ORLANDO – An endoscopic approach to treatment of acute necrotizing pancreatitis was substantially safer than was minimally invasive surgical treatment in a randomized study of 66 patients.

Performing drainage and necrosectomy endoscopically in 34 patients with necrotizing pancreatitis that was symptomatic, infected, or both resulted in a 12% rate of major adverse events over the 3 months following intervention compared with a 38% rate among 32 similar patients who underwent laparoscopic drainage followed by either internal debridement or video-assisted retroperitoneal debridement, Ji Young Bang, MD, said at the World Congress of Gastroenterology at ACG 2017.

This statistically significant reduction in the study’s primary endpoint was driven primarily by a major reduction in the incidence of pancreaticocutaneous fistula, which occurred in none of the endoscopy patients and in eight (25%) of the surgery patients, and a smaller reduction in enterocutaneous fistula, which occurred in none of the endoscopy patients and in four (13%) of the patients treated surgically, said Dr. Bang, a gastroenterologist at the Center for Interventional Endoscopy at Florida Hospital, Orlando.

Based on these results, the endoscopic approach “is the treatment of the future,” Dr. Bang said in a video interview. Although the randomized study had a modest number of patients, it was adequately powered to address the hypothesis that endoscopy caused fewer major adverse events than did minimally invasive surgery, and hence the findings should have “an important clinical impact” on the choice of endoscopy or a minimally invasive surgical approach. But Dr. Bang also stressed that a successful endoscopic approach as obtained in this study requires treatment at a center that can offer multidisciplinary expertise from gastrointestinal endoscopists, surgeons, and radiologists, as well as infectious disease physicians, to minimize infections.

Prior to this study, results from the Pancreatitis, Endoscopic Transgastric vs Primary Necrosectomy in Patients With Infected Necrosis (PENGUIN) study run in the Netherlands had also shown significantly fewer adverse events with endoscopic treatment compared with laparoscopic surgery in 20 randomized patients (JAMA. 2012 Mar 14;307[10]:1053-61).

The study reported by Dr. Bang, the Minimally Invasive Surgery vs. Endoscopy Randomized (MISER) trial, enrolled patients with an average necrotic collection size of about 11 cm. The average age of the patients was 59 years. Nearly half of the patients had confirmed infected necrosis. More than 90% had American Society of Anesthesiologists class III or IV disease, and about half had systemic inflammatory response syndrome. All patients had disease that was amenable to both the endoscopic and minimally invasive surgical approaches.

The study’s primary endpoint included several other adverse events in addition to fistulas during 3-month follow-up: death, new-onset organ failure or multiple systemic dysfunction, visceral perforation, and intra-abdominal bleeding. The incidence of each of these outcomes was about the same in the two study arms.

The results also showed that endoscopy was significantly better than surgery for several other secondary outcomes, including new-onset systemic inflammatory response syndrome as well as the prevalence of this complication 3 days after intervention (21% compared with 66%), days in the ICU, average total procedure and hospitalization cost ($76,000 compared with $117,000), and physical quality of life 3 months after treatment. For all other measured outcomes the endoscopic approach and surgical approach produced similar outcomes, and no outcome measured showed that endoscopy was significantly inferior to surgery, Dr. Bang reported.

[email protected]

On Twitter @mitchelzoler

ORLANDO – An endoscopic approach to treatment of acute necrotizing pancreatitis was substantially safer than was minimally invasive surgical treatment in a randomized study of 66 patients.

Performing drainage and necrosectomy endoscopically in 34 patients with necrotizing pancreatitis that was symptomatic, infected, or both resulted in a 12% rate of major adverse events over the 3 months following intervention compared with a 38% rate among 32 similar patients who underwent laparoscopic drainage followed by either internal debridement or video-assisted retroperitoneal debridement, Ji Young Bang, MD, said at the World Congress of Gastroenterology at ACG 2017.

This statistically significant reduction in the study’s primary endpoint was driven primarily by a major reduction in the incidence of pancreaticocutaneous fistula, which occurred in none of the endoscopy patients and in eight (25%) of the surgery patients, and a smaller reduction in enterocutaneous fistula, which occurred in none of the endoscopy patients and in four (13%) of the patients treated surgically, said Dr. Bang, a gastroenterologist at the Center for Interventional Endoscopy at Florida Hospital, Orlando.

Based on these results, the endoscopic approach “is the treatment of the future,” Dr. Bang said in a video interview. Although the randomized study had a modest number of patients, it was adequately powered to address the hypothesis that endoscopy caused fewer major adverse events than did minimally invasive surgery, and hence the findings should have “an important clinical impact” on the choice of endoscopy or a minimally invasive surgical approach. But Dr. Bang also stressed that a successful endoscopic approach as obtained in this study requires treatment at a center that can offer multidisciplinary expertise from gastrointestinal endoscopists, surgeons, and radiologists, as well as infectious disease physicians, to minimize infections.

