE trial, a Phase II neoadjuvant study evaluating the effect of a novel combination regimen of pertuzumab and Herceptin (trastuzumab) plus chemotherapy (docetaxel) in women with early-stage HER2-positive breast cancer. The data, presented at the CTRC-AACR San Antonio Breast Cancer Symposium (SABCS), showed that the two antibodies plus docetaxel given in the neoadjuvant setting prior to surgery significantly improved the rate of complete tumour disappearance (pathological complete response rate, pCR, of 45.8 percent) in the breast by more than half compared to Herceptin plus docetaxel (pCR of 29. 0 percent), p=0.014.

“The findings of the NEOSPHERE study suggested that this new approach was effective for early HER2-positive breast cancer,” said Professor Luca Gianni, Principal Investigator of the study and Director of Medical Oncology at the National Cancer Institute in Milan, Italy. “The combination of pertuzumab and Herceptin plus chemotherapy had a substantial effect on HER2-positive breast cancer tumours after just four cycles (12 weeks)of neoadjuvant use.”

The combination of pertuzumab and Herceptin plus docetaxel was not associated with a significant increase in side effects or cardiac risk compared to Herceptin and chemotherapy. Most common severe side effects were neutropenia (low white blood cell count), fever that was associated with neutropenia and diarrhoea.

“We are committed to developing new medicines that make a difference for people living with cancer and to advancing personalized treatments,” said Hal Barron, Head of Global Development and Chief Medical Officer at Roche. “The clinical data presented today (at SABCS) add to the body of evidence that this novel targeted regimen plus chemotherapy may improve outcomes in women with HER2-positive breast cancer.”

Based on these findings, Roche plans to initiate a Phase III study in HER2-positive early (adjuvant) breast cancer in 2011. In addition, CLEOPATRA, a Phase III study evaluating the efficacy and safety profile of pertuzumab and Herceptin plus chemotherapy as a first line regimen in patients with HER2-positive metastatic breast cancer, completed enrolment in Q2 2010 and results are expected by the end of 2011.
About the NEOSPHERE trial

The NEOSPHERE study (Neoadjuvant Study of Pertuzumab and Herceptin in an Early Regimen Evaluation) is a randomized multicentre, international Phase II study that was conducted in 78 centres worldwide (except the USA) in 417 women with newly diagnosed HER2-positive early, inflammatory or locally advanced breast cancer who had never received Herceptin. Prior to surgery (neoadjuvant treatment) these women were randomized to four study arms. The primary endpoint was complete tumour disappearance at time of surgery (pathological complete response , pCR) and the results were:

* pCR of 29,0 percent for Herceptin and docetaxel
* pCR of 45,8 percent for Herceptin, pertuzumab and docetaxel
* pCR of 16,8 percent for Herceptin and pertuzumab
* pCR of 24,0 percent for pertuzumab and docetaxel

Secondary endpoints include clinical response, time to clinical response, safety profile, disease free survival, breast conserving surgery rate and biomarker assessment.
About Breast Cancer

Breast cancer is the most common cancer among women worldwide2.Each year about 1.4 million new cases of breast cancer are diagnosed worldwide, and over 450,000 people will die of the disease annually2.

In HER2-positive breast cancer, increased quantities of the HER2 receptor are present on the surface of the tumour cells. This is known as ‘HER2 positivity’ and affects approximately 15-25 percent of women with breast cancer.
About pertuzumab

Pertuzumab is a monoclonal antibody being studied in early stage and metastatic HER2-positive breast cancer. It is a novel targeted medicine called a “HER2 dimerisation inhibitor” (HDI). HER dimerisation (pairing) is believed to play an important role in the growth and formation of several different cancer types. Pertuzumab is the first investigational medicine designed to specifically prevent the HER2 receptor from pairing with other HER receptors (EGFR/HER1, HER2, HER3, HER4). Interfering with HER2’s ability to collaborate with other HER family receptors, pertuzumab blocks cell signaling, which may ultimately inhibit cancer cell growth or lead to the death of the cancer cell. The modes of action of pertuzumab and Herceptin are believed to complement each other. Both bind to the HER2 receptor but in different regions. By doing so it is hypothesised that the two antibodies in combination may provide a more comprehensive blockade of the HER signaling pathways than either agent alone.
About Herceptin

Herceptin is a 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 the United States by Genentech, in Japan by Chugai and internationally by Roche. Since 1998, Herceptin has been used to treat more than 740,000 patients with HER2-positive breast cancer worldwide.
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 personalised 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 80,000 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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1) Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10 [Internet].Lyon, France: International Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr
2) Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10 [Internet].Lyon, France: International Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr