Patient & Survivor Care

LONDON – Childhood cancer survivors face an increased risk of developing heart failure starting at a much younger age than the cardiac disease typically appears, according to a Dutch national cohort study.

“Health care professionals need to be aware of these findings and recognize the risk of developing heart failure in young people, even years after their childhood cancer treatment,” Dr. Elizabeth A.M. Feijen advised at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

She presented an analysis from the Dutch Childhood Oncology Group LATER (Late Effects of Childhood Cancer) study which entailed collecting followup data on more than 5,000 Dutch 5-year survivors of childhood cancer. After a median followup of 20 years, and at an average age of 27.4 years, 2% of the national cohort had been diagnosed with heart failure.

Of 113 childhood cancer survivors with heart failure, 9 had undergone heart transplantation, 11 required a pacemaker and/or implantable cardioverter-defibrillator, and 22 had died due to their heart failure, reported Dr. Feijen of the Academic Medical Center of Amsterdam.

The cumulative incidence of heart failure was 1.1% by age 20, 2.3% by age 30, 3.9% by age 40, and 5.4% by 50 years of age.

In a multivariate regression analysis, the significant risk factors for heart failure after childhood cancer were treatment with anthracyclines, with an associated 1.8-fold increased risk per 100 mg/m2 of medication; mitoxantrone, with a 2.3-fold risk per 25 mg/m2; chest radiation to the heart, with a 1.9-fold risk; and the use of cyclophosphamide, with an associated 1.8-fold increased risk of subsequent heart failure.

The DCOG LATER study is supported by the Dutch Cancer Society and the Children Cancer Free Foundation. Dr. Feijen reported having no financial conflicts.

[email protected]

LONDON – Childhood cancer survivors face an increased risk of developing heart failure starting at a much younger age than the cardiac disease typically appears, according to a Dutch national cohort study.

“Health care professionals need to be aware of these findings and recognize the risk of developing heart failure in young people, even years after their childhood cancer treatment,” Dr. Elizabeth A.M. Feijen advised at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

She presented an analysis from the Dutch Childhood Oncology Group LATER (Late Effects of Childhood Cancer) study which entailed collecting followup data on more than 5,000 Dutch 5-year survivors of childhood cancer. After a median followup of 20 years, and at an average age of 27.4 years, 2% of the national cohort had been diagnosed with heart failure.

Of 113 childhood cancer survivors with heart failure, 9 had undergone heart transplantation, 11 required a pacemaker and/or implantable cardioverter-defibrillator, and 22 had died due to their heart failure, reported Dr. Feijen of the Academic Medical Center of Amsterdam.

The cumulative incidence of heart failure was 1.1% by age 20, 2.3% by age 30, 3.9% by age 40, and 5.4% by 50 years of age.

In a multivariate regression analysis, the significant risk factors for heart failure after childhood cancer were treatment with anthracyclines, with an associated 1.8-fold increased risk per 100 mg/m2 of medication; mitoxantrone, with a 2.3-fold risk per 25 mg/m2; chest radiation to the heart, with a 1.9-fold risk; and the use of cyclophosphamide, with an associated 1.8-fold increased risk of subsequent heart failure.

The DCOG LATER study is supported by the Dutch Cancer Society and the Children Cancer Free Foundation. Dr. Feijen reported having no financial conflicts.

[email protected]

LONDON – Childhood cancer survivors face an increased risk of developing heart failure starting at a much younger age than the cardiac disease typically appears, according to a Dutch national cohort study.

“Health care professionals need to be aware of these findings and recognize the risk of developing heart failure in young people, even years after their childhood cancer treatment,” Dr. Elizabeth A.M. Feijen advised at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

She presented an analysis from the Dutch Childhood Oncology Group LATER (Late Effects of Childhood Cancer) study which entailed collecting followup data on more than 5,000 Dutch 5-year survivors of childhood cancer. After a median followup of 20 years, and at an average age of 27.4 years, 2% of the national cohort had been diagnosed with heart failure.

Of 113 childhood cancer survivors with heart failure, 9 had undergone heart transplantation, 11 required a pacemaker and/or implantable cardioverter-defibrillator, and 22 had died due to their heart failure, reported Dr. Feijen of the Academic Medical Center of Amsterdam.

The cumulative incidence of heart failure was 1.1% by age 20, 2.3% by age 30, 3.9% by age 40, and 5.4% by 50 years of age.

In a multivariate regression analysis, the significant risk factors for heart failure after childhood cancer were treatment with anthracyclines, with an associated 1.8-fold increased risk per 100 mg/m2 of medication; mitoxantrone, with a 2.3-fold risk per 25 mg/m2; chest radiation to the heart, with a 1.9-fold risk; and the use of cyclophosphamide, with an associated 1.8-fold increased risk of subsequent heart failure.

The DCOG LATER study is supported by the Dutch Cancer Society and the Children Cancer Free Foundation. Dr. Feijen reported having no financial conflicts.

[email protected]

DENVER – Anamorelin, an investigational compound that mimics the action of the so-called “hunger hormone” ghrelin, was effective at helping patients with cachexia gain weight, but fell short when it came to improving hand-grip strength, a surrogate for muscle mass, results of two clinical trials showed.

Among patients with advanced non–small cell lung cancer (NSCLC) and cachexia enrolled in two randomized clinical trials, those who took anamorelin daily over 12 weeks gained about 1 kg of lean body mass, compared with patients on placebo, who experienced further losses of lean body mass.

“Weight loss and loss of appetite are dominant symptoms in lung cancer patients, especially advanced lung cancer patients. About 70% experience this problem, and it’s something we hear in the clinic every day: Patients are frustrated and the family’s frustrated trying to get the patient to eat, but he or she can’t do it,” said investigator Dr. Philip Bonomi from Rush University Medical Center in Chicago.

He discussed results of the phase III ROMANA 1 and ROMANA 2 trials at a media briefing here at a world conference on lung cancer sponsored by the International Association for the Study of Lung Cancer.

Cachexia, defined as a loss of 5% or more of body weight over 6 months or a body mass index below 20 kg/m², is associated with poor clinical outcomes, including worse functional status, decreased quality of life, and shorter survival.

Anamorelin is an orally active selective ghrelin receptor agonist designed to mimic the hunger-inducing and anabolic effects of the natural hormone.

In the independent ROMANA 1 and ROMANA 2 trials, a total of 979 patients with unresectable stage III or IV NSCLC and cachexia were randomly assigned on a 2:1 basis to receive anamorelin 100 mg orally per day or placebo for 12 weeks.

For the coprimary endpoint of change in lean body mass patients assigned to anamorelin in ROMANA 1 (323 patients) had a median gain in lean body mass of 1.1 kg over 12 weeks, compared with a loss of 0.44 kg among 161 patients who received placebo (P less than .001)

In ROMANA 2, the 330 patients assigned to anamorelin gained a median of 0.75 kg, while the 165 assigned to placebo lost a median of 0.96 kg (P less than .001).

But for the other coprimary endpoint of improvement in hand-grip strength, patients in each arm of each trial lost strength over the 12 weeks, and there were no significant between-group differences, Dr. Bonomi said.

For the secondary endpoint of change in anorexia/cachexia domain of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire, patients who received anamorelin in each trial had significantly greater mean change from baseline in scores (4.12 vs. 1.92 for placebo in ROMANA 1; P = .0004: and 3.48 vs. 1.34 in ROMANA 2; P = .0016).

A prespecified exploratory-responder analysis also showed approximately twice as many patients treated with anamorelin maintained or gained lean body mass over the course of the study, compared with controls.

Regarding the failure of the drug to meet one of its primary endpoints, improvement of hand-grip strength as measure of gain in muscle mass, Dr. Bonomi said “Was it the right thing to measure? Many people think probably not, but nevertheless, there was no difference in hand-grip strength.”

He said that future studies should focus on whether therapies for cachexia can help improve patient’s physical functioning and activities of daily living.

DENVER – Anamorelin, an investigational compound that mimics the action of the so-called “hunger hormone” ghrelin, was effective at helping patients with cachexia gain weight, but fell short when it came to improving hand-grip strength, a surrogate for muscle mass, results of two clinical trials showed.

Among patients with advanced non–small cell lung cancer (NSCLC) and cachexia enrolled in two randomized clinical trials, those who took anamorelin daily over 12 weeks gained about 1 kg of lean body mass, compared with patients on placebo, who experienced further losses of lean body mass.

“Weight loss and loss of appetite are dominant symptoms in lung cancer patients, especially advanced lung cancer patients. About 70% experience this problem, and it’s something we hear in the clinic every day: Patients are frustrated and the family’s frustrated trying to get the patient to eat, but he or she can’t do it,” said investigator Dr. Philip Bonomi from Rush University Medical Center in Chicago.

He discussed results of the phase III ROMANA 1 and ROMANA 2 trials at a media briefing here at a world conference on lung cancer sponsored by the International Association for the Study of Lung Cancer.

Cachexia, defined as a loss of 5% or more of body weight over 6 months or a body mass index below 20 kg/m², is associated with poor clinical outcomes, including worse functional status, decreased quality of life, and shorter survival.

Anamorelin is an orally active selective ghrelin receptor agonist designed to mimic the hunger-inducing and anabolic effects of the natural hormone.

In the independent ROMANA 1 and ROMANA 2 trials, a total of 979 patients with unresectable stage III or IV NSCLC and cachexia were randomly assigned on a 2:1 basis to receive anamorelin 100 mg orally per day or placebo for 12 weeks.

