Richard Hyer

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.

CHICAGO – Denosumab, a drug newly approved for prevention of skeletal-related adverse events in cancer patients with bone metastases from solid tumors, is not cost effective when compared with zoledronic acid in patients with breast or prostate cancers, according to a pair of pharmacoeconomic analyses.

A review of data from a key phase III trial in 2,046 patients with metastatic breast cancer found the cost per quality-adjusted life-year (QALY) gained with denosumab (Xgeva) was $643,726 when compared with zoledronic acid (Zometa), John A. Carter and his coinvestigators reported in a poster presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

This ratio is far higher than the $50,000 to $100,000 that is considered to be good value for a medical intervention, they said.

A related study in castration-resistant prostate cancer metastatic to the bone found even more substantial cost differentials. The resultant cost per QALY for denosumab would be approximately $1.25 million in this setting, reported Sonya H. Snedecor, Ph.D., and her coauthors in the second poster.

In both studies, investigators attributed the high cost per QALY to the higher drug acquisition cost of denosumab combined with limited added prevention of skeletal-related events (SREs) and a lack of overall survival or disease progression benefits for denosumab vs. zoledronic acid.

"What we found [in the prostate cancer study] is that there were very little gains in quality-adjusted life-years with the use of denosumab – very, very minuscule, about five per thousandths of a year," senior author Marc Botteman said in an interview.

"So you spend $5,000 to get that five per thousandths of a year, and that leads to a cost-effectiveness ratio of $1.25 million, which is way, way, way higher than what people typically consider to be acceptable in general, or in oncology," said Mr. Botteman, cofounder and managing partner of Pharmerit North America, a health economics and outcomes research firm that conducted the analyses. Both studies were sponsored by Novartis, maker of zoledronic acid.

For the two studies, Pharmerit developed a Markov model based on trial data to estimate survival, QALYs, number and costs of skeletal-related events, and drug and administration costs. QALYs were estimated by assigning utilities to four health states: prior to skeletal-related event; the event; post-event; and death.

"Quality-adjusted life-years are a metric used by health economists to estimate the value of treatment in terms of clinical benefits. The index combines survival and quality of life during that survival," Mr. Botteman said.

Denosumab maker Amgen responded to a request for a response with an e-mailed statement that challenged the models’ use of event rates based on clinical trials rather than event rates observed in real-world clinical practice. Amgen also contended that the models underestimate the value of denosumab "by attributing lower costs to SREs than those seen in the real world," and it criticized the limited time frames used in the models.

"Economic models should extend far enough into the future to capture the major health and economic outcomes. By truncating the modeling time frame the value of preventing/delaying SREs will also be reduced," it said.

The statement also touted denosumab’s superiority in preventing SREs in patients with advanced solid tumors, and contended that this "could result in direct cost offsets due to reduced incidence of SREs and related medical costs."

"Amgen stands by the value of Xgeva for patients, health care providers, and payers," the statement concluded, citing denosumab’s safety profile, subcutaneous administration, and other attributes not covered by Pharmerit’s model.

The breast cancer poster used data from a phase III trial that contributed to the Food and Drug Administration’s decision in November 2010 to approve denusumab for the prevention of SREs in patients with bone metastases from solid tumors. The trial found denosumab to be superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer that had spread to the bone. Both drugs showed similar results in overall survival, disease progression, and serious adverse events (J. Clin. Onc. 2010;28:5132-39).

The poster reported the cost of a denusumab injection to be nearly twice that of zoledronic acid, at $1,650 vs. $887. Compared with the older drug, denosumab was found to result in fewer SREs and resultant costs, and slightly more QALYs. It was associated with higher drug-related costs, however.

As a result, total discounted costs were higher for denosumab by an addition of $6,884 per patient over the period of analysis. The cost per QALY gained was $644,000 when excluding SREs and $613,000 per QALY when including SREs, the authors wrote.

Discussing the poster at the ASCO meeting, Dr. Thomas J. Smith of the Massey Cancer Center at Virginia Commonwealth University, Richmond, said it "raises some significant concern about money-driven value in metastatic breast cancer treatment."

Dr. Smith said that the study raises questions about physicians’ ability to negotiate prices, and how to use these data in making decisions. "I can tell you that at most hospitals, most P&T [pharmacy and therapeutics] committees have wrestled exactly with this, ... and where does this fit in pathway-driven managed care, where you get a fixed amount to take care of these patients?" he said.

That the analysis was funded by the maker of zoledronic acid also was a concern. "So I would wait to draw conclusions until this has been through peer review," Dr. Smith said.

The prostate cancer study found that denosumab marginally improved quality of life (+0.0043 QALYs) relative to zoledronic acid, and reduced costs of SREs by $1,924 based on a calculation that these would cost $7,604 with denosumab vs. $9,528 with zoledronic acid over 27 months of treatment. To achieve those benefits, the patient would have to invest more than $7,313 in additional drug costs with denosumab, and thus incur a net cost of $5,390 over 27 months, according to the study.

Novartis, the maker of zoledronic acid, sponsored both studies. Mr. Carter and Dr. Snedecor disclosed consultant or advisory roles with Novartis. One of their coauthors was a Novartis employee with stock ownership. Mr. Botteman disclosed consultant or advisory roles with Pharmerit. Dr. Smith disclosed research funding from the American Cancer Society and the National Cancer Institute.

CHICAGO – Denosumab, a drug newly approved for prevention of skeletal-related adverse events in cancer patients with bone metastases from solid tumors, is not cost effective when compared with zoledronic acid in patients with breast or prostate cancers, according to a pair of pharmacoeconomic analyses.

A review of data from a key phase III trial in 2,046 patients with metastatic breast cancer found the cost per quality-adjusted life-year (QALY) gained with denosumab (Xgeva) was $643,726 when compared with zoledronic acid (Zometa), John A. Carter and his coinvestigators reported in a poster presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

This ratio is far higher than the $50,000 to $100,000 that is considered to be good value for a medical intervention, they said.

A related study in castration-resistant prostate cancer metastatic to the bone found even more substantial cost differentials. The resultant cost per QALY for denosumab would be approximately $1.25 million in this setting, reported Sonya H. Snedecor, Ph.D., and her coauthors in the second poster.

In both studies, investigators attributed the high cost per QALY to the higher drug acquisition cost of denosumab combined with limited added prevention of skeletal-related events (SREs) and a lack of overall survival or disease progression benefits for denosumab vs. zoledronic acid.

"What we found [in the prostate cancer study] is that there were very little gains in quality-adjusted life-years with the use of denosumab – very, very minuscule, about five per thousandths of a year," senior author Marc Botteman said in an interview.

"So you spend $5,000 to get that five per thousandths of a year, and that leads to a cost-effectiveness ratio of $1.25 million, which is way, way, way higher than what people typically consider to be acceptable in general, or in oncology," said Mr. Botteman, cofounder and managing partner of Pharmerit North America, a health economics and outcomes research firm that conducted the analyses. Both studies were sponsored by Novartis, maker of zoledronic acid.

For the two studies, Pharmerit developed a Markov model based on trial data to estimate survival, QALYs, number and costs of skeletal-related events, and drug and administration costs. QALYs were estimated by assigning utilities to four health states: prior to skeletal-related event; the event; post-event; and death.

"Quality-adjusted life-years are a metric used by health economists to estimate the value of treatment in terms of clinical benefits. The index combines survival and quality of life during that survival," Mr. Botteman said.

Denosumab maker Amgen responded to a request for a response with an e-mailed statement that challenged the models’ use of event rates based on clinical trials rather than event rates observed in real-world clinical practice. Amgen also contended that the models underestimate the value of denosumab "by attributing lower costs to SREs than those seen in the real world," and it criticized the limited time frames used in the models.

"Economic models should extend far enough into the future to capture the major health and economic outcomes. By truncating the modeling time frame the value of preventing/delaying SREs will also be reduced," it said.

The statement also touted denosumab’s superiority in preventing SREs in patients with advanced solid tumors, and contended that this "could result in direct cost offsets due to reduced incidence of SREs and related medical costs."

"Amgen stands by the value of Xgeva for patients, health care providers, and payers," the statement concluded, citing denosumab’s safety profile, subcutaneous administration, and other attributes not covered by Pharmerit’s model.

The breast cancer poster used data from a phase III trial that contributed to the Food and Drug Administration’s decision in November 2010 to approve denusumab for the prevention of SREs in patients with bone metastases from solid tumors. The trial found denosumab to be superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer that had spread to the bone. Both drugs showed similar results in overall survival, disease progression, and serious adverse events (J. Clin. Onc. 2010;28:5132-39).

The poster reported the cost of a denusumab injection to be nearly twice that of zoledronic acid, at $1,650 vs. $887. Compared with the older drug, denosumab was found to result in fewer SREs and resultant costs, and slightly more QALYs. It was associated with higher drug-related costs, however.

As a result, total discounted costs were higher for denosumab by an addition of $6,884 per patient over the period of analysis. The cost per QALY gained was $644,000 when excluding SREs and $613,000 per QALY when including SREs, the authors wrote.

Discussing the poster at the ASCO meeting, Dr. Thomas J. Smith of the Massey Cancer Center at Virginia Commonwealth University, Richmond, said it "raises some significant concern about money-driven value in metastatic breast cancer treatment."

