Lani
02-02-2011, 01:54 AM
even though most of the risks are quite small** and some subgroups of breast cancer may benefit
substantially. If it didn't cost so much, I doubt they would be as concerned. It is necessary to test it in a large enough number of people to be able to "tease out" the subgroup in which it is so effective that the risk/benefit ratio is of no question
another comment: No trial of avastin without chemo ie, with only another targeted agent was
included and** the adverse events occurred with the higher (double) dose rather than the lower one:
People who took Roche's popular cancer drug Avastin in combination with chemotherapy had a 46 percent higher risk of dying from drug-related side effects than people who got chemotherapy alone, researchers said on Tuesday.
But they said the overall rate of deaths caused by Avastin when used with chemotherapy was still low at 2.5 percent, and that the benefits need to be weighed against the risks.
Roche's Genentech unit said the analysis, published in the Journal of the American Medical Association, includes data on cancers in which the drug is not approved and should not be used.
Dr. Shenhong Wu of Stony Brook University School of Medicine in New York and colleagues pooled data from 16 previously published trials of patients with different types of cancer and found the rate of deaths was 1.5 times higher among people who took Avastin, or bevacizumab, plus chemotherapy compared with those who got chemotherapy alone.
"We discovered the use of bevacizumab in combination with other chemotherapy or biological therapy increased the risk of treatment-related mortality by 46 percent," Wu said in a statement.
Avastin, the world's best-selling cancer medicine with annual sales of $6 billion, has been approved for fighting several different cancers, including certain types of lung cancer, advanced colorectal and kidney cancers.
It had been approved to treat breast cancer, but it failed to help breast cancer patients live longer in four clinical trials, and U.S. regulators in December rescinded its approval in breast cancer.
Avastin blocks vascular endothelial growth factor, or VEGF, which is needed to form blood vessels to feed tumors but also needed for normal blood vessel growth.
HEMORRHAGING, BLOOD CLOTS
Many of the side effects involved bleeding, including hemorrhages, low white blood cell count, holes in the stomach and intestines and blood clots in the lungs.
The team said the overall rate of deaths caused by the drug was 2.5 percent, but the risks varied significantly depending on which chemotherapy drug was used.
Because the absolute risk of treatment-related death appears low, the team said use of Avastin should be considered in the context of its overall survival benefits.
Roche said the data used in the analysis is not new and included data on cancers for which the drug is not approved, including squamous cell, non-small cell lung, prostate and pancreatic cancers.
"Avastin does have serious risks within cancer care which are clearly outlined on its label," Charlotte Arnold, a spokeswoman for Roche's Genentech unit, said in a telephone interview.
She said in the indications in which it is approved, the risk-benefit profile is considered favorable
Dr. Roman Perez-Soler of Montefiore-Einstein Center for Cancer Care in New York who has seen the study but was not involved with the analysis said all cancer drugs have potentially fatal side effects, including chemotherapy.
"We have to put everything in perspective," Perez-Soler said in a telephone interview.
He said the overall increased risk of taking Avastin should be weighed by the chance that it could extend the lives of gravely ill cancer patients.
"I think we should know that it may happen and be careful in selecting the patients in which we give the drug," Perez-Solar said. "That is the positive aspect of the article."
^^^^^
Cancer drug used in combination with other therapies associated with increased risk of death
An analysis of previous studies indicates that compared with chemotherapy alone, use of the cancer drug bevacizumab in combination with chemotherapy or biological therapy is associated with an increased risk of treatment-related death, according to an article in the February 2 issue of JAMA.
A fatal adverse event (FAE) is defined as a death caused in all likelihood by a drug and is a major cause of fatality in the United States. Bevacizumab was approved in combination with chemotherapy for treating many types of advanced cancer, including colorectal cancer, non-small cell lung cancer, breast cancer, and renal cell carcinoma. "Even though a number of FAEs have been reported in patients treated with bevacizumab, its role in the development of these fatal events has not been definitively established. Data across bevacizumab trials reveal conflicting results regarding its associations with FAEs," according to background information in the article.