For the coprimary endpoint of change in lean body mass patients assigned to anamorelin in ROMANA 1 (323 patients) had a median gain in lean body mass of 1.1 kg over 12 weeks, compared with a loss of 0.44 kg among 161 patients who received placebo (P less than .001)

In ROMANA 2, the 330 patients assigned to anamorelin gained a median of 0.75 kg, while the 165 assigned to placebo lost a median of 0.96 kg (P less than .001).

But for the other coprimary endpoint of improvement in hand-grip strength, patients in each arm of each trial lost strength over the 12 weeks, and there were no significant between-group differences, Dr. Bonomi said.

For the secondary endpoint of change in anorexia/cachexia domain of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire, patients who received anamorelin in each trial had significantly greater mean change from baseline in scores (4.12 vs. 1.92 for placebo in ROMANA 1; P = .0004: and 3.48 vs. 1.34 in ROMANA 2; P = .0016).

A prespecified exploratory-responder analysis also showed approximately twice as many patients treated with anamorelin maintained or gained lean body mass over the course of the study, compared with controls.

Regarding the failure of the drug to meet one of its primary endpoints, improvement of hand-grip strength as measure of gain in muscle mass, Dr. Bonomi said “Was it the right thing to measure? Many people think probably not, but nevertheless, there was no difference in hand-grip strength.”

He said that future studies should focus on whether therapies for cachexia can help improve patient’s physical functioning and activities of daily living.

DENVER – Anamorelin, an investigational compound that mimics the action of the so-called “hunger hormone” ghrelin, was effective at helping patients with cachexia gain weight, but fell short when it came to improving hand-grip strength, a surrogate for muscle mass, results of two clinical trials showed.

Among patients with advanced non–small cell lung cancer (NSCLC) and cachexia enrolled in two randomized clinical trials, those who took anamorelin daily over 12 weeks gained about 1 kg of lean body mass, compared with patients on placebo, who experienced further losses of lean body mass.

“Weight loss and loss of appetite are dominant symptoms in lung cancer patients, especially advanced lung cancer patients. About 70% experience this problem, and it’s something we hear in the clinic every day: Patients are frustrated and the family’s frustrated trying to get the patient to eat, but he or she can’t do it,” said investigator Dr. Philip Bonomi from Rush University Medical Center in Chicago.

He discussed results of the phase III ROMANA 1 and ROMANA 2 trials at a media briefing here at a world conference on lung cancer sponsored by the International Association for the Study of Lung Cancer.

Cachexia, defined as a loss of 5% or more of body weight over 6 months or a body mass index below 20 kg/m², is associated with poor clinical outcomes, including worse functional status, decreased quality of life, and shorter survival.

Anamorelin is an orally active selective ghrelin receptor agonist designed to mimic the hunger-inducing and anabolic effects of the natural hormone.

In the independent ROMANA 1 and ROMANA 2 trials, a total of 979 patients with unresectable stage III or IV NSCLC and cachexia were randomly assigned on a 2:1 basis to receive anamorelin 100 mg orally per day or placebo for 12 weeks.

For the coprimary endpoint of change in lean body mass patients assigned to anamorelin in ROMANA 1 (323 patients) had a median gain in lean body mass of 1.1 kg over 12 weeks, compared with a loss of 0.44 kg among 161 patients who received placebo (P less than .001)

In ROMANA 2, the 330 patients assigned to anamorelin gained a median of 0.75 kg, while the 165 assigned to placebo lost a median of 0.96 kg (P less than .001).

But for the other coprimary endpoint of improvement in hand-grip strength, patients in each arm of each trial lost strength over the 12 weeks, and there were no significant between-group differences, Dr. Bonomi said.

For the secondary endpoint of change in anorexia/cachexia domain of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire, patients who received anamorelin in each trial had significantly greater mean change from baseline in scores (4.12 vs. 1.92 for placebo in ROMANA 1; P = .0004: and 3.48 vs. 1.34 in ROMANA 2; P = .0016).

A prespecified exploratory-responder analysis also showed approximately twice as many patients treated with anamorelin maintained or gained lean body mass over the course of the study, compared with controls.

Regarding the failure of the drug to meet one of its primary endpoints, improvement of hand-grip strength as measure of gain in muscle mass, Dr. Bonomi said “Was it the right thing to measure? Many people think probably not, but nevertheless, there was no difference in hand-grip strength.”

He said that future studies should focus on whether therapies for cachexia can help improve patient’s physical functioning and activities of daily living.

In the past 50 years, the introductory cost of cancer drugs has risen over a hundred percent (adjusted for inflation), but Dr. Peter B. Bach wonders, “Are these drugs a hundred times better?”

To answer that question more definitively, Dr. Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, New York, and his colleagues have developed a proof of principal tool, the “Drug Abacus”.

The online tool uses a calculus of interactive algorithms that can be set by the individual to determine what a drug’s “true” price should be. Among the values possible to include are a drug’s risks, benefits, cost to develop and manufacture, and the life extension and quality of that extension that it offers. Also considered is how rare a disease is that a specific drug treats and how likely a drug will be able to help lift a public health burden. Although the drug abacus was developed to evaluate the cost of 54 cancer drugs, Dr. Bach believes the tool could be developed for use in evaluating the cost of any drug.

The drug abacus was designed for patients and policymakers alike, which Dr. Bach thinks could help bring about “value-generated prices and a transparent [pharmaceutical] marketplace.”

In a webinar sponsored by the University of Southern California’s Annenberg School for Journalism and the California Endowment for Health Journalism, Dr. Bach presented data from the past 20 years on the benefit of cancer drugs in terms of the survival gains between their time of introduction and their price per year of life gained. The data show that the inflation-adjusted cost for an additional life year earned by a cancer drug goes up by about $8,500. Speaking plainly, Dr. Bach said that means by 1995, buying a year of life cost about $50,000, whereas to do so in 2014 cost $250,000, adjusted for inflation.

“Maybe the drugs are somewhat better, but not enough to justify such a rise in cost,” Dr. Bach said.

In the case of the drug Blincyto (Amgen) approved by the FDA earlier this year to treat Philadelphia chromosome–negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL, the drug abacus cost is calculated as $7,946 when using the following variables: $12,000 for the cost per year added; a toxicity level of 30%; a novelty level of two out of three (it is the second-line FDA-approved therapy); a two out of three for cost of development; and a three out of three for rarity of disease treated. The actual cost of the treatment when it launched in the U.S. market in early 2015 was $64,260.

Were normal market conditions such as competition and demand driving the cost of drugs, Dr. Bach thinks drugs like the immunomodulator Gleevec (Novartis) would not be enjoying the exponential trajectory in revenues it has had since the FDA approved its new formulation in 2003: It has gone from costing an inflation-adjusted less than $100 per day for treatment to over $200. This, despite two other similar treatments (Tasigna, Novartis and Sprycel, Bristol-Myers Squibb) having entered the marketplace, and Gleevec having received multiple indications beyond its original use in leukemia.

“No one can look at this and say the market is working – either that the competition is lowering prices or that this is about recouping the cost of research and investment, Dr. Bach said.

A broken market means that people whose lives could be saved instead go without treatment, particularly if the cost to them is more than their insurance plan will cover, he said. Speaking about Gleevec, “nothing could be more frustrating than to have a drug that is essentially a cure be unavailable to patients because of a broken market.”

And yet, when the pharmaceutical industry does get pushed, interesting things can occur. In 2011, when Sanofi introduced the metastatic colon cancer drug Zaltrap, Dr. Bach and his colleagues at Sloan-Kettering refused to include it in their formulary citing comparative effectiveness data that did not justify its $11,000 per month price tag, double that of Avastin (Genentech) but with no clear additional benefit: Both drugs improved survival by about 6 weeks.

Sanofi immediately cut the cost of the drug in half nationwide.

“This told us two things,” says Dr. Bach. The first is that the market is indeed busted and the second is that there is immense power in comparative effectiveness research.

Thus was the genesis of the drug abacus, based largely on comparative effectiveness data. Dr. Bach said he thinks such “transparency of data” will help push back on pharmaceutical companies, empowering purchasers to outright refuse to pay arbitrary prices and bring about value-based prices and “rationalize this market.”

[email protected]

On Twitter @whitneymcknight

In the past 50 years, the introductory cost of cancer drugs has risen over a hundred percent (adjusted for inflation), but Dr. Peter B. Bach wonders, “Are these drugs a hundred times better?”

To answer that question more definitively, Dr. Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, New York, and his colleagues have developed a proof of principal tool, the “Drug Abacus”.

The online tool uses a calculus of interactive algorithms that can be set by the individual to determine what a drug’s “true” price should be. Among the values possible to include are a drug’s risks, benefits, cost to develop and manufacture, and the life extension and quality of that extension that it offers. Also considered is how rare a disease is that a specific drug treats and how likely a drug will be able to help lift a public health burden. Although the drug abacus was developed to evaluate the cost of 54 cancer drugs, Dr. Bach believes the tool could be developed for use in evaluating the cost of any drug.

The drug abacus was designed for patients and policymakers alike, which Dr. Bach thinks could help bring about “value-generated prices and a transparent [pharmaceutical] marketplace.”

In a webinar sponsored by the University of Southern California’s Annenberg School for Journalism and the California Endowment for Health Journalism, Dr. Bach presented data from the past 20 years on the benefit of cancer drugs in terms of the survival gains between their time of introduction and their price per year of life gained. The data show that the inflation-adjusted cost for an additional life year earned by a cancer drug goes up by about $8,500. Speaking plainly, Dr. Bach said that means by 1995, buying a year of life cost about $50,000, whereas to do so in 2014 cost $250,000, adjusted for inflation.