Dr. Smith said that the study raises questions about physicians’ ability to negotiate prices, and how to use these data in making decisions. "I can tell you that at most hospitals, most P&T [pharmacy and therapeutics] committees have wrestled exactly with this, ... and where does this fit in pathway-driven managed care, where you get a fixed amount to take care of these patients?" he said.

That the analysis was funded by the maker of zoledronic acid also was a concern. "So I would wait to draw conclusions until this has been through peer review," Dr. Smith said.

The prostate cancer study found that denosumab marginally improved quality of life (+0.0043 QALYs) relative to zoledronic acid, and reduced costs of SREs by $1,924 based on a calculation that these would cost $7,604 with denosumab vs. $9,528 with zoledronic acid over 27 months of treatment. To achieve those benefits, the patient would have to invest more than $7,313 in additional drug costs with denosumab, and thus incur a net cost of $5,390 over 27 months, according to the study.

Novartis, the maker of zoledronic acid, sponsored both studies. Mr. Carter and Dr. Snedecor disclosed consultant or advisory roles with Novartis. One of their coauthors was a Novartis employee with stock ownership. Mr. Botteman disclosed consultant or advisory roles with Pharmerit. Dr. Smith disclosed research funding from the American Cancer Society and the National Cancer Institute.

CHICAGO – Denosumab, a drug newly approved for prevention of skeletal-related adverse events in cancer patients with bone metastases from solid tumors, is not cost effective when compared with zoledronic acid in patients with breast or prostate cancers, according to a pair of pharmacoeconomic analyses.

A review of data from a key phase III trial in 2,046 patients with metastatic breast cancer found the cost per quality-adjusted life-year (QALY) gained with denosumab (Xgeva) was $643,726 when compared with zoledronic acid (Zometa), John A. Carter and his coinvestigators reported in a poster presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

This ratio is far higher than the $50,000 to $100,000 that is considered to be good value for a medical intervention, they said.

A related study in castration-resistant prostate cancer metastatic to the bone found even more substantial cost differentials. The resultant cost per QALY for denosumab would be approximately $1.25 million in this setting, reported Sonya H. Snedecor, Ph.D., and her coauthors in the second poster.

In both studies, investigators attributed the high cost per QALY to the higher drug acquisition cost of denosumab combined with limited added prevention of skeletal-related events (SREs) and a lack of overall survival or disease progression benefits for denosumab vs. zoledronic acid.

"What we found [in the prostate cancer study] is that there were very little gains in quality-adjusted life-years with the use of denosumab – very, very minuscule, about five per thousandths of a year," senior author Marc Botteman said in an interview.

"So you spend $5,000 to get that five per thousandths of a year, and that leads to a cost-effectiveness ratio of $1.25 million, which is way, way, way higher than what people typically consider to be acceptable in general, or in oncology," said Mr. Botteman, cofounder and managing partner of Pharmerit North America, a health economics and outcomes research firm that conducted the analyses. Both studies were sponsored by Novartis, maker of zoledronic acid.

For the two studies, Pharmerit developed a Markov model based on trial data to estimate survival, QALYs, number and costs of skeletal-related events, and drug and administration costs. QALYs were estimated by assigning utilities to four health states: prior to skeletal-related event; the event; post-event; and death.

"Quality-adjusted life-years are a metric used by health economists to estimate the value of treatment in terms of clinical benefits. The index combines survival and quality of life during that survival," Mr. Botteman said.

Denosumab maker Amgen responded to a request for a response with an e-mailed statement that challenged the models’ use of event rates based on clinical trials rather than event rates observed in real-world clinical practice. Amgen also contended that the models underestimate the value of denosumab "by attributing lower costs to SREs than those seen in the real world," and it criticized the limited time frames used in the models.

"Economic models should extend far enough into the future to capture the major health and economic outcomes. By truncating the modeling time frame the value of preventing/delaying SREs will also be reduced," it said.

The statement also touted denosumab’s superiority in preventing SREs in patients with advanced solid tumors, and contended that this "could result in direct cost offsets due to reduced incidence of SREs and related medical costs."

"Amgen stands by the value of Xgeva for patients, health care providers, and payers," the statement concluded, citing denosumab’s safety profile, subcutaneous administration, and other attributes not covered by Pharmerit’s model.

The breast cancer poster used data from a phase III trial that contributed to the Food and Drug Administration’s decision in November 2010 to approve denusumab for the prevention of SREs in patients with bone metastases from solid tumors. The trial found denosumab to be superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer that had spread to the bone. Both drugs showed similar results in overall survival, disease progression, and serious adverse events (J. Clin. Onc. 2010;28:5132-39).

The poster reported the cost of a denusumab injection to be nearly twice that of zoledronic acid, at $1,650 vs. $887. Compared with the older drug, denosumab was found to result in fewer SREs and resultant costs, and slightly more QALYs. It was associated with higher drug-related costs, however.

As a result, total discounted costs were higher for denosumab by an addition of $6,884 per patient over the period of analysis. The cost per QALY gained was $644,000 when excluding SREs and $613,000 per QALY when including SREs, the authors wrote.

Discussing the poster at the ASCO meeting, Dr. Thomas J. Smith of the Massey Cancer Center at Virginia Commonwealth University, Richmond, said it "raises some significant concern about money-driven value in metastatic breast cancer treatment."

Dr. Smith said that the study raises questions about physicians’ ability to negotiate prices, and how to use these data in making decisions. "I can tell you that at most hospitals, most P&T [pharmacy and therapeutics] committees have wrestled exactly with this, ... and where does this fit in pathway-driven managed care, where you get a fixed amount to take care of these patients?" he said.

That the analysis was funded by the maker of zoledronic acid also was a concern. "So I would wait to draw conclusions until this has been through peer review," Dr. Smith said.

The prostate cancer study found that denosumab marginally improved quality of life (+0.0043 QALYs) relative to zoledronic acid, and reduced costs of SREs by $1,924 based on a calculation that these would cost $7,604 with denosumab vs. $9,528 with zoledronic acid over 27 months of treatment. To achieve those benefits, the patient would have to invest more than $7,313 in additional drug costs with denosumab, and thus incur a net cost of $5,390 over 27 months, according to the study.

Novartis, the maker of zoledronic acid, sponsored both studies. Mr. Carter and Dr. Snedecor disclosed consultant or advisory roles with Novartis. One of their coauthors was a Novartis employee with stock ownership. Mr. Botteman disclosed consultant or advisory roles with Pharmerit. Dr. Smith disclosed research funding from the American Cancer Society and the National Cancer Institute.

CHICAGO – Denosumab, a drug newly approved for prevention of skeletal-related adverse events in cancer patients with bone metastases from solid tumors, is not cost effective when compared with zoledronic acid in patients with breast or prostate cancers, according to a pair of pharmacoeconomic analyses.

A review of data from a key phase III trial in 2,046 patients with metastatic breast cancer found the cost per quality-adjusted life-year (QALY) gained with denosumab (Xgeva) was $643,726 when compared with zoledronic acid (Zometa), John A. Carter and his coinvestigators reported in a poster presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

This ratio is far higher than the $50,000 to $100,000 that is considered to be good value for a medical intervention, they said.

A related study in castration-resistant prostate cancer metastatic to the bone found even more substantial cost differentials. The resultant cost per QALY for denosumab would be approximately $1.25 million in this setting, reported Sonya H. Snedecor, Ph.D., and her coauthors in the second poster.

In both studies, investigators attributed the high cost per QALY to the higher drug acquisition cost of denosumab combined with limited added prevention of skeletal-related events (SREs) and a lack of overall survival or disease progression benefits for denosumab vs. zoledronic acid.

"What we found [in the prostate cancer study] is that there were very little gains in quality-adjusted life-years with the use of denosumab – very, very minuscule, about five per thousandths of a year," senior author Marc Botteman said in an interview.

"So you spend $5,000 to get that five per thousandths of a year, and that leads to a cost-effectiveness ratio of $1.25 million, which is way, way, way higher than what people typically consider to be acceptable in general, or in oncology," said Mr. Botteman, cofounder and managing partner of Pharmerit North America, a health economics and outcomes research firm that conducted the analyses. Both studies were sponsored by Novartis, maker of zoledronic acid.

For the two studies, Pharmerit developed a Markov model based on trial data to estimate survival, QALYs, number and costs of skeletal-related events, and drug and administration costs. QALYs were estimated by assigning utilities to four health states: prior to skeletal-related event; the event; post-event; and death.

"Quality-adjusted life-years are a metric used by health economists to estimate the value of treatment in terms of clinical benefits. The index combines survival and quality of life during that survival," Mr. Botteman said.

Denosumab maker Amgen responded to a request for a response with an e-mailed statement that challenged the models’ use of event rates based on clinical trials rather than event rates observed in real-world clinical practice. Amgen also contended that the models underestimate the value of denosumab "by attributing lower costs to SREs than those seen in the real world," and it criticized the limited time frames used in the models.

"Economic models should extend far enough into the future to capture the major health and economic outcomes. By truncating the modeling time frame the value of preventing/delaying SREs will also be reduced," it said.

