Monday, July 26, 2010
Wednesday, July 21, 2010
Avastin: Advisory panel recommends FDA to remove advanced breast cancer indication
GAITHERSBURG, Md. – In a vote of 12 to 1 a recommendation has been issued by the Oncologic Drugs Advisory Committee advisory panel that the FDA remove the advanced breast cancer indication from Avastin (bevacizumab), after two large clinical trials failed to demonstrate a clinically significant benefit of the drug, which is associated with serious side effects. When used in combination with standard chemotherapy, Avastin did not extend progression-free survival (PFS) long enough to be clinically significant in HER2-negative, metastatic breast cancer.
In 2008, the FDA granted special, fast-track approval to Genentech, manufacturer of Avastin, to begin marketing the drug for patients with metastatic breast cancer in combination with the chemotherapy agent paclitaxel. This "accelerated" approval was based on positive early findings from a large Genentech-sponsored clinical trial that found Avastin added 5.5 months PFS vs. paclitaxel alone. However, the data from two new clinical trials (AVADO, RIBBON-1) of almost 2,000 breast cancer patients that Genentech submitted to move from accelerated approval to standard approval failed to demonstrate the PFS to the extent seen in the earlier study.* The PFS in the two trials ranged from a little less than a month, to just under three months. The results failed to demonstrate that the benefits of using Avastin outweigh the potential risks, which include a small risk of death, bleeding, febrile neutropenia and hypertension.
Genentech argued that even small gains in progression-free survival are clinically meaningful and that additional weeks where tumors don't worsen translate to improved quality of life.
The FDA usually follows the advice of its advisory committee, and if they do this time, Avastin would still be approved to treat lung, kidney, and colon cancer. Avastin is also used treat recurrent glioblastoma under accelerated approval. The FDA will make a decision by September 17, 2010.
Source
FDA Panel Nixes Bevacizumab for Breast Cancer. By Emily P. Walker, Washington Correspondent, MedPage Today Published: July 20, 2010. Available at http://www.medpagetoday.com/HematologyOncology/BreastCancer/21276?utm_content=Group_&utm_medium=email&impressionId=&utm_campaign=DailyHeadlines&utm_source=mSpoke&userid= Accessed July 21, 2010.
In 2008, the FDA granted special, fast-track approval to Genentech, manufacturer of Avastin, to begin marketing the drug for patients with metastatic breast cancer in combination with the chemotherapy agent paclitaxel. This "accelerated" approval was based on positive early findings from a large Genentech-sponsored clinical trial that found Avastin added 5.5 months PFS vs. paclitaxel alone. However, the data from two new clinical trials (AVADO, RIBBON-1) of almost 2,000 breast cancer patients that Genentech submitted to move from accelerated approval to standard approval failed to demonstrate the PFS to the extent seen in the earlier study.* The PFS in the two trials ranged from a little less than a month, to just under three months. The results failed to demonstrate that the benefits of using Avastin outweigh the potential risks, which include a small risk of death, bleeding, febrile neutropenia and hypertension.
"Survival trumps everything, and we haven't shown a survival benefit here"
- Ronald Richardson, MD, a medical oncologist at the Mayo Clinic
Genentech argued that even small gains in progression-free survival are clinically meaningful and that additional weeks where tumors don't worsen translate to improved quality of life.
The FDA usually follows the advice of its advisory committee, and if they do this time, Avastin would still be approved to treat lung, kidney, and colon cancer. Avastin is also used treat recurrent glioblastoma under accelerated approval. The FDA will make a decision by September 17, 2010.
*For details of the studies see Avastin did not improve progression-free survival in patients with breast cancer. Available at http://medwritehealthcarecommunications.blogspot.com/2010/07/avastin-did-not-improve-progression.html. Posted July 19, 2010.
Source
FDA Panel Nixes Bevacizumab for Breast Cancer. By Emily P. Walker, Washington Correspondent, MedPage Today Published: July 20, 2010. Available at http://www.medpagetoday.com/HematologyOncology/BreastCancer/21276?utm_content=Group_&utm_medium=email&impressionId=&utm_campaign=DailyHeadlines&utm_source=mSpoke&userid= Accessed July 21, 2010.
