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Basel, 23 September , 2009

New data presented at ECCO/ESMO confirms benefits of bevacizumab (Avastin®) based therapy for the first-line treatment of metastatic breast cancer

This update outlines data on bevacizumab in metastatic breast cancer presented at the joint ECCO 15  and ESMO 34  congress in Berlin 20-24 September, 2009.  New data includes:

• Safety and efficacy data from the largest (n=2,251) multinational safety study of Avastin in mBC. The ATHENA study recruited a broad patient population representative of general oncology practice.
• Results from quality of life (QoL) exploratory analysis from the phase III AVADO study indicating that patients receiving combination therapy generally experienced significantly less decline in QoL compared to chemotherapy alone.
• A PFS analysis of efficacy across pre-specified patient sub-groups in the phase III RIBBON-1 study which shows that overall treatment effect of bevacizumab combined with chemotherapy is seen across different patient sub-groups.

ATHENA ¹

Multinational study (n=2,251) of first-line bevacizumab plus taxane-based chemotherapy for locally recurrent or metastatic breast cancer. Patients were treated with bevacizumab 10mg/kg q2w or 15mg/kg q3w combined with a taxane (alone or with another chemotherapy) or non-anthracycline chemotherapy according to physician decision.

Data presented

• No new safety signals for bevacizumab were observed in the study
  - Hypertension (grade 3 and above) was seen in 4.4% of patients
  - Grade 3 and above bleeding occurred in 1.4% of patients
• Safety and efficacy of bevacizumab combined with taxane based chemotherapy was similar to E2100 and AVADO results.

Clinical Relevance

• Safety and efficacy of bevacizumab based therapy confirmed in patient population representative of general oncology practice.

“Three phase III studies have already shown that bevacizumab brings significant benefits to patients in the first-line treatment of metastatic breast cancer,” commented Professor Cortes-Funes, Department of Medical Oncology, University Hospital 12 de Octubre, Madrid and lead author of the ATHENA data presented at ECCO/ESMO. “ATHENA provides even more evidence of this in a real world population, representative of patients we see every day.”

AVADO ²

International phase III trial (n=736). Eligible patients did not receive previous chemotherapy for their locally recurrent or metastatic breast cancer and were randomised to one of three arms:  bevacizumab 7.5mg/kg q3w with 100mg/m2 docetaxel chemotherapy; bevacizumab 15mg/kg q3w with docetaxel 100mg/m2 chemotherapy; or placebo with docetaxel 100mg/m2 chemotherapy.  Patients completed a Functional Assessment of Cancer Therapy – Breast (FACT-B) questionnaire.

Data presented

• Patients treated with bevacizumab in combination with docetaxel as first-line treatment for mBC experienced significantly less decline in QoL compared with those in the control arm.
  - Mean  QoL scores were significantly higher with 15mg/kg bevacizumab than with placebo at most time points
• This is consistent with data from the E2100 study which demonstrated a statistically significant greater decline in QoL in the control arm compared with the bevacizumab treatment arm.³

Clinical Relevance

• AVADO previously demonstrated that Avastin in combination with docetaxel significantly increased PFS over docetaxel alone. ⁴
• This latest analysis shows that the combination of bevacizumab with docetaxel does not add to the burden for patients receiving taxane therapy for mBC.

RIBBON-1 ⁵

International phase III trial (n=1,237).  Patients did not receive previous chemotherapy for their HER2-negative locally recurrent or metastatic breast cancer. RIBBON-1 comprised of two independently powered treatment groups investigating either Avastin or placebo in combination with 7 distinct chemotherapy regimens.

Data presented

The combination of bevacizumab with standard cytotoxic therapy (including anthracycline and capecitabine chemotherapies) improves PFS compared to chemotherapy alone across patient sub-groups with differing clinical characteristics and disease history.

• Hazard ratios favoured bevacizumab arms of the respective chemotherapies in all subgroups

Clinical Relevance

• Third phase III study to demonstrate that bevacizumab based therapy significantly improves PFS over chemotherapy alone.
• Overall treatment effect is seen across pre-specified clinically relevant subgroups

Bevacizumab is not currently licensed for use with anthracyclines or capecitabine.  In Europe it is currently licensed for first-line treatment of patients with metastatic breast cancer in combination with paclitaxel or docetaxel.⁴

Bevacizumab has a well-established tolerability profile and the most frequently observed adverse drug reactions in clinical trials were hypertension, fatigue, neuropathy and proteinuria. The most common side effects are generally manageable, for example, hypertension can generally be managed with conventional antihypertensive treatment.

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 2008, Roche had over 80,000 employees worldwide and invested almost 9 billion Swiss francs in R&D. The Group posted sales of 45.6 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.

REFERENCES
1) Cortes-Funes H et al. Multinational study (n=2041) of first-line bevacizumab (Bev) plus taxane-based chemotherapy (CT) for locally recurrent or metastatic breast cancer (LR/mBC): updated results of MO19391. Poster Discussion on 23 September 2009, ECCO 15 and ESMO 34.
2) Greil R et al. Quality of life (QoL) in patients (pts) treated with bevacizumab (BV) and taxane therapy for locally recurrent (LR) or metastatic breast cancer (mBC). Poster Discussion on 23 September 2009, ECCO 15 and ESMO 34.
3) FDA Oncology Drug Advisory Committee (ODAC). Data available at http://www.fda.gov/ohrms/dockets/ac/07/slides/2007-4332s1-03-Genentech.ppt.
4) Avastin Summary of Product Characteristics
5) Dieras V et al. Efficacy in patient subgroups in RIBBON-1, a randomized, double-blind, Phase III trial of chemotherapy with or without bevacizumab (B) for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer (MBC). Poster Discussion on 23 September 2009, ECCO 15 and ESMO 34.