The statement also touted denosumab’s superiority in preventing SREs in patients with advanced solid tumors, and contended that this "could result in direct cost offsets due to reduced incidence of SREs and related medical costs."

"Amgen stands by the value of Xgeva for patients, health care providers, and payers," the statement concluded, citing denosumab’s safety profile, subcutaneous administration, and other attributes not covered by Pharmerit’s model.

The breast cancer poster used data from a phase III trial that contributed to the Food and Drug Administration’s decision in November 2010 to approve denusumab for the prevention of SREs in patients with bone metastases from solid tumors. The trial found denosumab to be superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer that had spread to the bone. Both drugs showed similar results in overall survival, disease progression, and serious adverse events (J. Clin. Onc. 2010;28:5132-39).

The poster reported the cost of a denusumab injection to be nearly twice that of zoledronic acid, at $1,650 vs. $887. Compared with the older drug, denosumab was found to result in fewer SREs and resultant costs, and slightly more QALYs. It was associated with higher drug-related costs, however.

As a result, total discounted costs were higher for denosumab by an addition of $6,884 per patient over the period of analysis. The cost per QALY gained was $644,000 when excluding SREs and $613,000 per QALY when including SREs, the authors wrote.

Discussing the poster at the ASCO meeting, Dr. Thomas J. Smith of the Massey Cancer Center at Virginia Commonwealth University, Richmond, said it "raises some significant concern about money-driven value in metastatic breast cancer treatment."

Dr. Smith said that the study raises questions about physicians’ ability to negotiate prices, and how to use these data in making decisions. "I can tell you that at most hospitals, most P&T [pharmacy and therapeutics] committees have wrestled exactly with this, ... and where does this fit in pathway-driven managed care, where you get a fixed amount to take care of these patients?" he said.

That the analysis was funded by the maker of zoledronic acid also was a concern. "So I would wait to draw conclusions until this has been through peer review," Dr. Smith said.

The prostate cancer study found that denosumab marginally improved quality of life (+0.0043 QALYs) relative to zoledronic acid, and reduced costs of SREs by $1,924 based on a calculation that these would cost $7,604 with denosumab vs. $9,528 with zoledronic acid over 27 months of treatment. To achieve those benefits, the patient would have to invest more than $7,313 in additional drug costs with denosumab, and thus incur a net cost of $5,390 over 27 months, according to the study.

Novartis, the maker of zoledronic acid, sponsored both studies. Mr. Carter and Dr. Snedecor disclosed consultant or advisory roles with Novartis. One of their coauthors was a Novartis employee with stock ownership. Mr. Botteman disclosed consultant or advisory roles with Pharmerit. Dr. Smith disclosed research funding from the American Cancer Society and the National Cancer Institute.

CHICAGO – Denosumab, a drug newly approved for prevention of skeletal-related adverse events in cancer patients with bone metastases from solid tumors, is not cost effective when compared with zoledronic acid in patients with breast or prostate cancers, according to a pair of pharmacoeconomic analyses.

A review of data from a key phase III trial in 2,046 patients with metastatic breast cancer found the cost per quality-adjusted life-year (QALY) gained with denosumab (Xgeva) was $643,726 when compared with zoledronic acid (Zometa), John A. Carter and his coinvestigators reported in a poster presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

This ratio is far higher than the $50,000 to $100,000 that is considered to be good value for a medical intervention, they said.

A related study in castration-resistant prostate cancer metastatic to the bone found even more substantial cost differentials. The resultant cost per QALY for denosumab would be approximately $1.25 million in this setting, reported Sonya H. Snedecor, Ph.D., and her coauthors in the second poster.

In both studies, investigators attributed the high cost per QALY to the higher drug acquisition cost of denosumab combined with limited added prevention of skeletal-related events (SREs) and a lack of overall survival or disease progression benefits for denosumab vs. zoledronic acid.

"What we found [in the prostate cancer study] is that there were very little gains in quality-adjusted life-years with the use of denosumab – very, very minuscule, about five per thousandths of a year," senior author Marc Botteman said in an interview.

"So you spend $5,000 to get that five per thousandths of a year, and that leads to a cost-effectiveness ratio of $1.25 million, which is way, way, way higher than what people typically consider to be acceptable in general, or in oncology," said Mr. Botteman, cofounder and managing partner of Pharmerit North America, a health economics and outcomes research firm that conducted the analyses. Both studies were sponsored by Novartis, maker of zoledronic acid.

For the two studies, Pharmerit developed a Markov model based on trial data to estimate survival, QALYs, number and costs of skeletal-related events, and drug and administration costs. QALYs were estimated by assigning utilities to four health states: prior to skeletal-related event; the event; post-event; and death.

"Quality-adjusted life-years are a metric used by health economists to estimate the value of treatment in terms of clinical benefits. The index combines survival and quality of life during that survival," Mr. Botteman said.

Denosumab maker Amgen responded to a request for a response with an e-mailed statement that challenged the models’ use of event rates based on clinical trials rather than event rates observed in real-world clinical practice. Amgen also contended that the models underestimate the value of denosumab "by attributing lower costs to SREs than those seen in the real world," and it criticized the limited time frames used in the models.

"Economic models should extend far enough into the future to capture the major health and economic outcomes. By truncating the modeling time frame the value of preventing/delaying SREs will also be reduced," it said.

The statement also touted denosumab’s superiority in preventing SREs in patients with advanced solid tumors, and contended that this "could result in direct cost offsets due to reduced incidence of SREs and related medical costs."

"Amgen stands by the value of Xgeva for patients, health care providers, and payers," the statement concluded, citing denosumab’s safety profile, subcutaneous administration, and other attributes not covered by Pharmerit’s model.

The breast cancer poster used data from a phase III trial that contributed to the Food and Drug Administration’s decision in November 2010 to approve denusumab for the prevention of SREs in patients with bone metastases from solid tumors. The trial found denosumab to be superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer that had spread to the bone. Both drugs showed similar results in overall survival, disease progression, and serious adverse events (J. Clin. Onc. 2010;28:5132-39).

The poster reported the cost of a denusumab injection to be nearly twice that of zoledronic acid, at $1,650 vs. $887. Compared with the older drug, denosumab was found to result in fewer SREs and resultant costs, and slightly more QALYs. It was associated with higher drug-related costs, however.

As a result, total discounted costs were higher for denosumab by an addition of $6,884 per patient over the period of analysis. The cost per QALY gained was $644,000 when excluding SREs and $613,000 per QALY when including SREs, the authors wrote.

Discussing the poster at the ASCO meeting, Dr. Thomas J. Smith of the Massey Cancer Center at Virginia Commonwealth University, Richmond, said it "raises some significant concern about money-driven value in metastatic breast cancer treatment."

Dr. Smith said that the study raises questions about physicians’ ability to negotiate prices, and how to use these data in making decisions. "I can tell you that at most hospitals, most P&T [pharmacy and therapeutics] committees have wrestled exactly with this, ... and where does this fit in pathway-driven managed care, where you get a fixed amount to take care of these patients?" he said.

That the analysis was funded by the maker of zoledronic acid also was a concern. "So I would wait to draw conclusions until this has been through peer review," Dr. Smith said.

The prostate cancer study found that denosumab marginally improved quality of life (+0.0043 QALYs) relative to zoledronic acid, and reduced costs of SREs by $1,924 based on a calculation that these would cost $7,604 with denosumab vs. $9,528 with zoledronic acid over 27 months of treatment. To achieve those benefits, the patient would have to invest more than $7,313 in additional drug costs with denosumab, and thus incur a net cost of $5,390 over 27 months, according to the study.

Novartis, the maker of zoledronic acid, sponsored both studies. Mr. Carter and Dr. Snedecor disclosed consultant or advisory roles with Novartis. One of their coauthors was a Novartis employee with stock ownership. Mr. Botteman disclosed consultant or advisory roles with Pharmerit. Dr. Smith disclosed research funding from the American Cancer Society and the National Cancer Institute.

CHICAGO – Denosumab, a drug newly approved for prevention of skeletal-related adverse events in cancer patients with bone metastases from solid tumors, is not cost effective when compared with zoledronic acid in patients with breast or prostate cancers, according to a pair of pharmacoeconomic analyses.

A review of data from a key phase III trial in 2,046 patients with metastatic breast cancer found the cost per quality-adjusted life-year (QALY) gained with denosumab (Xgeva) was $643,726 when compared with zoledronic acid (Zometa), John A. Carter and his coinvestigators reported in a poster presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

This ratio is far higher than the $50,000 to $100,000 that is considered to be good value for a medical intervention, they said.

A related study in castration-resistant prostate cancer metastatic to the bone found even more substantial cost differentials. The resultant cost per QALY for denosumab would be approximately $1.25 million in this setting, reported Sonya H. Snedecor, Ph.D., and her coauthors in the second poster.

In both studies, investigators attributed the high cost per QALY to the higher drug acquisition cost of denosumab combined with limited added prevention of skeletal-related events (SREs) and a lack of overall survival or disease progression benefits for denosumab vs. zoledronic acid.

"What we found [in the prostate cancer study] is that there were very little gains in quality-adjusted life-years with the use of denosumab – very, very minuscule, about five per thousandths of a year," senior author Marc Botteman said in an interview.

