Denosumab Not Cost Effective in Solid Tumor Bone Metastases

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.