Media Release

Basel, 8 December 2011

Roche announces positive results of pivotal Phase III study with pertuzumab in HER2-positive metastatic breast cancer

6.1 month improvement in median progression free survival, from 12.4 to 18.5 months

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced results from CLEOPATRA, the first randomised Phase III study of the investigational HER2-targeted medicine pertuzumab. The study compared the combination of pertuzumab, Herceptin (trastuzumab) and docetaxel chemotherapy to Herceptin and docetaxel alone in people with previously untreated HER2-positive metastatic breast cancer (mBC). People who received pertuzumab in combination with Herceptin and chemotherapy experienced a 38 percent reduction in the risk of their disease worsening or death (progression-free survival, or PFS), (HR=0.62; p-value=<0.0001). The median PFS improved by 6.1 months from 12.4 months for Herceptin and chemotherapy to 18.5 months for pertuzumab, Herceptin and chemotherapy. Overall survival (OS) data are currently immature, with a trend in favour of the pertuzumab combination.

No new safety signals were observed and adverse events were consistent with those seen in previous studies of pertuzumab and Herceptin, either in combination or alone. The results will be presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium December 6-10 (Abstract # S5-5), and were featured in the official press program. Data were published yesterday in the online edition of the New England Journal of Medicine. Roche has submitted a Biologics License Application for pertuzumab to the U.S. Food and Drug Administration (FDA) for people with previously untreated, HER2-positive metastatic breast cancer and a Marketing Authorization Application to the European Medicines Agency (EMA) in the same indication.

“We have been studying the HER2 pathway for 30 years to bring personalised medicines to people with HER2-positive breast cancer,” said Hal Barron, M.D., Chief Medical Officer and Head, Global Product Development. These results show we may soon improve on the current standard of care, Herceptin plus chemotherapy, to further help people with this advanced form of the disease.”

The mechanisms of action of pertuzumab and Herceptin are believed to complement each other as both bind to the HER2 receptor but on different regions. This is believed to provide a more comprehensive blockade of HER signalling pathways.

About Pertuzumab

Pertuzumab is a humanized monoclonal antibody being studied in early and advanced stages of HER2-positive breast cancer and advanced HER2-positive gastric cancer. Pertuzumab is unique in that it is designed specifically to prevent the HER2 receptor from pairing with other HER receptors (EGFR/HER1, HER3 and HER4), a process that is believed to play an important role in the growth and formation of several different cancer types. By preventing receptor pairing, pertuzumab is thought to block cell signalling, which may inhibit cancer cell growth or lead to the death of the cancer cell. Binding of pertuzumab to HER2 may also signal the body’s immune system to destroy the cancer cells.

About the CLEOPATRA study

CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) is an international, Phase III, randomised, double-blind, placebo-controlled study. The study evaluated the efficacy and safety profile of pertuzumab combined with Herceptin and chemotherapy compared to Herceptin and chemotherapy alone in 808 people with previously untreated HER2-positive mBC.

Participants in the pertuzumab, Herceptin and chemotherapy arm received:

  • Pertuzumab 840 mg loading dose followed by 420 mg every three weeks
  • Herceptin 8 mg/kg loading dose followed by 6 mg/kg every three weeks
  • Docetaxel 75-100 mg/m2 every three weeks for six cycles or until progression

Participants in the Herceptin and chemotherapy arm received:

  • Herceptin 8 mg/kg loading dose followed by 6 mg/kg every three weeks
  • Docetaxel 75-100 mg/m2 every three weeks for six cycles or until progression

The primary endpoint of the study was PFS as assessed by an independent review committee. Secondary endpoints were overall survival (OS), PFS by investigator assessment, safety profile, overall response rate (ORR), duration of response, time to symptom progression and correlation of biomarkers with clinical outcomes

Study Results

  • There was a significant improvement in PFS for patients who received the combination of pertuzumab, Herceptin and chemotherapy (n=402) compared to those who received Herceptin and chemotherapy alone (n=406) (median PFS 18.5 vs. 12.4 months, HR=0.62, p=<0.0001, according to independent review).
  • The interim OS analysis took place when 43% of events that were planned for final overall survival analysis had occurred. At the time of interim analysis, patients in both treatment arms had been followed for overall survival for a median of 19.3 months. The data showed a trend suggestive of a survival benefit in favour of combining pertuzumab and trastuzumab with docetaxel (HR 0.64; 95% CI, 0.47-0.88; p = 0.0053). As the hazard ratio did not meet the stopping boundary (HR ≤0.603; p ≤0.0012), the overall survival analysis is not statistically significant at this time. The final analysis is expected to take place in 2013.
  • ORR was 80.2 percent and 69.3 percent in the pertuzumab, Herceptin and chemotherapy arm and the Herceptin plus chemotherapy arm, respectively (10.83% difference; 95% CI, 4.2-17.5; p = 0.0011). A fixed-sequence testing hierarchy for efficacy endpoints was specified. Because interim overall survival did not reach statistical significance, the statistical test result for objective response rate is therefore deemed exploratory.
  • Rates of grade ≥3 AEs with >2% difference between arms were observed for neutropenia, febrile neutropenia, and diarrhoea with 48.9%, 13.8%, and 7.9% in the pertuzumab, Herceptin and chemotherapy arm compared with 45.8%, 7.6%, and 5.0% in the Herceptin plus chemotherapy arm.
  • The combination of pertuzumab, Herceptin and chemotherapy was not associated with a higher incidence of cardiac AEs or left ventricular dysfunction compared with Herceptin and chemotherapy.

About Breast Cancer

Breast cancer is the most common cancer among women worldwide1. Each year about 1.4 million new cases of breast cancer are diagnosed worldwide, and over 450,000 women will die of the disease annually1. In HER2-positive breast cancer, increased quantities of the human epidermal growth factor receptor 2 (HER2) are present on the surface of the tumour cells. This is known as “HER2 positivity” and affects approximately 15-20 percent of women with breast cancer2. HER2-positive cancer is a particularly aggressive form of breast cancer3.

About Herceptin

Herceptin (trastuzumab) is a humanised monoclonal antibody, designed to target and block the function of HER2, a protein produced by a specific gene with cancer-causing potential when it is overexpressed. The mode of action of Herceptin is unique in that it activates the body’s immune system and suppresses HER2 signalling 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 overall survival, response rates and disease-free 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 almost 1 million 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 2010, Roche had over 80’000 employees worldwide and invested over 9 billion Swiss francs in R&D. The Group posted sales of 47.5 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
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) Wolff A.C et al. American Society of Clinical Oncology/ College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Arch Pathol Lab Med—Vol 131, January 2007.
3) Slamon D et al. Adjuvant Trastuzumab in HER2-Positive Breast Cancer. N Engl J Med 2011; 365:1273-83.