“Maybe the drugs are somewhat better, but not enough to justify such a rise in cost,” Dr. Bach said.

In the case of the drug Blincyto (Amgen) approved by the FDA earlier this year to treat Philadelphia chromosome–negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL, the drug abacus cost is calculated as $7,946 when using the following variables: $12,000 for the cost per year added; a toxicity level of 30%; a novelty level of two out of three (it is the second-line FDA-approved therapy); a two out of three for cost of development; and a three out of three for rarity of disease treated. The actual cost of the treatment when it launched in the U.S. market in early 2015 was $64,260.

Were normal market conditions such as competition and demand driving the cost of drugs, Dr. Bach thinks drugs like the immunomodulator Gleevec (Novartis) would not be enjoying the exponential trajectory in revenues it has had since the FDA approved its new formulation in 2003: It has gone from costing an inflation-adjusted less than $100 per day for treatment to over $200. This, despite two other similar treatments (Tasigna, Novartis and Sprycel, Bristol-Myers Squibb) having entered the marketplace, and Gleevec having received multiple indications beyond its original use in leukemia.

“No one can look at this and say the market is working – either that the competition is lowering prices or that this is about recouping the cost of research and investment, Dr. Bach said.

A broken market means that people whose lives could be saved instead go without treatment, particularly if the cost to them is more than their insurance plan will cover, he said. Speaking about Gleevec, “nothing could be more frustrating than to have a drug that is essentially a cure be unavailable to patients because of a broken market.”

And yet, when the pharmaceutical industry does get pushed, interesting things can occur. In 2011, when Sanofi introduced the metastatic colon cancer drug Zaltrap, Dr. Bach and his colleagues at Sloan-Kettering refused to include it in their formulary citing comparative effectiveness data that did not justify its $11,000 per month price tag, double that of Avastin (Genentech) but with no clear additional benefit: Both drugs improved survival by about 6 weeks.

Sanofi immediately cut the cost of the drug in half nationwide.

“This told us two things,” says Dr. Bach. The first is that the market is indeed busted and the second is that there is immense power in comparative effectiveness research.

Thus was the genesis of the drug abacus, based largely on comparative effectiveness data. Dr. Bach said he thinks such “transparency of data” will help push back on pharmaceutical companies, empowering purchasers to outright refuse to pay arbitrary prices and bring about value-based prices and “rationalize this market.”

[email protected]

On Twitter @whitneymcknight

In the past 50 years, the introductory cost of cancer drugs has risen over a hundred percent (adjusted for inflation), but Dr. Peter B. Bach wonders, “Are these drugs a hundred times better?”

To answer that question more definitively, Dr. Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, New York, and his colleagues have developed a proof of principal tool, the “Drug Abacus”.

The online tool uses a calculus of interactive algorithms that can be set by the individual to determine what a drug’s “true” price should be. Among the values possible to include are a drug’s risks, benefits, cost to develop and manufacture, and the life extension and quality of that extension that it offers. Also considered is how rare a disease is that a specific drug treats and how likely a drug will be able to help lift a public health burden. Although the drug abacus was developed to evaluate the cost of 54 cancer drugs, Dr. Bach believes the tool could be developed for use in evaluating the cost of any drug.

The drug abacus was designed for patients and policymakers alike, which Dr. Bach thinks could help bring about “value-generated prices and a transparent [pharmaceutical] marketplace.”

In a webinar sponsored by the University of Southern California’s Annenberg School for Journalism and the California Endowment for Health Journalism, Dr. Bach presented data from the past 20 years on the benefit of cancer drugs in terms of the survival gains between their time of introduction and their price per year of life gained. The data show that the inflation-adjusted cost for an additional life year earned by a cancer drug goes up by about $8,500. Speaking plainly, Dr. Bach said that means by 1995, buying a year of life cost about $50,000, whereas to do so in 2014 cost $250,000, adjusted for inflation.

“Maybe the drugs are somewhat better, but not enough to justify such a rise in cost,” Dr. Bach said.

In the case of the drug Blincyto (Amgen) approved by the FDA earlier this year to treat Philadelphia chromosome–negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL, the drug abacus cost is calculated as $7,946 when using the following variables: $12,000 for the cost per year added; a toxicity level of 30%; a novelty level of two out of three (it is the second-line FDA-approved therapy); a two out of three for cost of development; and a three out of three for rarity of disease treated. The actual cost of the treatment when it launched in the U.S. market in early 2015 was $64,260.

Were normal market conditions such as competition and demand driving the cost of drugs, Dr. Bach thinks drugs like the immunomodulator Gleevec (Novartis) would not be enjoying the exponential trajectory in revenues it has had since the FDA approved its new formulation in 2003: It has gone from costing an inflation-adjusted less than $100 per day for treatment to over $200. This, despite two other similar treatments (Tasigna, Novartis and Sprycel, Bristol-Myers Squibb) having entered the marketplace, and Gleevec having received multiple indications beyond its original use in leukemia.

“No one can look at this and say the market is working – either that the competition is lowering prices or that this is about recouping the cost of research and investment, Dr. Bach said.

A broken market means that people whose lives could be saved instead go without treatment, particularly if the cost to them is more than their insurance plan will cover, he said. Speaking about Gleevec, “nothing could be more frustrating than to have a drug that is essentially a cure be unavailable to patients because of a broken market.”

And yet, when the pharmaceutical industry does get pushed, interesting things can occur. In 2011, when Sanofi introduced the metastatic colon cancer drug Zaltrap, Dr. Bach and his colleagues at Sloan-Kettering refused to include it in their formulary citing comparative effectiveness data that did not justify its $11,000 per month price tag, double that of Avastin (Genentech) but with no clear additional benefit: Both drugs improved survival by about 6 weeks.

Sanofi immediately cut the cost of the drug in half nationwide.

“This told us two things,” says Dr. Bach. The first is that the market is indeed busted and the second is that there is immense power in comparative effectiveness research.

Thus was the genesis of the drug abacus, based largely on comparative effectiveness data. Dr. Bach said he thinks such “transparency of data” will help push back on pharmaceutical companies, empowering purchasers to outright refuse to pay arbitrary prices and bring about value-based prices and “rationalize this market.”

[email protected]

On Twitter @whitneymcknight

The Food and Drug Administration has approved rolapitant for use in adults undergoing initial and repeat courses of chemotherapy to prevent nausea and vomiting, and it can be used in combination with other antiemetic agents that patients are also taking.

The approval comes after three randomized, double-blind, controlled clinical trials in which 2,800 patients were given either rolapitant or a placebo in combination with granisetron and dexamethasone. All patients were already receiving a chemotherapy regimen of highly or moderately emetogenic chemotherapy drugs, such as cisplatin, anthracycline, and cyclophosphamide. Those taking rolapitant had significantly reduced rates of emesis than those in the control cohort.

The drug, marketed as Varubi by Waltham, Massachusetts–based Tesaro Inc., is taken in tablet form and acts as a substance P/neurokinin 1–receptor antagonist to block emesis caused by chemotherapy.

“Chemotherapy-induced nausea and vomiting remains a major issue that can disrupt patients’ lives and sometimes their therapy,” said Dr. Amy Egan, deputy director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research, in a statement. “Today’s approval provides cancer patients with another treatment option for the prevention of the delayed phase of nausea and vomiting caused by chemotherapy.”

Rolapitant is contraindicated for use with thioridazine, a drug which uses the CYP2D6 enzyme to metabolize – an enzyme which rolapitant inhibits. Taking both drugs together could cause arrhythmia. The most common side effects reported in patients taking rolapitant were neutropenia, decreased appetite, dizziness, and hiccups.

Serious adverse events associated with Varubi should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.

[email protected]

The Food and Drug Administration has approved rolapitant for use in adults undergoing initial and repeat courses of chemotherapy to prevent nausea and vomiting, and it can be used in combination with other antiemetic agents that patients are also taking.

The approval comes after three randomized, double-blind, controlled clinical trials in which 2,800 patients were given either rolapitant or a placebo in combination with granisetron and dexamethasone. All patients were already receiving a chemotherapy regimen of highly or moderately emetogenic chemotherapy drugs, such as cisplatin, anthracycline, and cyclophosphamide. Those taking rolapitant had significantly reduced rates of emesis than those in the control cohort.

The drug, marketed as Varubi by Waltham, Massachusetts–based Tesaro Inc., is taken in tablet form and acts as a substance P/neurokinin 1–receptor antagonist to block emesis caused by chemotherapy.

“Chemotherapy-induced nausea and vomiting remains a major issue that can disrupt patients’ lives and sometimes their therapy,” said Dr. Amy Egan, deputy director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research, in a statement. “Today’s approval provides cancer patients with another treatment option for the prevention of the delayed phase of nausea and vomiting caused by chemotherapy.”

Rolapitant is contraindicated for use with thioridazine, a drug which uses the CYP2D6 enzyme to metabolize – an enzyme which rolapitant inhibits. Taking both drugs together could cause arrhythmia. The most common side effects reported in patients taking rolapitant were neutropenia, decreased appetite, dizziness, and hiccups.

Serious adverse events associated with Varubi should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.

[email protected]

The Food and Drug Administration has approved rolapitant for use in adults undergoing initial and repeat courses of chemotherapy to prevent nausea and vomiting, and it can be used in combination with other antiemetic agents that patients are also taking.