Prior to this study, results from the Pancreatitis, Endoscopic Transgastric vs Primary Necrosectomy in Patients With Infected Necrosis (PENGUIN) study run in the Netherlands had also shown significantly fewer adverse events with endoscopic treatment compared with laparoscopic surgery in 20 randomized patients (JAMA. 2012 Mar 14;307[10]:1053-61).

The study reported by Dr. Bang, the Minimally Invasive Surgery vs. Endoscopy Randomized (MISER) trial, enrolled patients with an average necrotic collection size of about 11 cm. The average age of the patients was 59 years. Nearly half of the patients had confirmed infected necrosis. More than 90% had American Society of Anesthesiologists class III or IV disease, and about half had systemic inflammatory response syndrome. All patients had disease that was amenable to both the endoscopic and minimally invasive surgical approaches.

The study’s primary endpoint included several other adverse events in addition to fistulas during 3-month follow-up: death, new-onset organ failure or multiple systemic dysfunction, visceral perforation, and intra-abdominal bleeding. The incidence of each of these outcomes was about the same in the two study arms.

The results also showed that endoscopy was significantly better than surgery for several other secondary outcomes, including new-onset systemic inflammatory response syndrome as well as the prevalence of this complication 3 days after intervention (21% compared with 66%), days in the ICU, average total procedure and hospitalization cost ($76,000 compared with $117,000), and physical quality of life 3 months after treatment. For all other measured outcomes the endoscopic approach and surgical approach produced similar outcomes, and no outcome measured showed that endoscopy was significantly inferior to surgery, Dr. Bang reported.

[email protected]

On Twitter @mitchelzoler

ORLANDO – An endoscopic approach to treatment of acute necrotizing pancreatitis was substantially safer than was minimally invasive surgical treatment in a randomized study of 66 patients.

Performing drainage and necrosectomy endoscopically in 34 patients with necrotizing pancreatitis that was symptomatic, infected, or both resulted in a 12% rate of major adverse events over the 3 months following intervention compared with a 38% rate among 32 similar patients who underwent laparoscopic drainage followed by either internal debridement or video-assisted retroperitoneal debridement, Ji Young Bang, MD, said at the World Congress of Gastroenterology at ACG 2017.

This statistically significant reduction in the study’s primary endpoint was driven primarily by a major reduction in the incidence of pancreaticocutaneous fistula, which occurred in none of the endoscopy patients and in eight (25%) of the surgery patients, and a smaller reduction in enterocutaneous fistula, which occurred in none of the endoscopy patients and in four (13%) of the patients treated surgically, said Dr. Bang, a gastroenterologist at the Center for Interventional Endoscopy at Florida Hospital, Orlando.

Based on these results, the endoscopic approach “is the treatment of the future,” Dr. Bang said in a video interview. Although the randomized study had a modest number of patients, it was adequately powered to address the hypothesis that endoscopy caused fewer major adverse events than did minimally invasive surgery, and hence the findings should have “an important clinical impact” on the choice of endoscopy or a minimally invasive surgical approach. But Dr. Bang also stressed that a successful endoscopic approach as obtained in this study requires treatment at a center that can offer multidisciplinary expertise from gastrointestinal endoscopists, surgeons, and radiologists, as well as infectious disease physicians, to minimize infections.

Prior to this study, results from the Pancreatitis, Endoscopic Transgastric vs Primary Necrosectomy in Patients With Infected Necrosis (PENGUIN) study run in the Netherlands had also shown significantly fewer adverse events with endoscopic treatment compared with laparoscopic surgery in 20 randomized patients (JAMA. 2012 Mar 14;307[10]:1053-61).

The study reported by Dr. Bang, the Minimally Invasive Surgery vs. Endoscopy Randomized (MISER) trial, enrolled patients with an average necrotic collection size of about 11 cm. The average age of the patients was 59 years. Nearly half of the patients had confirmed infected necrosis. More than 90% had American Society of Anesthesiologists class III or IV disease, and about half had systemic inflammatory response syndrome. All patients had disease that was amenable to both the endoscopic and minimally invasive surgical approaches.

The study’s primary endpoint included several other adverse events in addition to fistulas during 3-month follow-up: death, new-onset organ failure or multiple systemic dysfunction, visceral perforation, and intra-abdominal bleeding. The incidence of each of these outcomes was about the same in the two study arms.

The results also showed that endoscopy was significantly better than surgery for several other secondary outcomes, including new-onset systemic inflammatory response syndrome as well as the prevalence of this complication 3 days after intervention (21% compared with 66%), days in the ICU, average total procedure and hospitalization cost ($76,000 compared with $117,000), and physical quality of life 3 months after treatment. For all other measured outcomes the endoscopic approach and surgical approach produced similar outcomes, and no outcome measured showed that endoscopy was significantly inferior to surgery, Dr. Bang reported.

