Investor Update
Basel, 18 December 2006
Combination of Herceptin and Avastin shows promise in treatment of aggressive form of breast cancer
Exciting news for physicians and patients in fight against HER2-positive breast cancer presented at San Antonio Breast Cancer Symposium
Exciting clinical study results show for the first time that combining two humanised antibodies, Herceptin (trastuzumab) and Avastin (bevacizumab) has the potential to provide a powerful new weapon in the fight against a particularly aggressive form of breast cancer. The phase II study presented at the San Antonio Breast Cancer Symposium (SABCS) investigated the first-line treatment of HER2-positive advanced (or ‘metastatic’) breast cancer. More than half (54%) of the patients in the study showed a complete or partial response to treatment (tumour shrinkage).1 The study results also showed that the safety profile of the Herceptin/Avastin combination was acceptable and importantly lacked the typical chemotherapy-related side effects.
HER2-positive breast cancer affects approximately 20-30 percent2 of women with breast cancer. It demands special attention because the tumours are typically fast-growing and there is a high likelihood of relapse.
“These positive results confirm that adding Avastin to Herceptin could provide extra benefit for patients with this particularly aggressive form of breast cancer,” said Andreas Abt, Global Business Director for Roche Oncology. “Using novel anti-cancer therapies to form a multi-pronged attack on the disease is an important step forward in the treatment of breast cancer and a phase III study is currently ongoing.”
Following highly encouraging pre-clinical and Phase I data3, this Phase II study set out to investigate the possibility of fighting the tumour from two angles: by blocking the HER2 protein which gives the cancer instructions to grow, and by starving the cancer from its blood supply. Herceptin specifically targets HER2, has multiple modes of action, providing different ways to fight the cancer, and has been shown to improve survival in early and metastatic HER2-positive breast cancer. Avastin prevents formation of new blood vessels (‘angiogenesis’), so starving the tumour of the blood supply that is critical for its growth, survival and spread. Avastin is the first and only anti-angiogenic agent that has shown survival benefits in four major tumour types: colorectal, breast, lung and renal cell cancer.
A phase III trial investigating the clinical benefits of adding Avastin to Herceptin plus one of the standard chemotherapies (docetaxel) for the first-line treatment of advanced breast cancer is ongoing. In addition, based on the strong pre-clinical rationale and clinical data, the investigation of the Avastin plus Herceptin combination in the adjuvant HER2-positive breast cancer setting is in planning.
About the study with abstract # 301
The objectives of this phase II study were to evaluate the clinical efficacy of Herceptin plus Avastin in the first-line treatment of HER2-positive locally recurrent surgically unresectable, or metastatic breast cancer patients, and to evaluate the safety profile of this combination. Herceptin was administered at a dose of 4 mg/kg as loading dose then 2 mg/kg weekly plus Avastin 10 mg/kg q 2 weeks. The study is ongoing and interim data of 37 patients were presented.
Efficacy:
• Responses have been documented in 20 of 37 (~54%) evaluable patients; 1 was a complete response (confirmed by a second tumour assessment), 19 were partial responses of which 13 were confirmed
• 31/37 (~84%) patients showed a response or had stable disease at their first post-baseline tumour assessment
Safety:
• Grade III/IV drug-related adverse events: dyspnea (1 grade 3), left ventricular dysfunction (1 grade 4), hypertension (7 grade 3) and proteinuria (1 grade 3).
• Most common grade I/II adverse events: epistaxis (nose bleed) 6/0;AST increase 5/1; fatigue 1/5; headache 4/3 and hypertension 2/6
• Cardiac toxicity adverse events were observed in 13 patients: 7 grade 1, 5 grade 2, 0 grade 3 and 1 grade 4. Stringent cardiac safety surveillance will be pursued.
Pre-clinical and phase I data: In xenograft models, synergistic effects were observed when Herceptin was given in combination with Avastin. In a phase I dose-escalation study of Herceptin plus Avastin, (Pegram, et al. SABCS 2004), pharmacokinetic (PK) analysis indicated co-administration of these two humanized monoclonal antibodies did not alter the PK of either agent. Clinical responses were observed in 5 of 9 patients in the phase I, including one patient with prior disease progression on Herceptin. Overall the responses were durable with 3 patients continuing beyond 1 year on the study.