The approval comes after three randomized, double-blind, controlled clinical trials in which 2,800 patients were given either rolapitant or a placebo in combination with granisetron and dexamethasone. All patients were already receiving a chemotherapy regimen of highly or moderately emetogenic chemotherapy drugs, such as cisplatin, anthracycline, and cyclophosphamide. Those taking rolapitant had significantly reduced rates of emesis than those in the control cohort.

The drug, marketed as Varubi by Waltham, Massachusetts–based Tesaro Inc., is taken in tablet form and acts as a substance P/neurokinin 1–receptor antagonist to block emesis caused by chemotherapy.

“Chemotherapy-induced nausea and vomiting remains a major issue that can disrupt patients’ lives and sometimes their therapy,” said Dr. Amy Egan, deputy director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research, in a statement. “Today’s approval provides cancer patients with another treatment option for the prevention of the delayed phase of nausea and vomiting caused by chemotherapy.”

Rolapitant is contraindicated for use with thioridazine, a drug which uses the CYP2D6 enzyme to metabolize – an enzyme which rolapitant inhibits. Taking both drugs together could cause arrhythmia. The most common side effects reported in patients taking rolapitant were neutropenia, decreased appetite, dizziness, and hiccups.

Serious adverse events associated with Varubi should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.

[email protected]

The Food and Drug Administration has issued an expanded indication for aprepitant (Emend) for the prevention of acute and delayed phases of chemotherapy-induced nausea and vomiting in patients 12-17 years old and in patients less than 12 years who weigh at least 66 lbs.

The approval is based on the results of a randomized, double-blind, active-comparator–controlled clinical study of 63 patients between 12 and 17 years of age, and 69 patients under the age of 12 years who weighed at least 66 pounds (30 kg). All patients were undergoing either highly or moderately emetogenic cancer chemotherapy and were put on a regimen of either ondansetron alone or ondensatron plus aprepitant, with intravenous dexamethasone administered at the physician’s discretion.

The primary outcome of no vomiting or retching and no use of rescue medication in the 25-120 hours following chemotherapy initiation was observed in 31 of 63 patients taking aprepitant plus ondensatron and in 13 of 69 patients taking ondensatron alone.

In the first 24 hours following chemotherapy initiation, 56% taking aprepitant plus ondensatron and 38% taking ondensatron alone achieved complete response. In the first 120 hours following chemotherapy initiation, 35% taking the combination and 13% taking ondensatron only had complete responses, according to a statement from Merck Research Laboratories.

Aprepitant is contraindicated for patients taking pimozide, as the CYP3A4 inhibitor in aprepitant can cause life-threatening, elevated plasma concentrations if taken with pimozide.

Serious adverse events associated with Emend should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.

[email protected]

The Food and Drug Administration has issued an expanded indication for aprepitant (Emend) for the prevention of acute and delayed phases of chemotherapy-induced nausea and vomiting in patients 12-17 years old and in patients less than 12 years who weigh at least 66 lbs.

The approval is based on the results of a randomized, double-blind, active-comparator–controlled clinical study of 63 patients between 12 and 17 years of age, and 69 patients under the age of 12 years who weighed at least 66 pounds (30 kg). All patients were undergoing either highly or moderately emetogenic cancer chemotherapy and were put on a regimen of either ondansetron alone or ondensatron plus aprepitant, with intravenous dexamethasone administered at the physician’s discretion.

The primary outcome of no vomiting or retching and no use of rescue medication in the 25-120 hours following chemotherapy initiation was observed in 31 of 63 patients taking aprepitant plus ondensatron and in 13 of 69 patients taking ondensatron alone.

In the first 24 hours following chemotherapy initiation, 56% taking aprepitant plus ondensatron and 38% taking ondensatron alone achieved complete response. In the first 120 hours following chemotherapy initiation, 35% taking the combination and 13% taking ondensatron only had complete responses, according to a statement from Merck Research Laboratories.

Aprepitant is contraindicated for patients taking pimozide, as the CYP3A4 inhibitor in aprepitant can cause life-threatening, elevated plasma concentrations if taken with pimozide.

Serious adverse events associated with Emend should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.

[email protected]

The Food and Drug Administration has issued an expanded indication for aprepitant (Emend) for the prevention of acute and delayed phases of chemotherapy-induced nausea and vomiting in patients 12-17 years old and in patients less than 12 years who weigh at least 66 lbs.

The approval is based on the results of a randomized, double-blind, active-comparator–controlled clinical study of 63 patients between 12 and 17 years of age, and 69 patients under the age of 12 years who weighed at least 66 pounds (30 kg). All patients were undergoing either highly or moderately emetogenic cancer chemotherapy and were put on a regimen of either ondansetron alone or ondensatron plus aprepitant, with intravenous dexamethasone administered at the physician’s discretion.

The primary outcome of no vomiting or retching and no use of rescue medication in the 25-120 hours following chemotherapy initiation was observed in 31 of 63 patients taking aprepitant plus ondensatron and in 13 of 69 patients taking ondensatron alone.

In the first 24 hours following chemotherapy initiation, 56% taking aprepitant plus ondensatron and 38% taking ondensatron alone achieved complete response. In the first 120 hours following chemotherapy initiation, 35% taking the combination and 13% taking ondensatron only had complete responses, according to a statement from Merck Research Laboratories.

Aprepitant is contraindicated for patients taking pimozide, as the CYP3A4 inhibitor in aprepitant can cause life-threatening, elevated plasma concentrations if taken with pimozide.

Serious adverse events associated with Emend should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/Safety/MedWatch/default.htm.

[email protected]

NEW YORK – Due to the frequency with which patients develop pruritus while on a targeted cancer therapy, prophylaxis should be strongly considered for at least some of the drugs, such as epidermal growth factor–receptor (EGFR) inhibitors, according to an expert in oncodermatology.

“Pruritus is a frequent adverse event in cancer patients treated with targeted therapies and an early and proactive approach towards pruritus is advisable,” Dr. Mario E. Lacouture, director of the oncodermatology program at New York’s Memorial Sloan Kettering Cancer Center. The increasing use of targeted therapies, including the growing proportion of patients on long-term maintenance regimens, is expected to make these complaints more common.

Targeted cancer therapies, such as monoclonal antibodies and tyrosine kinase inhibitors (TKIs), are, in general, associated with a low risk of adverse events relative to cytotoxic chemotherapies. The exception is dermatologic adverse events, Dr. Lacouture said at the American Academy of Dermatology summer meeting. Skin rashes are characteristic adverse events with several targeted agents, such as the EGFR inhibitor cetuximab, but Dr. Lacouture warned that pruritus for many patients imposes the greatest burden.

“Since the introduction of the first targeted cancer drug, imatinib, in 2001, a long list of targeted agents have been approved, and all are associated with pruritus that significantly reduces quality of life,” he reported. Dermatologists need to fill a void.

“Oncologists are not generally familiar with strategies to treat pruritus and typically resort to antihistamines, such as diphenhydramine or hydroxyzine,” Dr. Lacouture added. He suggested such sedative agents “are not ideal” when managing an adverse event that may persist for weeks or months.

The first step may simply be to prepare patients initiating targeted therapy for the substantial risk of pruritus. Dr. Lacouture cited two studies in which cancer patients were asked about unexpected side effects. In both, dermatologic complaints were the most common.

“Patients are told that they are going to lose their hair, that they are going to have nausea and vomiting, but they are never told that they are going to have dry skin, irritated skin, or itchy skin,” Dr. Lacouture noted. He cited one study in which all three of the top side effects identified by cancer patients as unexpected were dermatologic, including nail changes and pruritus.

In fact, published studies suggest that most patients treated with EGFR inhibitors, and approximately one-third of patients treated with a variety of TKIs, such as those targeting BRAF and MEK pathways, will develop significant pruritus, according to Dr. Lacouture. However, several studies, including one of his own, suggest that this itching can be greatly mitigated not only by treatment but also with prophylaxis.

In his study of the effect of prophylaxis, 95 patients initiating the EGFR inhibitor panitumumab were randomized to a prophylactic regimen that included skin moisturizers, sunscreen, a topical steroid, and doxycycline, or to treatment adjusted for symptoms once they developed (J Clin Oncol. 2010;28:1351-7). At 6 weeks, the proportion of patients with grade 2 or higher dermatologic events, including pruritus, was reduced from 62% to 29%. More favorable quality of life scores in the prophylactic regimen group supported the advantage.

“When you looked at grade 3 or higher adverse events, you see that the incidence of acneiform rash [at the grade 3 level of severity] was lowered by almost 75% and pruritus was almost abolished,” Dr. Lacouture reported.

For refractory pruritus related to targeted therapy, aprepitant may be the best option based on Dr. Lacouture’s own experience and a prospective but nonrandomized study (Lancet Oncol. 2012;13:1020-4). In the published study, which included patients on EGFR inhibitors or TKIs, the median visual analog scores (VAS) for pruritus fell from 8 before treatment to 1, 1 week later. According to Dr. Lacouture, the treatment effects are durable. In some cases, pruritus does not recur even after a single course of aprepitant.

“The importance of pruritus in the cancer population is going to increase as targeted therapies enter the adjuvant setting,” Dr. Lacouture remarked. Also important, patients on targeted therapies are living longer, “and as patients live longer, more attention is being placed on quality of life issues of which pruritus is one of the topmost concerns.”

Dr. Lacouture reports financial relationships with Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Foamix, Galderma Laboratories, Hana Biosciences, Imclone, Merck Serono, Novartis, Novocure, OSI Pharma, Pfizer, Pierre Fabre Dermatologie, Reata Pharmaceuticals, Roche Laboratories, Threshold Pharmaceuticals, and Vertex Pharmaceuticals.