"So you spend $5,000 to get that five per thousandths of a year, and that leads to a cost-effectiveness ratio of $1.25 million, which is way, way, way higher than what people typically consider to be acceptable in general, or in oncology," said Mr. Botteman, cofounder and managing partner of Pharmerit North America, a health economics and outcomes research firm that conducted the analyses. Both studies were sponsored by Novartis, maker of zoledronic acid.

For the two studies, Pharmerit developed a Markov model based on trial data to estimate survival, QALYs, number and costs of skeletal-related events, and drug and administration costs. QALYs were estimated by assigning utilities to four health states: prior to skeletal-related event; the event; post-event; and death.

"Quality-adjusted life-years are a metric used by health economists to estimate the value of treatment in terms of clinical benefits. The index combines survival and quality of life during that survival," Mr. Botteman said.

Denosumab maker Amgen responded to a request for a response with an e-mailed statement that challenged the models’ use of event rates based on clinical trials rather than event rates observed in real-world clinical practice. Amgen also contended that the models underestimate the value of denosumab "by attributing lower costs to SREs than those seen in the real world," and it criticized the limited time frames used in the models.

"Economic models should extend far enough into the future to capture the major health and economic outcomes. By truncating the modeling time frame the value of preventing/delaying SREs will also be reduced," it said.

The statement also touted denosumab’s superiority in preventing SREs in patients with advanced solid tumors, and contended that this "could result in direct cost offsets due to reduced incidence of SREs and related medical costs."

"Amgen stands by the value of Xgeva for patients, health care providers, and payers," the statement concluded, citing denosumab’s safety profile, subcutaneous administration, and other attributes not covered by Pharmerit’s model.

The breast cancer poster used data from a phase III trial that contributed to the Food and Drug Administration’s decision in November 2010 to approve denusumab for the prevention of SREs in patients with bone metastases from solid tumors. The trial found denosumab to be superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer that had spread to the bone. Both drugs showed similar results in overall survival, disease progression, and serious adverse events (J. Clin. Onc. 2010;28:5132-39).

The poster reported the cost of a denusumab injection to be nearly twice that of zoledronic acid, at $1,650 vs. $887. Compared with the older drug, denosumab was found to result in fewer SREs and resultant costs, and slightly more QALYs. It was associated with higher drug-related costs, however.

As a result, total discounted costs were higher for denosumab by an addition of $6,884 per patient over the period of analysis. The cost per QALY gained was $644,000 when excluding SREs and $613,000 per QALY when including SREs, the authors wrote.

Discussing the poster at the ASCO meeting, Dr. Thomas J. Smith of the Massey Cancer Center at Virginia Commonwealth University, Richmond, said it "raises some significant concern about money-driven value in metastatic breast cancer treatment."

Dr. Smith said that the study raises questions about physicians’ ability to negotiate prices, and how to use these data in making decisions. "I can tell you that at most hospitals, most P&T [pharmacy and therapeutics] committees have wrestled exactly with this, ... and where does this fit in pathway-driven managed care, where you get a fixed amount to take care of these patients?" he said.

That the analysis was funded by the maker of zoledronic acid also was a concern. "So I would wait to draw conclusions until this has been through peer review," Dr. Smith said.

The prostate cancer study found that denosumab marginally improved quality of life (+0.0043 QALYs) relative to zoledronic acid, and reduced costs of SREs by $1,924 based on a calculation that these would cost $7,604 with denosumab vs. $9,528 with zoledronic acid over 27 months of treatment. To achieve those benefits, the patient would have to invest more than $7,313 in additional drug costs with denosumab, and thus incur a net cost of $5,390 over 27 months, according to the study.

Novartis, the maker of zoledronic acid, sponsored both studies. Mr. Carter and Dr. Snedecor disclosed consultant or advisory roles with Novartis. One of their coauthors was a Novartis employee with stock ownership. Mr. Botteman disclosed consultant or advisory roles with Pharmerit. Dr. Smith disclosed research funding from the American Cancer Society and the National Cancer Institute.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – The investigational drug axitinib prolonged median progression-free survival by 2 months, compared with sorafenib, in a randomized, phase III trial that was conducted in patients with metastatic renal cell carcinoma resistant to initial therapy.

The international 723-patient AXIS (Axitinib [AG 013736] for the Treatment of Metastatic Renal Cell Cancer) trial was the first to compare targeted second-line therapies in this or any setting, according to lead author Dr. Brian I. Rini of the Cleveland Clinic Foundation, who presented the results at the annual meeting of the American Society of Clinical Oncology.

Sorafenib (Nexavar), a multitargeted kinase inhibitor, is approved for the treatment of advanced kidney cancer. Axitinib, a selective second-generation inhibitor of VEGF (vascular endothelial growth factor) receptor–1, -2 and -3, has demonstrated antitumor activity in phase II trials in kidney cancer.

Dr. Rini said that the new trial data support a hypothesis that more potent biochemical targeting of the VEGF receptor was associated with superior clinical activity in renal cell carcinoma. "Axitinib should now be considered as the reference standard in second-line treatment of advanced renal cell carcinoma," he said.

To be eligible for this trial, patients had to have metastatic renal cell carcinoma with clear cell histology and disease measurable by RECIST (Response Evaluation Criteria in Solid Tumors), including progressive disease after one prior treatment with a cytokine-based regimen or a single treatment with sunitinib (Sutent); bevacizumab (Avastin) plus interferon-alpha; or temsirolimus (Torisel).

Investigators randomized 361 patients to axitinib (5 mg twice a day, with the option for titration up to 10 mg as tolerated) and 362 to sorafenib (400 mg twice a day). The population had a median age of 61 years. White men accounted for about three-quarters of the cohort; more than 20% were of Asian descent. Eastern Cooperative Oncology Group performance status was equally distributed between 0 and 1, and was balanced between the arms.

More than half of the patients (389) had received prior sunitinib, a multitargeted tyrosine kinase inhibitor (TKI). Other previous therapies were cytokines (in 251 patients), the VEGF inhibitor bevacizumab (59), and the mTOR (mammalian target of rapamycin) inhibitor temsirolimus (24).

Patients who were treated with axitinib had a median progression-free survival of 6.7 months vs. 4.7 months with sorafenib (stratified hazard ratio, 0.665; P less than .0001). The difference as assessed by an independent review committee was most pronounced in patients with prior cytokine therapy: 12.1 months with axitinib vs. 6.5 months with sorafenib (HR, 0.464; P less than .0001).

The difference in patients with prior sunitinib was smaller but also statistically significant (4.8 months with axitinib vs. 3.4 months with sorafenib; HR, 0.74; P = .011). The number of patients with prior temsirolimus or bevacizumab therapy was too small for meaningful comparison, Dr. Rini said.

Overall survival data were not yet mature.

The analysis of best response by RECIST showed a higher partial response rate of 19.4% with axitinib vs. 9.4 % with sunitinib. Discontinuations because of treatment-related adverse events were more common in the sorafenib arm (8.2%, compared with 3.9% of patients on axitinib).

Dr. Rini characterized the new agent’s safety profile as generally similar to that of sorafenib, with exceptions: The axitinib arm had more hypertension and hyperthyroidism, and less hand-foot syndrome, rash, and alopecia. Click here to view a video interview with Dr. Rini.

A related abstract presented by Dr. David Cella of Northwestern University, Chicago, addressed whether prolongation of progression-free survival corresponded with delay of symptoms. It found that axitinib treatment resulted in overall FKSI (Functional Assessment of Cancer Therapy–Kidney Cancer Symptom Index) scores similar to those recorded for sorafenib.

Axitinib demonstrated a 16%-17% risk reduction in time to deterioration for the composite end point of progression, death, or deterioration in health-related quality of life, he said. These results supported the primary efficacy analysis and indicated the value of progression-free survival in metastatic renal cell carcinoma, Dr. Cella said.

"What we learned from looking at the symptom data included is [that] the benefit of progression-free survival certainly does not wash away because of treatment toxicity," he said.

Discussant Dr. Bruce G. Redman of the University of Michigan, Ann Arbor, agreed that axitinib was well tolerated for the treatment of metastatic renal cell carcinoma, and was a valid treatment option after prior therapy with interleukin-2, as well as a "reasonable" option after prior TKI therapy.

Dr. Redman questioned Dr. Rini’s conclusion that axitinib should be considered as a reference standard in second-line treatment of advanced renal cell carcinoma, however. "Other than the obvious fact that axitinib is still considered an investigational agent," Dr. Redman noted that there was "a marked improvement" in the patients treated with prior cytokines. In this study and in previous trials with patients who had prior TKIs, progression-free survival with TKI or mTOR therapy was in the 4- to 5-month range.

Key questions, he suggested, are, What is the role of a second TKI after progression with a first TKI, and does it matter whether patients benefited from the first TKI when choosing second-line therapy? "But more importantly, [with] my apologies to industry, Do we need more TKIs or mTOR inhibitors, or do we want a new target in this disease?" asked Dr. Redman.

Pfizer sponsored the AXIS trial. Dr. Rini disclosed an advisory role with and research funding from Pfizer. Dr. Cella disclosed advisory roles with AVEO, Bayer, and Pfizer, and research funding from AVEO, Bayer, Novartis, and Pfizer. Dr. Redman disclosed stock ownership in Novartis.