About breast cancer
Breast cancer is the most common cancer among women worldwide.4 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.5
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 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 especially 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 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 over 350,000 HER2-positive breast cancer patients worldwide.
About Avastin (bevacizumab)
Avastin is the first treatment that inhibits angiogenesis – the growth of a network of blood vessels that supply nutrients and oxygen to cancerous tissues. Avastin targets a naturally occurring protein called Vascular Endothelial Growth Factor (VEGF), a key mediator of angiogenesis, thus choking off the blood supply that is essential for the growth of the tumour and its spread throughout the body (metastasis). Avastin is the first and only anti-angiogenic agent that has shown overall and/or progression-free survival benefits in four major cancer types: colorectal, breast, lung and renal cell cancer.
In Europe, Avastin was approved in January 2005 and in the US in February 2004 for the first-line treatment of patients with metastatic colorectal cancer. It received two additional approvals in the US: in June 2006 for the second-line treatment of patients with metastatic colorectal cancer and in October 2006 for the first-line treatment of advanced non-small cell lung cancer (NSCLC). The first filing for Avastin in Japan occurred in April 2006 for the treatment of metastatic colorectal cancer. Avastin was filed with European Health Authorities for the first-line treatment of advanced breast cancer in July 2006 and the first-line treatment of advanced NSCLC in August 2006.
Roche and Genentech are pursuing a comprehensive clinical programme investigating the use of Avastin in various tumour types (including colorectal, breast, lung, pancreatic cancer, ovarian cancer, renal cell carcinoma and others) and different settings (advanced and adjuvant i.e. post-operation). The total development programme is expected to include over 40,000 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 a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2005 sales by the Pharmaceuticals Division totalled 27.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.2 billion Swiss francs. Roche employs roughly 70,000 people in 150 countries 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 (www.roche.com).
Access video clips, in broadcast standard, free of charge.
Combination of Herceptin and Avastin shows promise in treatment of aggressive form of breast cancer
Exciting news for physicians and patients in fight against HER2-positive breast cancer presented at San Antonio Breast Cancer Symposium
Exciting clinical study results show for the first time that combining two humanised antibodies, Herceptin (trastuzumab) and Avastin (bevacizumab) has the potential to provide a powerful new weapon in the fight against a particularly aggressive form of breast cancer. The phase II study presented at the San Antonio Breast Cancer Symposium (SABCS) investigated the first-line treatment of HER2-positive advanced (or ‘metastatic’) breast cancer. More than half (54%) of the patients in the study showed a complete or partial response to treatment (tumour shrinkage).1 The study results also showed that the safety profile of the Herceptin/Avastin combination was acceptable and importantly lacked the typical chemotherapy-related side effects.
HER2-positive breast cancer affects approximately 20-30 percent2 of women with breast cancer. It demands special attention because the tumours are typically fast-growing and there is a high likelihood of relapse.
“These positive results confirm that adding Avastin to Herceptin could provide extra benefit for patients with this particularly aggressive form of breast cancer,” said Andreas Abt, Global Business Director for Roche Oncology. “Using novel anti-cancer therapies to form a multi-pronged attack on the disease is an important step forward in the treatment of breast cancer and a phase III study is currently ongoing.”
Following highly encouraging pre-clinical and Phase I data3, this Phase II study set out to investigate the possibility of fighting the tumour from two angles: by blocking the HER2 protein which gives the cancer instructions to grow, and by starving the cancer from its blood supply. Herceptin specifically targets HER2, has multiple modes of action, providing different ways to fight the cancer, and has been shown to improve survival in early and metastatic HER2-positive breast cancer. Avastin prevents formation of new blood vessels (‘angiogenesis’), so starving the tumour of the blood supply that is critical for its growth, survival and spread. Avastin is the first and only anti-angiogenic agent that has shown survival benefits in four major tumour types: colorectal, breast, lung and renal cell cancer.
A phase III trial investigating the clinical benefits of adding Avastin to Herceptin plus one of the standard chemotherapies (docetaxel) for the first-line treatment of advanced breast cancer is ongoing. In addition, based on the strong pre-clinical rationale and clinical data, the investigation of the Avastin plus Herceptin combination in the adjuvant HER2-positive breast cancer setting is in planning.