NEW YORK – Due to the frequency with which patients develop pruritus while on a targeted cancer therapy, prophylaxis should be strongly considered for at least some of the drugs, such as epidermal growth factor–receptor (EGFR) inhibitors, according to an expert in oncodermatology.

“Pruritus is a frequent adverse event in cancer patients treated with targeted therapies and an early and proactive approach towards pruritus is advisable,” Dr. Mario E. Lacouture, director of the oncodermatology program at New York’s Memorial Sloan Kettering Cancer Center. The increasing use of targeted therapies, including the growing proportion of patients on long-term maintenance regimens, is expected to make these complaints more common.

Targeted cancer therapies, such as monoclonal antibodies and tyrosine kinase inhibitors (TKIs), are, in general, associated with a low risk of adverse events relative to cytotoxic chemotherapies. The exception is dermatologic adverse events, Dr. Lacouture said at the American Academy of Dermatology summer meeting. Skin rashes are characteristic adverse events with several targeted agents, such as the EGFR inhibitor cetuximab, but Dr. Lacouture warned that pruritus for many patients imposes the greatest burden.

“Since the introduction of the first targeted cancer drug, imatinib, in 2001, a long list of targeted agents have been approved, and all are associated with pruritus that significantly reduces quality of life,” he reported. Dermatologists need to fill a void.

“Oncologists are not generally familiar with strategies to treat pruritus and typically resort to antihistamines, such as diphenhydramine or hydroxyzine,” Dr. Lacouture added. He suggested such sedative agents “are not ideal” when managing an adverse event that may persist for weeks or months.

The first step may simply be to prepare patients initiating targeted therapy for the substantial risk of pruritus. Dr. Lacouture cited two studies in which cancer patients were asked about unexpected side effects. In both, dermatologic complaints were the most common.

“Patients are told that they are going to lose their hair, that they are going to have nausea and vomiting, but they are never told that they are going to have dry skin, irritated skin, or itchy skin,” Dr. Lacouture noted. He cited one study in which all three of the top side effects identified by cancer patients as unexpected were dermatologic, including nail changes and pruritus.

In fact, published studies suggest that most patients treated with EGFR inhibitors, and approximately one-third of patients treated with a variety of TKIs, such as those targeting BRAF and MEK pathways, will develop significant pruritus, according to Dr. Lacouture. However, several studies, including one of his own, suggest that this itching can be greatly mitigated not only by treatment but also with prophylaxis.

In his study of the effect of prophylaxis, 95 patients initiating the EGFR inhibitor panitumumab were randomized to a prophylactic regimen that included skin moisturizers, sunscreen, a topical steroid, and doxycycline, or to treatment adjusted for symptoms once they developed (J Clin Oncol. 2010;28:1351-7). At 6 weeks, the proportion of patients with grade 2 or higher dermatologic events, including pruritus, was reduced from 62% to 29%. More favorable quality of life scores in the prophylactic regimen group supported the advantage.

“When you looked at grade 3 or higher adverse events, you see that the incidence of acneiform rash [at the grade 3 level of severity] was lowered by almost 75% and pruritus was almost abolished,” Dr. Lacouture reported.

For refractory pruritus related to targeted therapy, aprepitant may be the best option based on Dr. Lacouture’s own experience and a prospective but nonrandomized study (Lancet Oncol. 2012;13:1020-4). In the published study, which included patients on EGFR inhibitors or TKIs, the median visual analog scores (VAS) for pruritus fell from 8 before treatment to 1, 1 week later. According to Dr. Lacouture, the treatment effects are durable. In some cases, pruritus does not recur even after a single course of aprepitant.

“The importance of pruritus in the cancer population is going to increase as targeted therapies enter the adjuvant setting,” Dr. Lacouture remarked. Also important, patients on targeted therapies are living longer, “and as patients live longer, more attention is being placed on quality of life issues of which pruritus is one of the topmost concerns.”

Dr. Lacouture reports financial relationships with Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Foamix, Galderma Laboratories, Hana Biosciences, Imclone, Merck Serono, Novartis, Novocure, OSI Pharma, Pfizer, Pierre Fabre Dermatologie, Reata Pharmaceuticals, Roche Laboratories, Threshold Pharmaceuticals, and Vertex Pharmaceuticals.

NEW YORK – Due to the frequency with which patients develop pruritus while on a targeted cancer therapy, prophylaxis should be strongly considered for at least some of the drugs, such as epidermal growth factor–receptor (EGFR) inhibitors, according to an expert in oncodermatology.

“Pruritus is a frequent adverse event in cancer patients treated with targeted therapies and an early and proactive approach towards pruritus is advisable,” Dr. Mario E. Lacouture, director of the oncodermatology program at New York’s Memorial Sloan Kettering Cancer Center. The increasing use of targeted therapies, including the growing proportion of patients on long-term maintenance regimens, is expected to make these complaints more common.

Targeted cancer therapies, such as monoclonal antibodies and tyrosine kinase inhibitors (TKIs), are, in general, associated with a low risk of adverse events relative to cytotoxic chemotherapies. The exception is dermatologic adverse events, Dr. Lacouture said at the American Academy of Dermatology summer meeting. Skin rashes are characteristic adverse events with several targeted agents, such as the EGFR inhibitor cetuximab, but Dr. Lacouture warned that pruritus for many patients imposes the greatest burden.

“Since the introduction of the first targeted cancer drug, imatinib, in 2001, a long list of targeted agents have been approved, and all are associated with pruritus that significantly reduces quality of life,” he reported. Dermatologists need to fill a void.

“Oncologists are not generally familiar with strategies to treat pruritus and typically resort to antihistamines, such as diphenhydramine or hydroxyzine,” Dr. Lacouture added. He suggested such sedative agents “are not ideal” when managing an adverse event that may persist for weeks or months.

The first step may simply be to prepare patients initiating targeted therapy for the substantial risk of pruritus. Dr. Lacouture cited two studies in which cancer patients were asked about unexpected side effects. In both, dermatologic complaints were the most common.

“Patients are told that they are going to lose their hair, that they are going to have nausea and vomiting, but they are never told that they are going to have dry skin, irritated skin, or itchy skin,” Dr. Lacouture noted. He cited one study in which all three of the top side effects identified by cancer patients as unexpected were dermatologic, including nail changes and pruritus.

In fact, published studies suggest that most patients treated with EGFR inhibitors, and approximately one-third of patients treated with a variety of TKIs, such as those targeting BRAF and MEK pathways, will develop significant pruritus, according to Dr. Lacouture. However, several studies, including one of his own, suggest that this itching can be greatly mitigated not only by treatment but also with prophylaxis.

In his study of the effect of prophylaxis, 95 patients initiating the EGFR inhibitor panitumumab were randomized to a prophylactic regimen that included skin moisturizers, sunscreen, a topical steroid, and doxycycline, or to treatment adjusted for symptoms once they developed (J Clin Oncol. 2010;28:1351-7). At 6 weeks, the proportion of patients with grade 2 or higher dermatologic events, including pruritus, was reduced from 62% to 29%. More favorable quality of life scores in the prophylactic regimen group supported the advantage.

“When you looked at grade 3 or higher adverse events, you see that the incidence of acneiform rash [at the grade 3 level of severity] was lowered by almost 75% and pruritus was almost abolished,” Dr. Lacouture reported.

For refractory pruritus related to targeted therapy, aprepitant may be the best option based on Dr. Lacouture’s own experience and a prospective but nonrandomized study (Lancet Oncol. 2012;13:1020-4). In the published study, which included patients on EGFR inhibitors or TKIs, the median visual analog scores (VAS) for pruritus fell from 8 before treatment to 1, 1 week later. According to Dr. Lacouture, the treatment effects are durable. In some cases, pruritus does not recur even after a single course of aprepitant.

“The importance of pruritus in the cancer population is going to increase as targeted therapies enter the adjuvant setting,” Dr. Lacouture remarked. Also important, patients on targeted therapies are living longer, “and as patients live longer, more attention is being placed on quality of life issues of which pruritus is one of the topmost concerns.”

Dr. Lacouture reports financial relationships with Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Foamix, Galderma Laboratories, Hana Biosciences, Imclone, Merck Serono, Novartis, Novocure, OSI Pharma, Pfizer, Pierre Fabre Dermatologie, Reata Pharmaceuticals, Roche Laboratories, Threshold Pharmaceuticals, and Vertex Pharmaceuticals.

WASHINGTON – Chalk up one for the little guy: Community cancer programs are better equipped for delivering psychosocial support services than are National Cancer Institute–designated Cancer Programs, investigators contend.

A survey conducted by oncology social workers in 60 large and small cancer programs across North America reveals that significantly more community cancer centers have comprehensive systems in place for screening, assessing, and managing the psychosocial needs of patients with cancer, said Dr. Brad Zebrack from the University of Michigan School of Social Work in Ann Arbor.

“We still have work to do in terms of monitoring quality of care on a systemwide level. There’s still room [for improvement in] educating providers about the value and the importance of psychosocial care, and a lot of work to do in overcoming the observed racial disparities that we’re seeing in the provision of care,” he said at the at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Dr. Zebrack reported results of APAQCC (“A Project to Assure Quality Cancer Care”), a multisite study looking at institutional capacity to provide psychosocial services as a function of patient, provider, and institutional characteristics.