CHICAGO – A randomized, multicenter open-label trial found that cyclosporine was not more effective than infliximab in patients with acute, severe ulcerative colitis refractory to intravenous steroids, according to Dr. David Laharie.

Acute severe ulcerative colitis (UC) occurs in about 25% of patients with UC, and while intravenous corticosteroids are the primary therapy, 40% of patients are refractory to them. After steroid failure, only two medical options are available to avoid colectomy: cyclosporine and infliximab.

"However, there has been no randomized clinical trial comparing the two," said Dr. Laharie of Centre Hospitalier Universitaire in Bordeaux, France. He presented the findings of a multicenter, randomized open-label study comparing cyclosporine with infliximab in severe acute UC refractory to intravenous steroids. This study found cyclosporine to be no more effective than infliximab in this population, he said at the annual Digestive Disease Week.

Patients with steroid-refractory acute severe UC were randomized to cyclosporine (55 patients) or infliximab (56 patients). The researchers sought to determine whether treatment failure was less frequent with cyclosporine than with infliximab.

Adults were randomized if they were having a severe acute flare of UC (Lichtiger score greater than 10) and were refractory to intravenous steroid therapy (greater than or equal to 0.8 mg/kg per day of methylprednisone or equivalent) for at least 5 days. They had to be naive to the two treatment drugs and could not be under treatment with azathioprine/6-mercaptopurine unless therapy had been initiated fewer than 4 weeks before randomization.

The two groups were treated for up to 98 days, and the trial’s primary end point was treatment failure, defined as an absence of early clinical response, relapse after day 7, colectomy, absence of remission off steroids at the trial’s end, a severe adverse event, or death. Secondary end points included the Lichtiger score from day 0 to day 7, the percentage of patients showing clinical response at day 7, endoscopic response and colectomy at day 98, and the number of severe adverse events.

Approximately half the patients in both groups were female, with a median age of approximately 37 years, and had UC for at least 1 year. More than 90% of patients in both groups were naive to azathioprine. Lichtiger scores in both groups were 11 and over, and Mayo scores ranged from less than or equal to 0 to 12.

For the primary end point of treatment failure, 60% failed in the cyclosporine arm versus 54% in the infliximab arm, a nonsignificant difference.

The response rate at day 7 was 85.4% in the cyclosporine arm versus 85.7% in the infliximab arm, also not a significant difference. Response was defined as a Lichtiger score less than 10, and a decrease of at least 3 points compared with baseline.

The Lichtiger score from day 0 to day 6 showed that the median time to clinical response was 4 days (interquartile range [IQR], 3-6) with infliximab, versus 5 days (IQR, 4-7) for cyclosporine, a significant difference (P = .046).

At day 98, signs of mucosal healing were found in 52% of patients in the cyclosporine group and 53% of patients in the infliximab group. Healing was defined as having a Mayo endoscopic subscore of 0-1.

The colectomy rates were 18% in the cyclosporine arm and 21% in the infliximab arm. Severe adverse events affected 15% (8 patients) in the cyclosporine group and 25% (14 patients) in the infliximab group. Three patients developed cytomegalovirus colitis and two developed septicemia.

"In acute severe ulcerative colitis refractory to intravenous steroids, cyclosporine was not more effective than infliximab," said Dr. Laharie. "The short-term response was achieved with both drugs in more than 80% of patients within 1 week. Three-month colectomy rates were similar (18% with cyclosporine versus 21% with infliximab). And in this severe population, both drugs were well tolerated," he said.

Dr. Laharie disclosed financial relationships with Schering-Plough and Abbott Laboratories (royalty, speaking, and teaching), and with Norgine (consulting fee and board membership). The study received support from the Association François Aupetit, the Société Nationale Française de Gastro-Entérologie, and the International Organization for the Study of Inflammatory Bowel Disease, and was sponsored by Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

CHICAGO – A randomized, multicenter open-label trial found that cyclosporine was not more effective than infliximab in patients with acute, severe ulcerative colitis refractory to intravenous steroids, according to Dr. David Laharie.

Acute severe ulcerative colitis (UC) occurs in about 25% of patients with UC, and while intravenous corticosteroids are the primary therapy, 40% of patients are refractory to them. After steroid failure, only two medical options are available to avoid colectomy: cyclosporine and infliximab.

"However, there has been no randomized clinical trial comparing the two," said Dr. Laharie of Centre Hospitalier Universitaire in Bordeaux, France. He presented the findings of a multicenter, randomized open-label study comparing cyclosporine with infliximab in severe acute UC refractory to intravenous steroids. This study found cyclosporine to be no more effective than infliximab in this population, he said at the annual Digestive Disease Week.

Patients with steroid-refractory acute severe UC were randomized to cyclosporine (55 patients) or infliximab (56 patients). The researchers sought to determine whether treatment failure was less frequent with cyclosporine than with infliximab.

Adults were randomized if they were having a severe acute flare of UC (Lichtiger score greater than 10) and were refractory to intravenous steroid therapy (greater than or equal to 0.8 mg/kg per day of methylprednisone or equivalent) for at least 5 days. They had to be naive to the two treatment drugs and could not be under treatment with azathioprine/6-mercaptopurine unless therapy had been initiated fewer than 4 weeks before randomization.

The two groups were treated for up to 98 days, and the trial’s primary end point was treatment failure, defined as an absence of early clinical response, relapse after day 7, colectomy, absence of remission off steroids at the trial’s end, a severe adverse event, or death. Secondary end points included the Lichtiger score from day 0 to day 7, the percentage of patients showing clinical response at day 7, endoscopic response and colectomy at day 98, and the number of severe adverse events.

Approximately half the patients in both groups were female, with a median age of approximately 37 years, and had UC for at least 1 year. More than 90% of patients in both groups were naive to azathioprine. Lichtiger scores in both groups were 11 and over, and Mayo scores ranged from less than or equal to 0 to 12.

For the primary end point of treatment failure, 60% failed in the cyclosporine arm versus 54% in the infliximab arm, a nonsignificant difference.

The response rate at day 7 was 85.4% in the cyclosporine arm versus 85.7% in the infliximab arm, also not a significant difference. Response was defined as a Lichtiger score less than 10, and a decrease of at least 3 points compared with baseline.

The Lichtiger score from day 0 to day 6 showed that the median time to clinical response was 4 days (interquartile range [IQR], 3-6) with infliximab, versus 5 days (IQR, 4-7) for cyclosporine, a significant difference (P = .046).

At day 98, signs of mucosal healing were found in 52% of patients in the cyclosporine group and 53% of patients in the infliximab group. Healing was defined as having a Mayo endoscopic subscore of 0-1.

The colectomy rates were 18% in the cyclosporine arm and 21% in the infliximab arm. Severe adverse events affected 15% (8 patients) in the cyclosporine group and 25% (14 patients) in the infliximab group. Three patients developed cytomegalovirus colitis and two developed septicemia.

"In acute severe ulcerative colitis refractory to intravenous steroids, cyclosporine was not more effective than infliximab," said Dr. Laharie. "The short-term response was achieved with both drugs in more than 80% of patients within 1 week. Three-month colectomy rates were similar (18% with cyclosporine versus 21% with infliximab). And in this severe population, both drugs were well tolerated," he said.

Dr. Laharie disclosed financial relationships with Schering-Plough and Abbott Laboratories (royalty, speaking, and teaching), and with Norgine (consulting fee and board membership). The study received support from the Association François Aupetit, the Société Nationale Française de Gastro-Entérologie, and the International Organization for the Study of Inflammatory Bowel Disease, and was sponsored by Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

CHICAGO – A randomized, multicenter open-label trial found that cyclosporine was not more effective than infliximab in patients with acute, severe ulcerative colitis refractory to intravenous steroids, according to Dr. David Laharie.

Acute severe ulcerative colitis (UC) occurs in about 25% of patients with UC, and while intravenous corticosteroids are the primary therapy, 40% of patients are refractory to them. After steroid failure, only two medical options are available to avoid colectomy: cyclosporine and infliximab.

"However, there has been no randomized clinical trial comparing the two," said Dr. Laharie of Centre Hospitalier Universitaire in Bordeaux, France. He presented the findings of a multicenter, randomized open-label study comparing cyclosporine with infliximab in severe acute UC refractory to intravenous steroids. This study found cyclosporine to be no more effective than infliximab in this population, he said at the annual Digestive Disease Week.

Patients with steroid-refractory acute severe UC were randomized to cyclosporine (55 patients) or infliximab (56 patients). The researchers sought to determine whether treatment failure was less frequent with cyclosporine than with infliximab.

Adults were randomized if they were having a severe acute flare of UC (Lichtiger score greater than 10) and were refractory to intravenous steroid therapy (greater than or equal to 0.8 mg/kg per day of methylprednisone or equivalent) for at least 5 days. They had to be naive to the two treatment drugs and could not be under treatment with azathioprine/6-mercaptopurine unless therapy had been initiated fewer than 4 weeks before randomization.