Vishal Ranpura, M.D., of Stony Brook University Medical Center, Stony Brook, N.Y., and colleagues conducted a review and meta-analysis of published randomized controlled trials (RCTs) to determine whether bevacizumab is associated with increased rates of FAEs in patients with cancer. The researchers identified and included 16 RCTs in the analysis. These RCTs included a total of 10,217 patients with a variety of advanced solid tumors. Eligible studies included RCTs in which bevacizumab in combination with chemotherapy or biological therapy was compared with chemotherapy or biological therapy alone.
The overall incidence of FAEs with bevacizumab was 2.5 percent. Compared with chemotherapy alone, the addition of bevacizumab was associated with a 1.5 times increased risk of FAEs. This association varied significantly with chemotherapeutic agents but not with tumor types or bevacizumab doses. Bevacizumab was associated with a 3.5 times increased risk of FAEs in patients receiving taxanes or platinum agents (3.3 percent vs. 1.0 percent), but was not associated with increased risk of FAEs when used in conjunction with other agents.
Common specific causes of FAEs included hemorrhage (23.5 percent), neutropenia (a blood disorder; 12.2 percent), gastrointestinal tract perforation (7.1 percent), pulmonary embolism (5.1 percent), and cerebrovascular accident (5.1 percent). Pulmonary (14/23) and gastrointestinal hemorrhage (6/23) accounted for most fatal bleeding events.
The authors write that given the absolute risk of treatment-related mortality appears low, the use of bevacizumab should be considered in the context of overall survival benefits. They add that because bevacizumab is increasingly used in cancer patients, it is particularly important for all health care practitioners and patients to understand and recognize the risk of treatment-related mortality and to monitor closely to identify and treat serious adverse effects.
(JAMA. 2011;305[5]:487-494. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Bevacizumab Treatment for Solid Tumors
In an accompanying editorial, Daniel F. Hayes, M.D., of the University of Michigan Comprehensive Cancer Center, Ann Arbor, Mich., writes that careful review of response rates to bevacizumab suggest that bevacizumab works well, but only in selected patients.
"Is bevacizumab a boon or a bust? The jury is still out. Although bevacizumab has benefit, it is currently not possible to determine in whom or for how long. Thus, oncologists are forced to dilute the potential effects of bevacizumab by exposing all treated patients, and society, to enormous costs and occasional life-threatening toxic effects. These unfortunate circumstances are sad for those who pay the bills— and sadder for patients with solid tumors."
substantially. If it didn't cost so much, I doubt they would be as concerned. It is necessary to test it in a large enough number of people to be able to "tease out" the subgroup in which it is so effective that the risk/benefit ratio is of no question
another comment: No trial of avastin without chemo ie, with only another targeted agent was
included and** the adverse events occurred with the higher (double) dose rather than the lower one:
People who took Roche's popular cancer drug Avastin in combination with chemotherapy had a 46 percent higher risk of dying from drug-related side effects than people who got chemotherapy alone, researchers said on Tuesday.
But they said the overall rate of deaths caused by Avastin when used with chemotherapy was still low at 2.5 percent, and that the benefits need to be weighed against the risks.
Roche's Genentech unit said the analysis, published in the Journal of the American Medical Association, includes data on cancers in which the drug is not approved and should not be used.
Dr. Shenhong Wu of Stony Brook University School of Medicine in New York and colleagues pooled data from 16 previously published trials of patients with different types of cancer and found the rate of deaths was 1.5 times higher among people who took Avastin, or bevacizumab, plus chemotherapy compared with those who got chemotherapy alone.
"We discovered the use of bevacizumab in combination with other chemotherapy or biological therapy increased the risk of treatment-related mortality by 46 percent," Wu said in a statement.
Avastin, the world's best-selling cancer medicine with annual sales of $6 billion, has been approved for fighting several different cancers, including certain types of lung cancer, advanced colorectal and kidney cancers.
It had been approved to treat breast cancer, but it failed to help breast cancer patients live longer in four clinical trials, and U.S. regulators in December rescinded its approval in breast cancer.
Avastin blocks vascular endothelial growth factor, or VEGF, which is needed to form blood vessels to feed tumors but also needed for normal blood vessel growth.
HEMORRHAGING, BLOOD CLOTS
Many of the side effects involved bleeding, including hemorrhages, low white blood cell count, holes in the stomach and intestines and blood clots in the lungs.
The team said the overall rate of deaths caused by the drug was 2.5 percent, but the risks varied significantly depending on which chemotherapy drug was used.