The investigators enlisted the help of oncology social workers at 60 accredited cancer programs, including comprehensive cancer center programs, community cancer programs (CCPs), NCI-designated cancer programs (NCIPs), and nondesignated academic medical center–based programs. The social workers administered the 10-item NCI Psychosocial Matrix to a convenience sample of providers at their centers.

The matrix assesses capacity to provide psychosocial services on a scale of 1-5, with 1 signaling that no systematic process is in place, and 5 indicating optimal implementation. The matrix includes 10 items concerning provider-patient communications, patient-needs assessments, care planning and coordination, provider training and education, evaluation of service delivery and patient outcomes, and quality improvement.

A total of 2,491 professionals responded. The sample comprised primary- or mid-level providers, nurses, psychosocial care providers, ancillary care providers, and administrators or managers not directly involved in patient care.

They found that respondents from NCIPs consistently reported significantly lower levels of capacity. For example, 36% of NCIPs reported having multiple mechanisms and multiple opportunities for communicating to cancer patients and their families the importance of psychosocial needs and care, and 47% reported that they communicated about psychosocial care by at least one mechanism at least one time. In contrast, the respective percentages for CCPs were 46% and 51%. In all, 17% of NCIPs had a failing grade on communication, compared with just 3% of CCPs.

CCPs were also better at identifying psychosocial health needs of cancer patients (37% reported the highest level of assessments, and 34% reported at least screening and assessment, compared with 20% and 29% for NCIPs).

Continuity of psychosocial care, measured as the capacity to conduct follow-up, reevaluation, and adjustment of a psychosocial treatment plan, was also highest at CCPs and lowest at NCIPs (30% vs. 18%).

In an analysis of capacity by provider type, the authors found that hospitals with a greater than 30% racial minority population had significantly lower capacity to communicate the importance of psychosocial care (P less than .05). In an analysis by program type, NCIPs were also worse at communicating these ideas than other program types (P less than .05).

Their findings suggest that assessing institutional capacity, monitoring changes in services, and tracking patient outcomes will be required for improvement of the delivery of psychosocial services in cancer programs of all types, Dr. Zebrack said.

The study is supported by the Association of Oncology Social Work with an educational grant from Takeda Oncology. The authors reported having no conflicts of interest.

WASHINGTON – Chalk up one for the little guy: Community cancer programs are better equipped for delivering psychosocial support services than are National Cancer Institute–designated Cancer Programs, investigators contend.

A survey conducted by oncology social workers in 60 large and small cancer programs across North America reveals that significantly more community cancer centers have comprehensive systems in place for screening, assessing, and managing the psychosocial needs of patients with cancer, said Dr. Brad Zebrack from the University of Michigan School of Social Work in Ann Arbor.

“We still have work to do in terms of monitoring quality of care on a systemwide level. There’s still room [for improvement in] educating providers about the value and the importance of psychosocial care, and a lot of work to do in overcoming the observed racial disparities that we’re seeing in the provision of care,” he said at the at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Dr. Zebrack reported results of APAQCC (“A Project to Assure Quality Cancer Care”), a multisite study looking at institutional capacity to provide psychosocial services as a function of patient, provider, and institutional characteristics.

The investigators enlisted the help of oncology social workers at 60 accredited cancer programs, including comprehensive cancer center programs, community cancer programs (CCPs), NCI-designated cancer programs (NCIPs), and nondesignated academic medical center–based programs. The social workers administered the 10-item NCI Psychosocial Matrix to a convenience sample of providers at their centers.

The matrix assesses capacity to provide psychosocial services on a scale of 1-5, with 1 signaling that no systematic process is in place, and 5 indicating optimal implementation. The matrix includes 10 items concerning provider-patient communications, patient-needs assessments, care planning and coordination, provider training and education, evaluation of service delivery and patient outcomes, and quality improvement.

A total of 2,491 professionals responded. The sample comprised primary- or mid-level providers, nurses, psychosocial care providers, ancillary care providers, and administrators or managers not directly involved in patient care.

They found that respondents from NCIPs consistently reported significantly lower levels of capacity. For example, 36% of NCIPs reported having multiple mechanisms and multiple opportunities for communicating to cancer patients and their families the importance of psychosocial needs and care, and 47% reported that they communicated about psychosocial care by at least one mechanism at least one time. In contrast, the respective percentages for CCPs were 46% and 51%. In all, 17% of NCIPs had a failing grade on communication, compared with just 3% of CCPs.

CCPs were also better at identifying psychosocial health needs of cancer patients (37% reported the highest level of assessments, and 34% reported at least screening and assessment, compared with 20% and 29% for NCIPs).

Continuity of psychosocial care, measured as the capacity to conduct follow-up, reevaluation, and adjustment of a psychosocial treatment plan, was also highest at CCPs and lowest at NCIPs (30% vs. 18%).

In an analysis of capacity by provider type, the authors found that hospitals with a greater than 30% racial minority population had significantly lower capacity to communicate the importance of psychosocial care (P less than .05). In an analysis by program type, NCIPs were also worse at communicating these ideas than other program types (P less than .05).

Their findings suggest that assessing institutional capacity, monitoring changes in services, and tracking patient outcomes will be required for improvement of the delivery of psychosocial services in cancer programs of all types, Dr. Zebrack said.

The study is supported by the Association of Oncology Social Work with an educational grant from Takeda Oncology. The authors reported having no conflicts of interest.

WASHINGTON – Chalk up one for the little guy: Community cancer programs are better equipped for delivering psychosocial support services than are National Cancer Institute–designated Cancer Programs, investigators contend.

A survey conducted by oncology social workers in 60 large and small cancer programs across North America reveals that significantly more community cancer centers have comprehensive systems in place for screening, assessing, and managing the psychosocial needs of patients with cancer, said Dr. Brad Zebrack from the University of Michigan School of Social Work in Ann Arbor.

“We still have work to do in terms of monitoring quality of care on a systemwide level. There’s still room [for improvement in] educating providers about the value and the importance of psychosocial care, and a lot of work to do in overcoming the observed racial disparities that we’re seeing in the provision of care,” he said at the at the joint congress of the International Psycho-Oncology Society and the American Psychosocial Oncology Society.

Dr. Zebrack reported results of APAQCC (“A Project to Assure Quality Cancer Care”), a multisite study looking at institutional capacity to provide psychosocial services as a function of patient, provider, and institutional characteristics.

The investigators enlisted the help of oncology social workers at 60 accredited cancer programs, including comprehensive cancer center programs, community cancer programs (CCPs), NCI-designated cancer programs (NCIPs), and nondesignated academic medical center–based programs. The social workers administered the 10-item NCI Psychosocial Matrix to a convenience sample of providers at their centers.

The matrix assesses capacity to provide psychosocial services on a scale of 1-5, with 1 signaling that no systematic process is in place, and 5 indicating optimal implementation. The matrix includes 10 items concerning provider-patient communications, patient-needs assessments, care planning and coordination, provider training and education, evaluation of service delivery and patient outcomes, and quality improvement.

A total of 2,491 professionals responded. The sample comprised primary- or mid-level providers, nurses, psychosocial care providers, ancillary care providers, and administrators or managers not directly involved in patient care.

They found that respondents from NCIPs consistently reported significantly lower levels of capacity. For example, 36% of NCIPs reported having multiple mechanisms and multiple opportunities for communicating to cancer patients and their families the importance of psychosocial needs and care, and 47% reported that they communicated about psychosocial care by at least one mechanism at least one time. In contrast, the respective percentages for CCPs were 46% and 51%. In all, 17% of NCIPs had a failing grade on communication, compared with just 3% of CCPs.

CCPs were also better at identifying psychosocial health needs of cancer patients (37% reported the highest level of assessments, and 34% reported at least screening and assessment, compared with 20% and 29% for NCIPs).

Continuity of psychosocial care, measured as the capacity to conduct follow-up, reevaluation, and adjustment of a psychosocial treatment plan, was also highest at CCPs and lowest at NCIPs (30% vs. 18%).

In an analysis of capacity by provider type, the authors found that hospitals with a greater than 30% racial minority population had significantly lower capacity to communicate the importance of psychosocial care (P less than .05). In an analysis by program type, NCIPs were also worse at communicating these ideas than other program types (P less than .05).

Their findings suggest that assessing institutional capacity, monitoring changes in services, and tracking patient outcomes will be required for improvement of the delivery of psychosocial services in cancer programs of all types, Dr. Zebrack said.

The study is supported by the Association of Oncology Social Work with an educational grant from Takeda Oncology. The authors reported having no conflicts of interest.

Cancer patients who arrive in the emergency department with febrile neutropenia (FN) received antibiotics much more quickly when their condition was identified as a medical emergency and a care pathway was used to guide treatment. The set of simple interventions slashed average time to antibiotics from about 4 hours to less than 1.5 hours, compared with a historical cohort, and the inexpensive interventions have had durable results.

Dr. Michael Keng and his coinvestigators at the Cleveland Clinic reported the results of a single-center prospective analysis that targeted FN, a common and serious chemotherapy complication with a mortality rate that can exceed 50% in medically fragile individuals [doi:10.1200/JOP.2014.002733].

“With an increasing number of outpatient chemotherapy regimens, more patients are likely to present to the emergency department (ED) with FN,” wrote Dr. Keng. The FN pathway devised by Dr. Keng and his associates implemented key changes designed to identify FN as an emergency and guide prompt triage, assessment, and treatment.

Study coauthor Dr. Mikkael Sekeres said, “The interventions were not complicated. We standardized our definition of fever; provided patients with wallet-sized cards alerting emergency departments to the potential of this serious condition; worked with our emergency department staff to change the triage level of fever and neutropenia to be equivalent to that observed for heart attack or stroke; designed standard febrile neutropenia order sets for our electronic medical record; and relocated the antibiotics used to treat febrile neutropenia to our emergency department.”