The two groups were treated for up to 98 days, and the trial’s primary end point was treatment failure, defined as an absence of early clinical response, relapse after day 7, colectomy, absence of remission off steroids at the trial’s end, a severe adverse event, or death. Secondary end points included the Lichtiger score from day 0 to day 7, the percentage of patients showing clinical response at day 7, endoscopic response and colectomy at day 98, and the number of severe adverse events.

Approximately half the patients in both groups were female, with a median age of approximately 37 years, and had UC for at least 1 year. More than 90% of patients in both groups were naive to azathioprine. Lichtiger scores in both groups were 11 and over, and Mayo scores ranged from less than or equal to 0 to 12.

For the primary end point of treatment failure, 60% failed in the cyclosporine arm versus 54% in the infliximab arm, a nonsignificant difference.

The response rate at day 7 was 85.4% in the cyclosporine arm versus 85.7% in the infliximab arm, also not a significant difference. Response was defined as a Lichtiger score less than 10, and a decrease of at least 3 points compared with baseline.

The Lichtiger score from day 0 to day 6 showed that the median time to clinical response was 4 days (interquartile range [IQR], 3-6) with infliximab, versus 5 days (IQR, 4-7) for cyclosporine, a significant difference (P = .046).

At day 98, signs of mucosal healing were found in 52% of patients in the cyclosporine group and 53% of patients in the infliximab group. Healing was defined as having a Mayo endoscopic subscore of 0-1.

The colectomy rates were 18% in the cyclosporine arm and 21% in the infliximab arm. Severe adverse events affected 15% (8 patients) in the cyclosporine group and 25% (14 patients) in the infliximab group. Three patients developed cytomegalovirus colitis and two developed septicemia.

"In acute severe ulcerative colitis refractory to intravenous steroids, cyclosporine was not more effective than infliximab," said Dr. Laharie. "The short-term response was achieved with both drugs in more than 80% of patients within 1 week. Three-month colectomy rates were similar (18% with cyclosporine versus 21% with infliximab). And in this severe population, both drugs were well tolerated," he said.

Dr. Laharie disclosed financial relationships with Schering-Plough and Abbott Laboratories (royalty, speaking, and teaching), and with Norgine (consulting fee and board membership). The study received support from the Association François Aupetit, the Société Nationale Française de Gastro-Entérologie, and the International Organization for the Study of Inflammatory Bowel Disease, and was sponsored by Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

CHICAGO – A randomized, multicenter open-label trial found that cyclosporine was not more effective than infliximab in patients with acute, severe ulcerative colitis refractory to intravenous steroids, according to Dr. David Laharie.

Acute severe ulcerative colitis (UC) occurs in about 25% of patients with UC, and while intravenous corticosteroids are the primary therapy, 40% of patients are refractory to them. After steroid failure, only two medical options are available to avoid colectomy: cyclosporine and infliximab.

"However, there has been no randomized clinical trial comparing the two," said Dr. Laharie of Centre Hospitalier Universitaire in Bordeaux, France. He presented the findings of a multicenter, randomized open-label study comparing cyclosporine with infliximab in severe acute UC refractory to intravenous steroids. This study found cyclosporine to be no more effective than infliximab in this population, he said at the annual Digestive Disease Week.

Patients with steroid-refractory acute severe UC were randomized to cyclosporine (55 patients) or infliximab (56 patients). The researchers sought to determine whether treatment failure was less frequent with cyclosporine than with infliximab.

Adults were randomized if they were having a severe acute flare of UC (Lichtiger score greater than 10) and were refractory to intravenous steroid therapy (greater than or equal to 0.8 mg/kg per day of methylprednisone or equivalent) for at least 5 days. They had to be naive to the two treatment drugs and could not be under treatment with azathioprine/6-mercaptopurine unless therapy had been initiated fewer than 4 weeks before randomization.

The two groups were treated for up to 98 days, and the trial’s primary end point was treatment failure, defined as an absence of early clinical response, relapse after day 7, colectomy, absence of remission off steroids at the trial’s end, a severe adverse event, or death. Secondary end points included the Lichtiger score from day 0 to day 7, the percentage of patients showing clinical response at day 7, endoscopic response and colectomy at day 98, and the number of severe adverse events.

Approximately half the patients in both groups were female, with a median age of approximately 37 years, and had UC for at least 1 year. More than 90% of patients in both groups were naive to azathioprine. Lichtiger scores in both groups were 11 and over, and Mayo scores ranged from less than or equal to 0 to 12.

For the primary end point of treatment failure, 60% failed in the cyclosporine arm versus 54% in the infliximab arm, a nonsignificant difference.

The response rate at day 7 was 85.4% in the cyclosporine arm versus 85.7% in the infliximab arm, also not a significant difference. Response was defined as a Lichtiger score less than 10, and a decrease of at least 3 points compared with baseline.

The Lichtiger score from day 0 to day 6 showed that the median time to clinical response was 4 days (interquartile range [IQR], 3-6) with infliximab, versus 5 days (IQR, 4-7) for cyclosporine, a significant difference (P = .046).

At day 98, signs of mucosal healing were found in 52% of patients in the cyclosporine group and 53% of patients in the infliximab group. Healing was defined as having a Mayo endoscopic subscore of 0-1.

The colectomy rates were 18% in the cyclosporine arm and 21% in the infliximab arm. Severe adverse events affected 15% (8 patients) in the cyclosporine group and 25% (14 patients) in the infliximab group. Three patients developed cytomegalovirus colitis and two developed septicemia.

"In acute severe ulcerative colitis refractory to intravenous steroids, cyclosporine was not more effective than infliximab," said Dr. Laharie. "The short-term response was achieved with both drugs in more than 80% of patients within 1 week. Three-month colectomy rates were similar (18% with cyclosporine versus 21% with infliximab). And in this severe population, both drugs were well tolerated," he said.

Dr. Laharie disclosed financial relationships with Schering-Plough and Abbott Laboratories (royalty, speaking, and teaching), and with Norgine (consulting fee and board membership). The study received support from the Association François Aupetit, the Société Nationale Française de Gastro-Entérologie, and the International Organization for the Study of Inflammatory Bowel Disease, and was sponsored by Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

CHICAGO – A randomized, multicenter open-label trial found that cyclosporine was not more effective than infliximab in patients with acute, severe ulcerative colitis refractory to intravenous steroids, according to Dr. David Laharie.

Acute severe ulcerative colitis (UC) occurs in about 25% of patients with UC, and while intravenous corticosteroids are the primary therapy, 40% of patients are refractory to them. After steroid failure, only two medical options are available to avoid colectomy: cyclosporine and infliximab.

"However, there has been no randomized clinical trial comparing the two," said Dr. Laharie of Centre Hospitalier Universitaire in Bordeaux, France. He presented the findings of a multicenter, randomized open-label study comparing cyclosporine with infliximab in severe acute UC refractory to intravenous steroids. This study found cyclosporine to be no more effective than infliximab in this population, he said at the annual Digestive Disease Week.

Patients with steroid-refractory acute severe UC were randomized to cyclosporine (55 patients) or infliximab (56 patients). The researchers sought to determine whether treatment failure was less frequent with cyclosporine than with infliximab.

Adults were randomized if they were having a severe acute flare of UC (Lichtiger score greater than 10) and were refractory to intravenous steroid therapy (greater than or equal to 0.8 mg/kg per day of methylprednisone or equivalent) for at least 5 days. They had to be naive to the two treatment drugs and could not be under treatment with azathioprine/6-mercaptopurine unless therapy had been initiated fewer than 4 weeks before randomization.

The two groups were treated for up to 98 days, and the trial’s primary end point was treatment failure, defined as an absence of early clinical response, relapse after day 7, colectomy, absence of remission off steroids at the trial’s end, a severe adverse event, or death. Secondary end points included the Lichtiger score from day 0 to day 7, the percentage of patients showing clinical response at day 7, endoscopic response and colectomy at day 98, and the number of severe adverse events.

Approximately half the patients in both groups were female, with a median age of approximately 37 years, and had UC for at least 1 year. More than 90% of patients in both groups were naive to azathioprine. Lichtiger scores in both groups were 11 and over, and Mayo scores ranged from less than or equal to 0 to 12.

For the primary end point of treatment failure, 60% failed in the cyclosporine arm versus 54% in the infliximab arm, a nonsignificant difference.

The response rate at day 7 was 85.4% in the cyclosporine arm versus 85.7% in the infliximab arm, also not a significant difference. Response was defined as a Lichtiger score less than 10, and a decrease of at least 3 points compared with baseline.

The Lichtiger score from day 0 to day 6 showed that the median time to clinical response was 4 days (interquartile range [IQR], 3-6) with infliximab, versus 5 days (IQR, 4-7) for cyclosporine, a significant difference (P = .046).

At day 98, signs of mucosal healing were found in 52% of patients in the cyclosporine group and 53% of patients in the infliximab group. Healing was defined as having a Mayo endoscopic subscore of 0-1.

The colectomy rates were 18% in the cyclosporine arm and 21% in the infliximab arm. Severe adverse events affected 15% (8 patients) in the cyclosporine group and 25% (14 patients) in the infliximab group. Three patients developed cytomegalovirus colitis and two developed septicemia.

