Second phase III study does not meet primary endpoint
BASEL, SWITZERLAND | September 21, 2010 | Roche today announced the topline results of a second phase III trial evaluating the use of Avastin (bevacizumab) plus chemotherapy in the adjuvant treatment (immediately after surgery) of early-stage colon cancer. The trial compared the efficacy and safety of Avastin plus chemotherapy to chemotherapy alone. The study, known as AVANT, did not meet its primary endpoint of improving disease-free survival in stage III colon cancer. Adverse events were consistent with those previously observed in pivotal trials of Avastin across tumour types for approved indications. These results do not affect Avastin’s approved indications in advanced (metastatic) disease.
In line with the previously reported NSABP C-08 study results that also evaluated Avastin in the early-stage setting, the AVANT study shows that standard chemotherapy plus one year of Avastin is not effective in reducing the risk of relapses in early-stage colon cancer. Unlike the C-08 results, preliminary efficacy data from AVANT numerically favour chemotherapy alone (the control arm). Roche is evaluating the data from these two studies to help define the next steps for the ongoing Avastin adjuvant programme.
“While we originally hoped the significant survival benefit of Avastin seen in metastatic disease in colorectal cancer would be translated to the early setting, it is becoming increasingly clear that the effects of Avastin are different in the metastatic and early disease settings for patients with colon cancer.’’ said Hal Barron, M.D., Head of Global Product Development and Chief Medical Officer at Roche.
Data from the AVANT study will be submitted for presentation at a scientific congress in 2011.
About the AVANT study
AVANT is a randomised, three-arm phase III study in 3,451 patients evaluating Avastin in combination with either capecitabine plus oxaliplatin (XELOX) or fluorouracil/leucovorin with oxaliplatin (FOLFOX-4) versus FOLFOX-4 alone as adjuvant chemotherapy in patients who have undergone surgery for high-risk stage II and stage III colon cancer.
During the treatment phase of AVANT patients were randomised to receive one of the following:
* Arm A: FOLFOX-4 for the first 24 weeks and observation for the remaining 24 weeks
* Arm B: Avastin (5 mg/kg every two weeks) in combination with FOLFOX-4 in the first 24 weeks and Avastin alone (7.5 mg/kg every three weeks) for the remaining 24 weeks
* Arm C: Avastin (7.5 mg/kg every three weeks) in combination with XELOX in the first 24 weeks and Avastin alone (7.5 mg/kg every three weeks) for the remaining 24 weeks
The primary endpoint of the study was disease-free survival in patients with stage III colon cancer. Secondary endpoints include overall survival and safety.
About the C-08 study
NSABP C-08 is a randomised phase III study designed to evaluate the use of Avastin plus chemotherapy (mFOLFOX-6) for the treatment of colon cancer as adjuvant therapy compared to chemotherapy alone for patients with early-stage colon cancer (high risk stage II and stage III). The study showed the addition of one year of Avastin to chemotherapy did not result in a statistically significant improvement in disease-free survival. NSABP C-08 included a comprehensive safety analysis that showed no new or unexpected safety findings related to Avastin in the study. (Wolmark et al. ASCO 2009).
About Avastin: Over 5 Years of Transforming Cancer Care
With the initial approval in the USA for advanced colorectal cancer in 2004, Avastin became the first anti-angiogenic therapy made widely available for the treatment of patients with an advanced cancer.
Today, Avastin is continuing to transform cancer care through its proven survival benefit (overall survival and/or progression free survival) across several types of cancer. Avastin is approved in the US and Europe for the treatment of advanced stages of colorectal cancer, breast cancer, non-small cell lung cancer and kidney cancer, and Avastin is also available in the US and 27 other countries for the treatment of patients with glioblastoma (a type of brain cancer). Avastin is the only anti-angiogenic therapy available for the treatment of these numerous advanced cancer types, which collectively cause over 2.5 million deaths each year.
Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today – over three quarters of a million patients have been treated with Avastin so far. A comprehensive clinical programme with more than 500 ongoing clinical trials is investigating the use of Avastin in over 50 tumour types (including colorectal, breast, non-small cell lung, brain, gastric, ovarian and others) and different settings (advanced or early stage disease).
About Avastin: Mode of Action
Avastin is an antibody that specifically binds and blocks the biological effects of VEGF (vascular endothelial growth factor). VEGF is the key driver of tumour angiogenesis – a fundamental process required for a tumour to grow and to spread (metastasise) to other parts of the body. Avastin’s precise mode of action allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments. Avastin helps to control tumour growth and extend survival with only a limited impact on the side effects of chemotherapy.
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.