Febrile patients with cancer in the prospective cohort (n = 223) were compared with a historical cohort of patients presenting to the ED who received usual care (n = 87), as well as to a concurrent cohort of patients who were directly admitted to the hospital (n = 114). The total number of FN episodes for the cohorts was 276, 107, and 114, respectively. Multivariable analysis was used to account for some differences in patient characteristics across cohorts.

Time to antibiotics for the pathway was a median 81 minutes, compared with 225 minutes for the historical cohort and 169 minutes for the direct-admission cohort (P less than .001 for both). Only two patients in the combined comparison cohorts received antibiotics within 60 minutes, while almost one-third of the prospective cohort receiving the protocol was treated within 60 minutes.

Using the order set in the EHR also made a difference: for those treated per the order set (n = 103), median time to antibiotics was 68 minutes, compared with 96 minutes when the order set was not used.

Secondary outcome measures included times to physician assessment, blood draw, and antibiotic order placement. All measures except time to physician assessment were significantly shorter for the FN pathway group than for the comparison cohorts (P less than .001 for all).

Since so many changes were made at once, Dr. Keng and his coauthors noted, “it is difficult to determine the impact of any one change.” Some institutions may have difficulty implementing all the interventions, but immediate triage, automated antibiotic ordering, and EHR use were the changes that had the most impact, he wrote.

“Instituting these changes took less than half a year, and the benefits have persisted for years afterward,” Dr. Sekeres said in an interview.

No study authors reported conflicts of interest.

[email protected]

Cancer patients who arrive in the emergency department with febrile neutropenia (FN) received antibiotics much more quickly when their condition was identified as a medical emergency and a care pathway was used to guide treatment. The set of simple interventions slashed average time to antibiotics from about 4 hours to less than 1.5 hours, compared with a historical cohort, and the inexpensive interventions have had durable results.

Dr. Michael Keng and his coinvestigators at the Cleveland Clinic reported the results of a single-center prospective analysis that targeted FN, a common and serious chemotherapy complication with a mortality rate that can exceed 50% in medically fragile individuals [doi:10.1200/JOP.2014.002733].

“With an increasing number of outpatient chemotherapy regimens, more patients are likely to present to the emergency department (ED) with FN,” wrote Dr. Keng. The FN pathway devised by Dr. Keng and his associates implemented key changes designed to identify FN as an emergency and guide prompt triage, assessment, and treatment.

Study coauthor Dr. Mikkael Sekeres said, “The interventions were not complicated. We standardized our definition of fever; provided patients with wallet-sized cards alerting emergency departments to the potential of this serious condition; worked with our emergency department staff to change the triage level of fever and neutropenia to be equivalent to that observed for heart attack or stroke; designed standard febrile neutropenia order sets for our electronic medical record; and relocated the antibiotics used to treat febrile neutropenia to our emergency department.”

Febrile patients with cancer in the prospective cohort (n = 223) were compared with a historical cohort of patients presenting to the ED who received usual care (n = 87), as well as to a concurrent cohort of patients who were directly admitted to the hospital (n = 114). The total number of FN episodes for the cohorts was 276, 107, and 114, respectively. Multivariable analysis was used to account for some differences in patient characteristics across cohorts.

Time to antibiotics for the pathway was a median 81 minutes, compared with 225 minutes for the historical cohort and 169 minutes for the direct-admission cohort (P less than .001 for both). Only two patients in the combined comparison cohorts received antibiotics within 60 minutes, while almost one-third of the prospective cohort receiving the protocol was treated within 60 minutes.

Using the order set in the EHR also made a difference: for those treated per the order set (n = 103), median time to antibiotics was 68 minutes, compared with 96 minutes when the order set was not used.

Secondary outcome measures included times to physician assessment, blood draw, and antibiotic order placement. All measures except time to physician assessment were significantly shorter for the FN pathway group than for the comparison cohorts (P less than .001 for all).

Since so many changes were made at once, Dr. Keng and his coauthors noted, “it is difficult to determine the impact of any one change.” Some institutions may have difficulty implementing all the interventions, but immediate triage, automated antibiotic ordering, and EHR use were the changes that had the most impact, he wrote.

“Instituting these changes took less than half a year, and the benefits have persisted for years afterward,” Dr. Sekeres said in an interview.

No study authors reported conflicts of interest.

[email protected]

Cancer patients who arrive in the emergency department with febrile neutropenia (FN) received antibiotics much more quickly when their condition was identified as a medical emergency and a care pathway was used to guide treatment. The set of simple interventions slashed average time to antibiotics from about 4 hours to less than 1.5 hours, compared with a historical cohort, and the inexpensive interventions have had durable results.

Dr. Michael Keng and his coinvestigators at the Cleveland Clinic reported the results of a single-center prospective analysis that targeted FN, a common and serious chemotherapy complication with a mortality rate that can exceed 50% in medically fragile individuals [doi:10.1200/JOP.2014.002733].

“With an increasing number of outpatient chemotherapy regimens, more patients are likely to present to the emergency department (ED) with FN,” wrote Dr. Keng. The FN pathway devised by Dr. Keng and his associates implemented key changes designed to identify FN as an emergency and guide prompt triage, assessment, and treatment.

Study coauthor Dr. Mikkael Sekeres said, “The interventions were not complicated. We standardized our definition of fever; provided patients with wallet-sized cards alerting emergency departments to the potential of this serious condition; worked with our emergency department staff to change the triage level of fever and neutropenia to be equivalent to that observed for heart attack or stroke; designed standard febrile neutropenia order sets for our electronic medical record; and relocated the antibiotics used to treat febrile neutropenia to our emergency department.”

Febrile patients with cancer in the prospective cohort (n = 223) were compared with a historical cohort of patients presenting to the ED who received usual care (n = 87), as well as to a concurrent cohort of patients who were directly admitted to the hospital (n = 114). The total number of FN episodes for the cohorts was 276, 107, and 114, respectively. Multivariable analysis was used to account for some differences in patient characteristics across cohorts.

Time to antibiotics for the pathway was a median 81 minutes, compared with 225 minutes for the historical cohort and 169 minutes for the direct-admission cohort (P less than .001 for both). Only two patients in the combined comparison cohorts received antibiotics within 60 minutes, while almost one-third of the prospective cohort receiving the protocol was treated within 60 minutes.

Using the order set in the EHR also made a difference: for those treated per the order set (n = 103), median time to antibiotics was 68 minutes, compared with 96 minutes when the order set was not used.

Secondary outcome measures included times to physician assessment, blood draw, and antibiotic order placement. All measures except time to physician assessment were significantly shorter for the FN pathway group than for the comparison cohorts (P less than .001 for all).

Since so many changes were made at once, Dr. Keng and his coauthors noted, “it is difficult to determine the impact of any one change.” Some institutions may have difficulty implementing all the interventions, but immediate triage, automated antibiotic ordering, and EHR use were the changes that had the most impact, he wrote.

“Instituting these changes took less than half a year, and the benefits have persisted for years afterward,” Dr. Sekeres said in an interview.

No study authors reported conflicts of interest.

[email protected]

SEATTLE – It’s time to consider an alternative strategy for evaluating new biomarkers that focuses on the predictive information they add, Michael W. Kattan, Ph.D., said at a joint meeting by Global Biomarkers Consortium and World Cutaneous Malignancies Congress.

“In my view, we get too fixated on P values or hazard ratios and odds ratios. Instead, we need to step back and think more about what the goal of any new marker is, and often, it’s to improve our ability to predict a patient outcome,” said Dr. Kattan, professor of medicine, epidemiology, and biostatistics at Case Western Reserve University, Cleveland, and chair of quantitative health sciences at the Cleveland Clinic. “If that’s the case, why not worry more about something like incremental predictive accuracy or incremental predictive ability associated with that new marker, and make our decisions and our modeling steps toward that?”

The long-used, conventional three-step approach to evaluating a new biomarker – assessing its correlation with an established biomarker, its association with an outcome in univariate analysis, and finally its performance in a multivariate analysis (J Natl Cancer Inst. 2003;95:634-5) – has considerable issues, according to Dr. Kattan.

In particular, the multivariate analysis is problematic. “My P value is testing whether my hazard ratio is 1, it’s not per se an improvement in predictive accuracy, which is what I’m going to argue that the new marker should do,” he said. But more concerning is the fact that the hazard ratio is affected by factors the investigators control, such as whether the new biomarker is coded as a continuous or categorical variable, which established biomarkers are included, and any data transformations done.

“At the end of the day, things are getting a little bit subjective because I have a bunch of knobs under my control as the keeper of the data. I can turn all of these knobs, and unfortunately, I don’t have excellent arguments to defend how I would do that, and they may very well affect the [hazard ratio] that has everyone’s attention,” Dr. Kattan elaborated.

Thus, an alternative approach is needed, one that tests the new biomarker as part of a model and addresses the central question of whether it improves predictive accuracy, he maintained. “It’s [comparing] a model of markers that lacks the new marker versus a model of markers that contains the new marker. So it’s a model versus model comparison, it’s not simply looking at the marker in isolation, which is where we get in trouble with the typical way.”

Furthermore, aiming for the most accurate model removes much of the subjectivity of the conventional approach, he added. “Remember, I said there were knobs I could turn that might change the hazard ratio and I didn’t have a good defense for how I would turn these knobs. … Now I do, now I have an explicit goal: I want to have a prediction model that predicts patient outcome as accurately as I can. So whatever I’m doing with my knobs and stuff, that ought to be delivering a more accurate prediction model.”