Because the absolute risk of treatment-related death appears low, the team said use of Avastin should be considered in the context of its overall survival benefits.
Roche said the data used in the analysis is not new and included data on cancers for which the drug is not approved, including squamous cell, non-small cell lung, prostate and pancreatic cancers.
"Avastin does have serious risks within cancer care which are clearly outlined on its label," Charlotte Arnold, a spokeswoman for Roche's Genentech unit, said in a telephone interview.
She said in the indications in which it is approved, the risk-benefit profile is considered favorable
Dr. Roman Perez-Soler of Montefiore-Einstein Center for Cancer Care in New York who has seen the study but was not involved with the analysis said all cancer drugs have potentially fatal side effects, including chemotherapy.
"We have to put everything in perspective," Perez-Soler said in a telephone interview.
He said the overall increased risk of taking Avastin should be weighed by the chance that it could extend the lives of gravely ill cancer patients.
"I think we should know that it may happen and be careful in selecting the patients in which we give the drug," Perez-Solar said. "That is the positive aspect of the article."
^^^^^
Cancer drug used in combination with other therapies associated with increased risk of death
An analysis of previous studies indicates that compared with chemotherapy alone, use of the cancer drug bevacizumab in combination with chemotherapy or biological therapy is associated with an increased risk of treatment-related death, according to an article in the February 2 issue of JAMA.
A fatal adverse event (FAE) is defined as a death caused in all likelihood by a drug and is a major cause of fatality in the United States. Bevacizumab was approved in combination with chemotherapy for treating many types of advanced cancer, including colorectal cancer, non-small cell lung cancer, breast cancer, and renal cell carcinoma. "Even though a number of FAEs have been reported in patients treated with bevacizumab, its role in the development of these fatal events has not been definitively established. Data across bevacizumab trials reveal conflicting results regarding its associations with FAEs," according to background information in the article.
Vishal Ranpura, M.D., of Stony Brook University Medical Center, Stony Brook, N.Y., and colleagues conducted a review and meta-analysis of published randomized controlled trials (RCTs) to determine whether bevacizumab is associated with increased rates of FAEs in patients with cancer. The researchers identified and included 16 RCTs in the analysis. These RCTs included a total of 10,217 patients with a variety of advanced solid tumors. Eligible studies included RCTs in which bevacizumab in combination with chemotherapy or biological therapy was compared with chemotherapy or biological therapy alone.
The overall incidence of FAEs with bevacizumab was 2.5 percent. Compared with chemotherapy alone, the addition of bevacizumab was associated with a 1.5 times increased risk of FAEs. This association varied significantly with chemotherapeutic agents but not with tumor types or bevacizumab doses. Bevacizumab was associated with a 3.5 times increased risk of FAEs in patients receiving taxanes or platinum agents (3.3 percent vs. 1.0 percent), but was not associated with increased risk of FAEs when used in conjunction with other agents.
Common specific causes of FAEs included hemorrhage (23.5 percent), neutropenia (a blood disorder; 12.2 percent), gastrointestinal tract perforation (7.1 percent), pulmonary embolism (5.1 percent), and cerebrovascular accident (5.1 percent). Pulmonary (14/23) and gastrointestinal hemorrhage (6/23) accounted for most fatal bleeding events.
The authors write that given the absolute risk of treatment-related mortality appears low, the use of bevacizumab should be considered in the context of overall survival benefits. They add that because bevacizumab is increasingly used in cancer patients, it is particularly important for all health care practitioners and patients to understand and recognize the risk of treatment-related mortality and to monitor closely to identify and treat serious adverse effects.
(JAMA. 2011;305[5]:487-494. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Bevacizumab Treatment for Solid Tumors
In an accompanying editorial, Daniel F. Hayes, M.D., of the University of Michigan Comprehensive Cancer Center, Ann Arbor, Mich., writes that careful review of response rates to bevacizumab suggest that bevacizumab works well, but only in selected patients.
"Is bevacizumab a boon or a bust? The jury is still out. Although bevacizumab has benefit, it is currently not possible to determine in whom or for how long. Thus, oncologists are forced to dilute the potential effects of bevacizumab by exposing all treated patients, and society, to enormous costs and occasional life-threatening toxic effects. These unfortunate circumstances are sad for those who pay the bills— and sadder for patients with solid tumors."