"In acute severe ulcerative colitis refractory to intravenous steroids, cyclosporine was not more effective than infliximab," said Dr. Laharie. "The short-term response was achieved with both drugs in more than 80% of patients within 1 week. Three-month colectomy rates were similar (18% with cyclosporine versus 21% with infliximab). And in this severe population, both drugs were well tolerated," he said.

Dr. Laharie disclosed financial relationships with Schering-Plough and Abbott Laboratories (royalty, speaking, and teaching), and with Norgine (consulting fee and board membership). The study received support from the Association François Aupetit, the Société Nationale Française de Gastro-Entérologie, and the International Organization for the Study of Inflammatory Bowel Disease, and was sponsored by Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

CHICAGO – A randomized, multicenter open-label trial found that cyclosporine was not more effective than infliximab in patients with acute, severe ulcerative colitis refractory to intravenous steroids, according to Dr. David Laharie.

Acute severe ulcerative colitis (UC) occurs in about 25% of patients with UC, and while intravenous corticosteroids are the primary therapy, 40% of patients are refractory to them. After steroid failure, only two medical options are available to avoid colectomy: cyclosporine and infliximab.

"However, there has been no randomized clinical trial comparing the two," said Dr. Laharie of Centre Hospitalier Universitaire in Bordeaux, France. He presented the findings of a multicenter, randomized open-label study comparing cyclosporine with infliximab in severe acute UC refractory to intravenous steroids. This study found cyclosporine to be no more effective than infliximab in this population, he said at the annual Digestive Disease Week.

Patients with steroid-refractory acute severe UC were randomized to cyclosporine (55 patients) or infliximab (56 patients). The researchers sought to determine whether treatment failure was less frequent with cyclosporine than with infliximab.

Adults were randomized if they were having a severe acute flare of UC (Lichtiger score greater than 10) and were refractory to intravenous steroid therapy (greater than or equal to 0.8 mg/kg per day of methylprednisone or equivalent) for at least 5 days. They had to be naive to the two treatment drugs and could not be under treatment with azathioprine/6-mercaptopurine unless therapy had been initiated fewer than 4 weeks before randomization.

The two groups were treated for up to 98 days, and the trial’s primary end point was treatment failure, defined as an absence of early clinical response, relapse after day 7, colectomy, absence of remission off steroids at the trial’s end, a severe adverse event, or death. Secondary end points included the Lichtiger score from day 0 to day 7, the percentage of patients showing clinical response at day 7, endoscopic response and colectomy at day 98, and the number of severe adverse events.

Approximately half the patients in both groups were female, with a median age of approximately 37 years, and had UC for at least 1 year. More than 90% of patients in both groups were naive to azathioprine. Lichtiger scores in both groups were 11 and over, and Mayo scores ranged from less than or equal to 0 to 12.

For the primary end point of treatment failure, 60% failed in the cyclosporine arm versus 54% in the infliximab arm, a nonsignificant difference.

The response rate at day 7 was 85.4% in the cyclosporine arm versus 85.7% in the infliximab arm, also not a significant difference. Response was defined as a Lichtiger score less than 10, and a decrease of at least 3 points compared with baseline.

The Lichtiger score from day 0 to day 6 showed that the median time to clinical response was 4 days (interquartile range [IQR], 3-6) with infliximab, versus 5 days (IQR, 4-7) for cyclosporine, a significant difference (P = .046).

At day 98, signs of mucosal healing were found in 52% of patients in the cyclosporine group and 53% of patients in the infliximab group. Healing was defined as having a Mayo endoscopic subscore of 0-1.

The colectomy rates were 18% in the cyclosporine arm and 21% in the infliximab arm. Severe adverse events affected 15% (8 patients) in the cyclosporine group and 25% (14 patients) in the infliximab group. Three patients developed cytomegalovirus colitis and two developed septicemia.

"In acute severe ulcerative colitis refractory to intravenous steroids, cyclosporine was not more effective than infliximab," said Dr. Laharie. "The short-term response was achieved with both drugs in more than 80% of patients within 1 week. Three-month colectomy rates were similar (18% with cyclosporine versus 21% with infliximab). And in this severe population, both drugs were well tolerated," he said.

Dr. Laharie disclosed financial relationships with Schering-Plough and Abbott Laboratories (royalty, speaking, and teaching), and with Norgine (consulting fee and board membership). The study received support from the Association François Aupetit, the Société Nationale Française de Gastro-Entérologie, and the International Organization for the Study of Inflammatory Bowel Disease, and was sponsored by Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

CHICAGO – A randomized, multicenter open-label trial found that cyclosporine was not more effective than infliximab in patients with acute, severe ulcerative colitis refractory to intravenous steroids, according to Dr. David Laharie.

Acute severe ulcerative colitis (UC) occurs in about 25% of patients with UC, and while intravenous corticosteroids are the primary therapy, 40% of patients are refractory to them. After steroid failure, only two medical options are available to avoid colectomy: cyclosporine and infliximab.

"However, there has been no randomized clinical trial comparing the two," said Dr. Laharie of Centre Hospitalier Universitaire in Bordeaux, France. He presented the findings of a multicenter, randomized open-label study comparing cyclosporine with infliximab in severe acute UC refractory to intravenous steroids. This study found cyclosporine to be no more effective than infliximab in this population, he said at the annual Digestive Disease Week.

Patients with steroid-refractory acute severe UC were randomized to cyclosporine (55 patients) or infliximab (56 patients). The researchers sought to determine whether treatment failure was less frequent with cyclosporine than with infliximab.

Adults were randomized if they were having a severe acute flare of UC (Lichtiger score greater than 10) and were refractory to intravenous steroid therapy (greater than or equal to 0.8 mg/kg per day of methylprednisone or equivalent) for at least 5 days. They had to be naive to the two treatment drugs and could not be under treatment with azathioprine/6-mercaptopurine unless therapy had been initiated fewer than 4 weeks before randomization.

The two groups were treated for up to 98 days, and the trial’s primary end point was treatment failure, defined as an absence of early clinical response, relapse after day 7, colectomy, absence of remission off steroids at the trial’s end, a severe adverse event, or death. Secondary end points included the Lichtiger score from day 0 to day 7, the percentage of patients showing clinical response at day 7, endoscopic response and colectomy at day 98, and the number of severe adverse events.

Approximately half the patients in both groups were female, with a median age of approximately 37 years, and had UC for at least 1 year. More than 90% of patients in both groups were naive to azathioprine. Lichtiger scores in both groups were 11 and over, and Mayo scores ranged from less than or equal to 0 to 12.

For the primary end point of treatment failure, 60% failed in the cyclosporine arm versus 54% in the infliximab arm, a nonsignificant difference.

The response rate at day 7 was 85.4% in the cyclosporine arm versus 85.7% in the infliximab arm, also not a significant difference. Response was defined as a Lichtiger score less than 10, and a decrease of at least 3 points compared with baseline.

The Lichtiger score from day 0 to day 6 showed that the median time to clinical response was 4 days (interquartile range [IQR], 3-6) with infliximab, versus 5 days (IQR, 4-7) for cyclosporine, a significant difference (P = .046).

At day 98, signs of mucosal healing were found in 52% of patients in the cyclosporine group and 53% of patients in the infliximab group. Healing was defined as having a Mayo endoscopic subscore of 0-1.

The colectomy rates were 18% in the cyclosporine arm and 21% in the infliximab arm. Severe adverse events affected 15% (8 patients) in the cyclosporine group and 25% (14 patients) in the infliximab group. Three patients developed cytomegalovirus colitis and two developed septicemia.

"In acute severe ulcerative colitis refractory to intravenous steroids, cyclosporine was not more effective than infliximab," said Dr. Laharie. "The short-term response was achieved with both drugs in more than 80% of patients within 1 week. Three-month colectomy rates were similar (18% with cyclosporine versus 21% with infliximab). And in this severe population, both drugs were well tolerated," he said.

Dr. Laharie disclosed financial relationships with Schering-Plough and Abbott Laboratories (royalty, speaking, and teaching), and with Norgine (consulting fee and board membership). The study received support from the Association François Aupetit, the Société Nationale Française de Gastro-Entérologie, and the International Organization for the Study of Inflammatory Bowel Disease, and was sponsored by Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

CHICAGO – A randomized, multicenter open-label trial found that cyclosporine was not more effective than infliximab in patients with acute, severe ulcerative colitis refractory to intravenous steroids, according to Dr. David Laharie.

Acute severe ulcerative colitis (UC) occurs in about 25% of patients with UC, and while intravenous corticosteroids are the primary therapy, 40% of patients are refractory to them. After steroid failure, only two medical options are available to avoid colectomy: cyclosporine and infliximab.

"However, there has been no randomized clinical trial comparing the two," said Dr. Laharie of Centre Hospitalier Universitaire in Bordeaux, France. He presented the findings of a multicenter, randomized open-label study comparing cyclosporine with infliximab in severe acute UC refractory to intravenous steroids. This study found cyclosporine to be no more effective than infliximab in this population, he said at the annual Digestive Disease Week.

Patients with steroid-refractory acute severe UC were randomized to cyclosporine (55 patients) or infliximab (56 patients). The researchers sought to determine whether treatment failure was less frequent with cyclosporine than with infliximab.