Dr. Kattan outlined a four-step alternative approach to evaluating new biomarkers. The first step entails calculating the improvement in the concordance index, similar to an area under the receiver operating characteristic (ROC) curve, with the new biomarker. Ideally, that number will increase in a model that contains the marker, indicating an improvement in predictive accuracy.

In the second step, which assesses model calibration, established and new biomarkers are entered into a multivariate model predicting the outcome of interest (Clin Cancer Res. 2004;10:822-4). If the concordance index drops by a clinically significant degree when the new biomarker is omitted, indicating a loss of predictive accuracy, it advances.

The third step is to construct scatterplots comparing results obtained with prediction models of the outcome, say, 10-year progression-free survival, that do and do not contain the new marker, say, surgeon experience with prostatectomy (Cancer. 2009;115:1005-10). If the improvement in accuracy here is clinically significant, the marker again advances.

In the fourth and final step, decision curve analysis, the net benefit is plotted as a function of the threshold for clinical action (Epidemiology. 2010;21:128-38). “This gets at, should I be making clinical decisions based on the prediction model, or should I just treat everyone or treat no one. It’s a way of looking at what the net benefit is of the prediction model across the spectrum of predictions,” Dr. Kattan explained. “So you would first decide what’s my threshold for action … where’s it going to change what I do, and then read upwards [in the plot] and see what the net benefit is.”

Dr. Kattan disclosed that he receives consulting fees from Bayer, Exosome, GlaxoSmithKline, HistoSonics, and Merck.

SEATTLE – It’s time to consider an alternative strategy for evaluating new biomarkers that focuses on the predictive information they add, Michael W. Kattan, Ph.D., said at a joint meeting by Global Biomarkers Consortium and World Cutaneous Malignancies Congress.

“In my view, we get too fixated on P values or hazard ratios and odds ratios. Instead, we need to step back and think more about what the goal of any new marker is, and often, it’s to improve our ability to predict a patient outcome,” said Dr. Kattan, professor of medicine, epidemiology, and biostatistics at Case Western Reserve University, Cleveland, and chair of quantitative health sciences at the Cleveland Clinic. “If that’s the case, why not worry more about something like incremental predictive accuracy or incremental predictive ability associated with that new marker, and make our decisions and our modeling steps toward that?”

The long-used, conventional three-step approach to evaluating a new biomarker – assessing its correlation with an established biomarker, its association with an outcome in univariate analysis, and finally its performance in a multivariate analysis (J Natl Cancer Inst. 2003;95:634-5) – has considerable issues, according to Dr. Kattan.

In particular, the multivariate analysis is problematic. “My P value is testing whether my hazard ratio is 1, it’s not per se an improvement in predictive accuracy, which is what I’m going to argue that the new marker should do,” he said. But more concerning is the fact that the hazard ratio is affected by factors the investigators control, such as whether the new biomarker is coded as a continuous or categorical variable, which established biomarkers are included, and any data transformations done.

“At the end of the day, things are getting a little bit subjective because I have a bunch of knobs under my control as the keeper of the data. I can turn all of these knobs, and unfortunately, I don’t have excellent arguments to defend how I would do that, and they may very well affect the [hazard ratio] that has everyone’s attention,” Dr. Kattan elaborated.

Thus, an alternative approach is needed, one that tests the new biomarker as part of a model and addresses the central question of whether it improves predictive accuracy, he maintained. “It’s [comparing] a model of markers that lacks the new marker versus a model of markers that contains the new marker. So it’s a model versus model comparison, it’s not simply looking at the marker in isolation, which is where we get in trouble with the typical way.”

Furthermore, aiming for the most accurate model removes much of the subjectivity of the conventional approach, he added. “Remember, I said there were knobs I could turn that might change the hazard ratio and I didn’t have a good defense for how I would turn these knobs. … Now I do, now I have an explicit goal: I want to have a prediction model that predicts patient outcome as accurately as I can. So whatever I’m doing with my knobs and stuff, that ought to be delivering a more accurate prediction model.”

Dr. Kattan outlined a four-step alternative approach to evaluating new biomarkers. The first step entails calculating the improvement in the concordance index, similar to an area under the receiver operating characteristic (ROC) curve, with the new biomarker. Ideally, that number will increase in a model that contains the marker, indicating an improvement in predictive accuracy.

In the second step, which assesses model calibration, established and new biomarkers are entered into a multivariate model predicting the outcome of interest (Clin Cancer Res. 2004;10:822-4). If the concordance index drops by a clinically significant degree when the new biomarker is omitted, indicating a loss of predictive accuracy, it advances.

The third step is to construct scatterplots comparing results obtained with prediction models of the outcome, say, 10-year progression-free survival, that do and do not contain the new marker, say, surgeon experience with prostatectomy (Cancer. 2009;115:1005-10). If the improvement in accuracy here is clinically significant, the marker again advances.

In the fourth and final step, decision curve analysis, the net benefit is plotted as a function of the threshold for clinical action (Epidemiology. 2010;21:128-38). “This gets at, should I be making clinical decisions based on the prediction model, or should I just treat everyone or treat no one. It’s a way of looking at what the net benefit is of the prediction model across the spectrum of predictions,” Dr. Kattan explained. “So you would first decide what’s my threshold for action … where’s it going to change what I do, and then read upwards [in the plot] and see what the net benefit is.”

Dr. Kattan disclosed that he receives consulting fees from Bayer, Exosome, GlaxoSmithKline, HistoSonics, and Merck.

SEATTLE – It’s time to consider an alternative strategy for evaluating new biomarkers that focuses on the predictive information they add, Michael W. Kattan, Ph.D., said at a joint meeting by Global Biomarkers Consortium and World Cutaneous Malignancies Congress.

“In my view, we get too fixated on P values or hazard ratios and odds ratios. Instead, we need to step back and think more about what the goal of any new marker is, and often, it’s to improve our ability to predict a patient outcome,” said Dr. Kattan, professor of medicine, epidemiology, and biostatistics at Case Western Reserve University, Cleveland, and chair of quantitative health sciences at the Cleveland Clinic. “If that’s the case, why not worry more about something like incremental predictive accuracy or incremental predictive ability associated with that new marker, and make our decisions and our modeling steps toward that?”

The long-used, conventional three-step approach to evaluating a new biomarker – assessing its correlation with an established biomarker, its association with an outcome in univariate analysis, and finally its performance in a multivariate analysis (J Natl Cancer Inst. 2003;95:634-5) – has considerable issues, according to Dr. Kattan.

In particular, the multivariate analysis is problematic. “My P value is testing whether my hazard ratio is 1, it’s not per se an improvement in predictive accuracy, which is what I’m going to argue that the new marker should do,” he said. But more concerning is the fact that the hazard ratio is affected by factors the investigators control, such as whether the new biomarker is coded as a continuous or categorical variable, which established biomarkers are included, and any data transformations done.

“At the end of the day, things are getting a little bit subjective because I have a bunch of knobs under my control as the keeper of the data. I can turn all of these knobs, and unfortunately, I don’t have excellent arguments to defend how I would do that, and they may very well affect the [hazard ratio] that has everyone’s attention,” Dr. Kattan elaborated.

Thus, an alternative approach is needed, one that tests the new biomarker as part of a model and addresses the central question of whether it improves predictive accuracy, he maintained. “It’s [comparing] a model of markers that lacks the new marker versus a model of markers that contains the new marker. So it’s a model versus model comparison, it’s not simply looking at the marker in isolation, which is where we get in trouble with the typical way.”

Furthermore, aiming for the most accurate model removes much of the subjectivity of the conventional approach, he added. “Remember, I said there were knobs I could turn that might change the hazard ratio and I didn’t have a good defense for how I would turn these knobs. … Now I do, now I have an explicit goal: I want to have a prediction model that predicts patient outcome as accurately as I can. So whatever I’m doing with my knobs and stuff, that ought to be delivering a more accurate prediction model.”

Dr. Kattan outlined a four-step alternative approach to evaluating new biomarkers. The first step entails calculating the improvement in the concordance index, similar to an area under the receiver operating characteristic (ROC) curve, with the new biomarker. Ideally, that number will increase in a model that contains the marker, indicating an improvement in predictive accuracy.

In the second step, which assesses model calibration, established and new biomarkers are entered into a multivariate model predicting the outcome of interest (Clin Cancer Res. 2004;10:822-4). If the concordance index drops by a clinically significant degree when the new biomarker is omitted, indicating a loss of predictive accuracy, it advances.

The third step is to construct scatterplots comparing results obtained with prediction models of the outcome, say, 10-year progression-free survival, that do and do not contain the new marker, say, surgeon experience with prostatectomy (Cancer. 2009;115:1005-10). If the improvement in accuracy here is clinically significant, the marker again advances.

In the fourth and final step, decision curve analysis, the net benefit is plotted as a function of the threshold for clinical action (Epidemiology. 2010;21:128-38). “This gets at, should I be making clinical decisions based on the prediction model, or should I just treat everyone or treat no one. It’s a way of looking at what the net benefit is of the prediction model across the spectrum of predictions,” Dr. Kattan explained. “So you would first decide what’s my threshold for action … where’s it going to change what I do, and then read upwards [in the plot] and see what the net benefit is.”

Dr. Kattan disclosed that he receives consulting fees from Bayer, Exosome, GlaxoSmithKline, HistoSonics, and Merck.