About the study with abstract # 301
The objectives of this phase II study were to evaluate the clinical efficacy of Herceptin plus Avastin in the first-line treatment of HER2-positive locally recurrent surgically unresectable, or metastatic breast cancer patients, and to evaluate the safety profile of this combination. Herceptin was administered at a dose of 4 mg/kg as loading dose then 2 mg/kg weekly plus Avastin 10 mg/kg q 2 weeks. The study is ongoing and interim data of 37 patients were presented.
Efficacy:
• Responses have been documented in 20 of 37 (~54%) evaluable patients; 1 was a complete response (confirmed by a second tumour assessment), 19 were partial responses of which 13 were confirmed
• 31/37 (~84%) patients showed a response or had stable disease at their first post-baseline tumour assessment
Safety:
• Grade III/IV drug-related adverse events: dyspnea (1 grade 3), left ventricular dysfunction (1 grade 4), hypertension (7 grade 3) and proteinuria (1 grade 3).
• Most common grade I/II adverse events: epistaxis (nose bleed) 6/0;AST increase 5/1; fatigue 1/5; headache 4/3 and hypertension 2/6
• Cardiac toxicity adverse events were observed in 13 patients: 7 grade 1, 5 grade 2, 0 grade 3 and 1 grade 4. Stringent cardiac safety surveillance will be pursued.
Pre-clinical and phase I data: In xenograft models, synergistic effects were observed when Herceptin was given in combination with Avastin. In a phase I dose-escalation study of Herceptin plus Avastin, (Pegram, et al. SABCS 2004), pharmacokinetic (PK) analysis indicated co-administration of these two humanized monoclonal antibodies did not alter the PK of either agent. Clinical responses were observed in 5 of 9 patients in the phase I, including one patient with prior disease progression on Herceptin. Overall the responses were durable with 3 patients continuing beyond 1 year on the study.
About breast cancer
Breast cancer is the most common cancer among women worldwide.4 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.5
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 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 especially 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 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 over 350,000 HER2-positive breast cancer patients worldwide.
About Avastin (bevacizumab)
Avastin is the first treatment that inhibits angiogenesis – the growth of a network of blood vessels that supply nutrients and oxygen to cancerous tissues. Avastin targets a naturally occurring protein called Vascular Endothelial Growth Factor (VEGF), a key mediator of angiogenesis, thus choking off the blood supply that is essential for the growth of the tumour and its spread throughout the body (metastasis). Avastin is the first and only anti-angiogenic agent that has shown overall and/or progression-free survival benefits in four major cancer types: colorectal, breast, lung and renal cell cancer.
In Europe, Avastin was approved in January 2005 and in the US in February 2004 for the first-line treatment of patients with metastatic colorectal cancer. It received two additional approvals in the US: in June 2006 for the second-line treatment of patients with metastatic colorectal cancer and in October 2006 for the first-line treatment of advanced non-small cell lung cancer (NSCLC). The first filing for Avastin in Japan occurred in April 2006 for the treatment of metastatic colorectal cancer. Avastin was filed with European Health Authorities for the first-line treatment of advanced breast cancer in July 2006 and the first-line treatment of advanced NSCLC in August 2006.
Roche and Genentech are pursuing a comprehensive clinical programme investigating the use of Avastin in various tumour types (including colorectal, breast, lung, pancreatic cancer, ovarian cancer, renal cell carcinoma and others) and different settings (advanced and adjuvant i.e. post-operation). The total development programme is expected to include over 40,000 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 a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2005 sales by the Pharmaceuticals Division totalled 27.3 billion Swiss francs, and the Diagnostics Division posted sales of 8.2 billion Swiss francs. Roche employs roughly 70,000 people in 150 countries 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 (www.roche.com).
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Access video clips, in broadcast standard, free of charge.
1)
Pegram MD, et al. Phase II combined biological therapy targeting the HER2 proto-oncogene and the vascular
endothelial growth factor (VEGF) using trastuzumab (T) and bevacizumab (B) as first-line treatment of
HER2-amplified breast cancer. Abstract # 301, San Antonio Breast Cancer Symposium 2006
2)
Harries M, Smith I. The development and clinical use of trastuzumab (Herceptin). Endocr Relat Cancer
9: 75-85, 2002.
3) Pegram, et al. San Antonio Breast Cancer Symposium 2004
4)
World Health Organization, http://www.who.int/cancer/detection/breastcancer/en/
5) Ferlay
J, et al., GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No.5,
Version 2.0. IARCPress, Lyon, 2004. 2004