Monday, July 19, 2010
Avastin did not improve progression-free survival in patients with breast cancer
Two new studies demonstrated that Avastin (bevacizumab), in combination with chemotherapy did not extend progression free survival (PFS) in patients with advanced breast cancer to the same levels observed in a previous trial used to garner approval of the drug in this indication in 2008. The FDA approved Avastin for treatment of breast cancer was based on results from the E2100 clinical trial, which demonstrated that Avastin in combination with paclitaxel slowed the spread of breast cancer and extended PFS by 5.5 months vs. paclitaxel alone.[1-2]
Data from two post-approval trials told a different story. A first, the AVADO clinical trial involving 736 patients with locally recurrent or metastatic HER2-negative breast cancer who had not previously received chemotherapy for their disease showed that a high dose of Avastin used in combination with docetaxel extended PFS by 0.9 months vs. docetaxel alone. Patients receiving a lower dose of Avastin had PFS extended by 0.8 months.[3]
A second post-approval trial, RIBBON-1 study involving 1237 women with locally recurrent or metastatic HER-2 negative breast cancer who had not received prior treatment for the disease demonstrated that Avastin in combination with taxane or anthracycline-based chemotherapies extended PFS by 1.2 months vs. chemotherapy alone. Patients receiving Avastin in combination with Xeloda (capecitabine) lived 2.9 months longer than patients receiving chemotherapy alone.[4]
Currently, Avastin is indicated for the use in: (1) first-line treatment of a subgroup of women with metastatic breast cancer known as HER2-negative breast cancer, in combination with the chemotherapy drug docetaxel; and (2) first-line treatment of HER2-negative metastatic breast cancer in combination with one of two classes of chemotherapy drugs, known as taxanes and anthracyclines, or with the chemotherapy drug, capecitabine. FDA approval is pending of additional indication for the treatment, in combination with the chemotherapy drug paclitaxel, of patients who have not received chemotherapy for their locally recurrent or metastatic HER2 negative breast cancer. The FDA may ultimately decide to withdraw its approval for Avastin based on results from the post-approval trials.
References:
1. FDA staff release review of Roche's Avastin in breast cancer. First Word. Light Edition. July 16, 2010. Available at http://www.firstwordplus.com/Fws.do?articleid=F731F4EE99584F0FB11A106C99246301 Accessed July 19, 2010.
2. July 20, 2010: Oncologic Drugs Advisory Committee Meeting Announcement. FDA U.S. Food and Drug Administration. Available at http://www.fda.gov/AdvisoryCommittees/Calendar/ucm213724.htm Accessed July 19, 2010.
3. Miles D, Chan A, G. Romieu G, et al. Randomized, double-blind, placebo-controlled, phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. J Clin Oncol 26: 2008 (May 20 suppl; abstr LBA1011). Available at http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=55&abstractID=34482 Accessed July 19, 2010.
4. Robert NJ, Dieras V, J. Glaspy J, et al. RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab (B) for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer (MBC). J Clin Oncol 27:15s, 2009 (suppl; abstr 1005). Available at http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=34532 Accessed July 19, 2010.
Data from two post-approval trials told a different story. A first, the AVADO clinical trial involving 736 patients with locally recurrent or metastatic HER2-negative breast cancer who had not previously received chemotherapy for their disease showed that a high dose of Avastin used in combination with docetaxel extended PFS by 0.9 months vs. docetaxel alone. Patients receiving a lower dose of Avastin had PFS extended by 0.8 months.[3]
A second post-approval trial, RIBBON-1 study involving 1237 women with locally recurrent or metastatic HER-2 negative breast cancer who had not received prior treatment for the disease demonstrated that Avastin in combination with taxane or anthracycline-based chemotherapies extended PFS by 1.2 months vs. chemotherapy alone. Patients receiving Avastin in combination with Xeloda (capecitabine) lived 2.9 months longer than patients receiving chemotherapy alone.[4]
Currently, Avastin is indicated for the use in: (1) first-line treatment of a subgroup of women with metastatic breast cancer known as HER2-negative breast cancer, in combination with the chemotherapy drug docetaxel; and (2) first-line treatment of HER2-negative metastatic breast cancer in combination with one of two classes of chemotherapy drugs, known as taxanes and anthracyclines, or with the chemotherapy drug, capecitabine. FDA approval is pending of additional indication for the treatment, in combination with the chemotherapy drug paclitaxel, of patients who have not received chemotherapy for their locally recurrent or metastatic HER2 negative breast cancer. The FDA may ultimately decide to withdraw its approval for Avastin based on results from the post-approval trials.
References:
1. FDA staff release review of Roche's Avastin in breast cancer. First Word. Light Edition. July 16, 2010. Available at http://www.firstwordplus.com/Fws.do?articleid=F731F4EE99584F0FB11A106C99246301 Accessed July 19, 2010.
2. July 20, 2010: Oncologic Drugs Advisory Committee Meeting Announcement. FDA U.S. Food and Drug Administration. Available at http://www.fda.gov/AdvisoryCommittees/Calendar/ucm213724.htm Accessed July 19, 2010.
3. Miles D, Chan A, G. Romieu G, et al. Randomized, double-blind, placebo-controlled, phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. J Clin Oncol 26: 2008 (May 20 suppl; abstr LBA1011). Available at http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=55&abstractID=34482 Accessed July 19, 2010.
4. Robert NJ, Dieras V, J. Glaspy J, et al. RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab (B) for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer (MBC). J Clin Oncol 27:15s, 2009 (suppl; abstr 1005). Available at http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=34532 Accessed July 19, 2010.
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