Adults were randomized if they were having a severe acute flare of UC (Lichtiger score greater than 10) and were refractory to intravenous steroid therapy (greater than or equal to 0.8 mg/kg per day of methylprednisone or equivalent) for at least 5 days. They had to be naive to the two treatment drugs and could not be under treatment with azathioprine/6-mercaptopurine unless therapy had been initiated fewer than 4 weeks before randomization.

The two groups were treated for up to 98 days, and the trial’s primary end point was treatment failure, defined as an absence of early clinical response, relapse after day 7, colectomy, absence of remission off steroids at the trial’s end, a severe adverse event, or death. Secondary end points included the Lichtiger score from day 0 to day 7, the percentage of patients showing clinical response at day 7, endoscopic response and colectomy at day 98, and the number of severe adverse events.

Approximately half the patients in both groups were female, with a median age of approximately 37 years, and had UC for at least 1 year. More than 90% of patients in both groups were naive to azathioprine. Lichtiger scores in both groups were 11 and over, and Mayo scores ranged from less than or equal to 0 to 12.

For the primary end point of treatment failure, 60% failed in the cyclosporine arm versus 54% in the infliximab arm, a nonsignificant difference.

The response rate at day 7 was 85.4% in the cyclosporine arm versus 85.7% in the infliximab arm, also not a significant difference. Response was defined as a Lichtiger score less than 10, and a decrease of at least 3 points compared with baseline.

The Lichtiger score from day 0 to day 6 showed that the median time to clinical response was 4 days (interquartile range [IQR], 3-6) with infliximab, versus 5 days (IQR, 4-7) for cyclosporine, a significant difference (P = .046).

At day 98, signs of mucosal healing were found in 52% of patients in the cyclosporine group and 53% of patients in the infliximab group. Healing was defined as having a Mayo endoscopic subscore of 0-1.

The colectomy rates were 18% in the cyclosporine arm and 21% in the infliximab arm. Severe adverse events affected 15% (8 patients) in the cyclosporine group and 25% (14 patients) in the infliximab group. Three patients developed cytomegalovirus colitis and two developed septicemia.

"In acute severe ulcerative colitis refractory to intravenous steroids, cyclosporine was not more effective than infliximab," said Dr. Laharie. "The short-term response was achieved with both drugs in more than 80% of patients within 1 week. Three-month colectomy rates were similar (18% with cyclosporine versus 21% with infliximab). And in this severe population, both drugs were well tolerated," he said.

Dr. Laharie disclosed financial relationships with Schering-Plough and Abbott Laboratories (royalty, speaking, and teaching), and with Norgine (consulting fee and board membership). The study received support from the Association François Aupetit, the Société Nationale Française de Gastro-Entérologie, and the International Organization for the Study of Inflammatory Bowel Disease, and was sponsored by Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

CHICAGO – A randomized, multicenter open-label trial found that cyclosporine was not more effective than infliximab in patients with acute, severe ulcerative colitis refractory to intravenous steroids, according to Dr. David Laharie.

Acute severe ulcerative colitis (UC) occurs in about 25% of patients with UC, and while intravenous corticosteroids are the primary therapy, 40% of patients are refractory to them. After steroid failure, only two medical options are available to avoid colectomy: cyclosporine and infliximab.

"However, there has been no randomized clinical trial comparing the two," said Dr. Laharie of Centre Hospitalier Universitaire in Bordeaux, France. He presented the findings of a multicenter, randomized open-label study comparing cyclosporine with infliximab in severe acute UC refractory to intravenous steroids. This study found cyclosporine to be no more effective than infliximab in this population, he said at the annual Digestive Disease Week.

Patients with steroid-refractory acute severe UC were randomized to cyclosporine (55 patients) or infliximab (56 patients). The researchers sought to determine whether treatment failure was less frequent with cyclosporine than with infliximab.

Adults were randomized if they were having a severe acute flare of UC (Lichtiger score greater than 10) and were refractory to intravenous steroid therapy (greater than or equal to 0.8 mg/kg per day of methylprednisone or equivalent) for at least 5 days. They had to be naive to the two treatment drugs and could not be under treatment with azathioprine/6-mercaptopurine unless therapy had been initiated fewer than 4 weeks before randomization.

The two groups were treated for up to 98 days, and the trial’s primary end point was treatment failure, defined as an absence of early clinical response, relapse after day 7, colectomy, absence of remission off steroids at the trial’s end, a severe adverse event, or death. Secondary end points included the Lichtiger score from day 0 to day 7, the percentage of patients showing clinical response at day 7, endoscopic response and colectomy at day 98, and the number of severe adverse events.

Approximately half the patients in both groups were female, with a median age of approximately 37 years, and had UC for at least 1 year. More than 90% of patients in both groups were naive to azathioprine. Lichtiger scores in both groups were 11 and over, and Mayo scores ranged from less than or equal to 0 to 12.

For the primary end point of treatment failure, 60% failed in the cyclosporine arm versus 54% in the infliximab arm, a nonsignificant difference.

The response rate at day 7 was 85.4% in the cyclosporine arm versus 85.7% in the infliximab arm, also not a significant difference. Response was defined as a Lichtiger score less than 10, and a decrease of at least 3 points compared with baseline.

The Lichtiger score from day 0 to day 6 showed that the median time to clinical response was 4 days (interquartile range [IQR], 3-6) with infliximab, versus 5 days (IQR, 4-7) for cyclosporine, a significant difference (P = .046).

At day 98, signs of mucosal healing were found in 52% of patients in the cyclosporine group and 53% of patients in the infliximab group. Healing was defined as having a Mayo endoscopic subscore of 0-1.

The colectomy rates were 18% in the cyclosporine arm and 21% in the infliximab arm. Severe adverse events affected 15% (8 patients) in the cyclosporine group and 25% (14 patients) in the infliximab group. Three patients developed cytomegalovirus colitis and two developed septicemia.

"In acute severe ulcerative colitis refractory to intravenous steroids, cyclosporine was not more effective than infliximab," said Dr. Laharie. "The short-term response was achieved with both drugs in more than 80% of patients within 1 week. Three-month colectomy rates were similar (18% with cyclosporine versus 21% with infliximab). And in this severe population, both drugs were well tolerated," he said.

Dr. Laharie disclosed financial relationships with Schering-Plough and Abbott Laboratories (royalty, speaking, and teaching), and with Norgine (consulting fee and board membership). The study received support from the Association François Aupetit, the Société Nationale Française de Gastro-Entérologie, and the International Organization for the Study of Inflammatory Bowel Disease, and was sponsored by Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.

CHICAGO – Eating bars rich in flaxseed failed to reduce hot flashes for postmenopausal women in a randomized, placebo-controlled, phase III trial conducted by the North Central Cancer Treatment Group.

Mean hot flash scores fell comparably in both arms of the study, which enrolled breast cancer patients and women who never had the disease. Instead of relief from this troubling symptom, many participants reported GI distress.

"Our findings do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were more likely due to the fiber content in the flaxseed and the placebo bars," said Dr. Sandhya Pruthi of the Mayo Clinic in Rochester, Minn. She presented the results at the annual meeting of the American Society of Clinical Oncology.

"Because hot flashes can negatively impact quality of life for many women, there is increasing interest in the use of complementary therapies such as flaxseed," Dr. Pruthi said, laying out the rationale for the trial.

Flaxseed is an annual plant, rich in lignans, which are a major class of phytoestrogens, she said. It is thought to have a weak estrogenlike effect, as well as estrogen antagonist effect.

In 2005, a pilot study of flaxseed was conducted in 30 women. They were given 400 mg of ground flaxseed, and investigators reported a 57% reduction in hot flash scores and a 50% reduction in hot flash frequency. This – along with a patient who claimed that flaxseed was successful in treating her hot flashes – led to the current trial, said Dr. Pruthi.

To be eligible, women with or without a history of breast cancer had to have more than 28 hot flashes per week. In all, 188 women were enrolled and 178 were randomized (88 to flaxseed bars containing 410 mg of lignans and fiber, and 90 to placebo bars containing protein and fiber, but no flaxseed, soy, or lignans). For 6 weeks, the participants were to eat one bar per day. The primary end point was a change from baseline in hot flash scores at week 6.

Of the entire group, 91 had a history of breast cancer but were without active disease. This group included women who were being treated with an aromatase inhibitor or tamoxifen.

Mean hot flash scores decreased by 4.9 units (about 33%) in the flaxseed arm, and 3.5 (about 29%) in the placebo arm (P = .29). "There was no significant difference in the reduction of hot flash scores between the two arms," said Dr. Pruthi.

No statistically significant toxicity was experienced by women in either arm, but both groups reported abdominal distention, gas, diarrhea, and nausea.

Although the results were disappointing, the trial does not leave women without remedies for hot flashes. Dr. Pruthi noted that venlafaxine and gabapentin were effective, and had been studied in randomized, placebo-controlled trials. "So we do have options for women who are not wanting to take hormonal therapies like estrogen or progesterone, especially with a history of breast cancer," she said.

"However, there are side effects with those drugs. Patients need to balance between treating their symptoms and managing their side effects, which is why we need to do more studies in other complementary therapies that we think might have [fewer side effects] and still give us the benefit of treating hot flashes," she said.

Dr. Pruthi reported having nothing to disclose. This study was funded by the National Cancer Institute.