SOURCE: F. Hoffmann-La Roche Ltd
Post Views: 35
Second phase III study does not meet primary endpoint
BASEL, SWITZERLAND | September 21, 2010 | Roche today announced the topline results of a second phase III trial evaluating the use of Avastin (bevacizumab) plus chemotherapy in the adjuvant treatment (immediately after surgery) of early-stage colon cancer. The trial compared the efficacy and safety of Avastin plus chemotherapy to chemotherapy alone. The study, known as AVANT, did not meet its primary endpoint of improving disease-free survival in stage III colon cancer. Adverse events were consistent with those previously observed in pivotal trials of Avastin across tumour types for approved indications. These results do not affect Avastin’s approved indications in advanced (metastatic) disease.
In line with the previously reported NSABP C-08 study results that also evaluated Avastin in the early-stage setting, the AVANT study shows that standard chemotherapy plus one year of Avastin is not effective in reducing the risk of relapses in early-stage colon cancer. Unlike the C-08 results, preliminary efficacy data from AVANT numerically favour chemotherapy alone (the control arm). Roche is evaluating the data from these two studies to help define the next steps for the ongoing Avastin adjuvant programme.
“While we originally hoped the significant survival benefit of Avastin seen in metastatic disease in colorectal cancer would be translated to the early setting, it is becoming increasingly clear that the effects of Avastin are different in the metastatic and early disease settings for patients with colon cancer.’’ said Hal Barron, M.D., Head of Global Product Development and Chief Medical Officer at Roche.
Data from the AVANT study will be submitted for presentation at a scientific congress in 2011.
About the AVANT study
AVANT is a randomised, three-arm phase III study in 3,451 patients evaluating Avastin in combination with either capecitabine plus oxaliplatin (XELOX) or fluorouracil/leucovorin with oxaliplatin (FOLFOX-4) versus FOLFOX-4 alone as adjuvant chemotherapy in patients who have undergone surgery for high-risk stage II and stage III colon cancer.
During the treatment phase of AVANT patients were randomised to receive one of the following:
* Arm A: FOLFOX-4 for the first 24 weeks and observation for the remaining 24 weeks
* Arm B: Avastin (5 mg/kg every two weeks) in combination with FOLFOX-4 in the first 24 weeks and Avastin alone (7.5 mg/kg every three weeks) for the remaining 24 weeks
* Arm C: Avastin (7.5 mg/kg every three weeks) in combination with XELOX in the first 24 weeks and Avastin alone (7.5 mg/kg every three weeks) for the remaining 24 weeks
The primary endpoint of the study was disease-free survival in patients with stage III colon cancer. Secondary endpoints include overall survival and safety.
About the C-08 study
NSABP C-08 is a randomised phase III study designed to evaluate the use of Avastin plus chemotherapy (mFOLFOX-6) for the treatment of colon cancer as adjuvant therapy compared to chemotherapy alone for patients with early-stage colon cancer (high risk stage II and stage III). The study showed the addition of one year of Avastin to chemotherapy did not result in a statistically significant improvement in disease-free survival. NSABP C-08 included a comprehensive safety analysis that showed no new or unexpected safety findings related to Avastin in the study. (Wolmark et al. ASCO 2009).
About Avastin: Over 5 Years of Transforming Cancer Care
With the initial approval in the USA for advanced colorectal cancer in 2004, Avastin became the first anti-angiogenic therapy made widely available for the treatment of patients with an advanced cancer.
Today, Avastin is continuing to transform cancer care through its proven survival benefit (overall survival and/or progression free survival) across several types of cancer. Avastin is approved in the US and Europe for the treatment of advanced stages of colorectal cancer, breast cancer, non-small cell lung cancer and kidney cancer, and Avastin is also available in the US and 27 other countries for the treatment of patients with glioblastoma (a type of brain cancer). Avastin is the only anti-angiogenic therapy available for the treatment of these numerous advanced cancer types, which collectively cause over 2.5 million deaths each year.
Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today – over three quarters of a million patients have been treated with Avastin so far. A comprehensive clinical programme with more than 500 ongoing clinical trials is investigating the use of Avastin in over 50 tumour types (including colorectal, breast, non-small cell lung, brain, gastric, ovarian and others) and different settings (advanced or early stage disease).
About Avastin: Mode of Action
Avastin is an antibody that specifically binds and blocks the biological effects of VEGF (vascular endothelial growth factor). VEGF is the key driver of tumour angiogenesis – a fundamental process required for a tumour to grow and to spread (metastasise) to other parts of the body. Avastin’s precise mode of action allows it to be combined effectively with a broad range of chemotherapies and other anti-cancer treatments. Avastin helps to control tumour growth and extend survival with only a limited impact on the side effects of chemotherapy.
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.
SOURCE: F. Hoffmann-La Roche Ltd
Post Views: 35