[email protected]

On Twitter @mitchelzoler

LISBON – Exercise was associated with a lower risk of all-cause mortality in patients with type 1 diabetes mellitus, regardless of whether or not they also had chronic kidney disease, according to an analysis of data from a large ongoing population study.

Fully adjusted hazard ratios comparing low versus moderate-to-high amounts of physical activity, intensity, frequency, and duration were a respective 1.63, 2.17, 2.07, and 1.86 in patients without CKD.

The corresponding HRs in patients with comorbid CKD were 1.47, 1.39, 1.90, and 1.49, although only the total exercise amount and frequency were statistically significant in this study group.

[email protected]

LISBON – Exercise was associated with a lower risk of all-cause mortality in patients with type 1 diabetes mellitus, regardless of whether or not they also had chronic kidney disease, according to an analysis of data from a large ongoing population study.

Fully adjusted hazard ratios comparing low versus moderate-to-high amounts of physical activity, intensity, frequency, and duration were a respective 1.63, 2.17, 2.07, and 1.86 in patients without CKD.

The corresponding HRs in patients with comorbid CKD were 1.47, 1.39, 1.90, and 1.49, although only the total exercise amount and frequency were statistically significant in this study group.

[email protected]

LISBON – Exercise was associated with a lower risk of all-cause mortality in patients with type 1 diabetes mellitus, regardless of whether or not they also had chronic kidney disease, according to an analysis of data from a large ongoing population study.

Fully adjusted hazard ratios comparing low versus moderate-to-high amounts of physical activity, intensity, frequency, and duration were a respective 1.63, 2.17, 2.07, and 1.86 in patients without CKD.

The corresponding HRs in patients with comorbid CKD were 1.47, 1.39, 1.90, and 1.49, although only the total exercise amount and frequency were statistically significant in this study group.

[email protected]

DALLAS – Patients newly diagnosed with heart failure with reduced ejection fraction had about an 8% incidence of MIs during the subsequent 9 months, and a 5% incidence of ischemic strokes in a retrospective review of more than 1,600 community-dwelling U.S. patients.

The MI and ischemic stroke incidence rates in heart failure patients with reduced ejection fraction (HFrEF) were both significantly higher than in more than 4,000 patients with heart failure with preserved ejection fraction (HFpEF), Gregg C. Fonarow, MD, said while presenting a poster at the annual scientific meeting of the Heart Failure Society of America.

The findings suggest that greater attention is needed to reduce the risks for MI and stroke in HFrEF patients, suggested Dr. Fonarow, professor and cochief of cardiology at the University of California, Los Angeles, and his associates in their poster.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

DALLAS – Patients newly diagnosed with heart failure with reduced ejection fraction had about an 8% incidence of MIs during the subsequent 9 months, and a 5% incidence of ischemic strokes in a retrospective review of more than 1,600 community-dwelling U.S. patients.

The MI and ischemic stroke incidence rates in heart failure patients with reduced ejection fraction (HFrEF) were both significantly higher than in more than 4,000 patients with heart failure with preserved ejection fraction (HFpEF), Gregg C. Fonarow, MD, said while presenting a poster at the annual scientific meeting of the Heart Failure Society of America.

The findings suggest that greater attention is needed to reduce the risks for MI and stroke in HFrEF patients, suggested Dr. Fonarow, professor and cochief of cardiology at the University of California, Los Angeles, and his associates in their poster.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

DALLAS – Patients newly diagnosed with heart failure with reduced ejection fraction had about an 8% incidence of MIs during the subsequent 9 months, and a 5% incidence of ischemic strokes in a retrospective review of more than 1,600 community-dwelling U.S. patients.

The MI and ischemic stroke incidence rates in heart failure patients with reduced ejection fraction (HFrEF) were both significantly higher than in more than 4,000 patients with heart failure with preserved ejection fraction (HFpEF), Gregg C. Fonarow, MD, said while presenting a poster at the annual scientific meeting of the Heart Failure Society of America.

The findings suggest that greater attention is needed to reduce the risks for MI and stroke in HFrEF patients, suggested Dr. Fonarow, professor and cochief of cardiology at the University of California, Los Angeles, and his associates in their poster.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

MADRID – Although pembrolizumab (Keytruda) was associated with a 19% reduction in the risk of death compared with the standard of care in patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE 040 trial, the immune checkpoint inhibitor just missed meeting its primary efficacy endpoint of an improvement in overall survival.

The fault may lie in the confounding of overall survival results when patients who were initially assigned to standard of care were crossed over to subsequent therapy with a checkpoint inhibitor after the study ended, said lead investigator Ezra Cohen, MD, of Moores Cancer Center at UC San Diego Health Sciences in La Jolla, Calif.

“This was a trial that clearly did not meet its primary endpoint, but was felt to confer some benefit – at least in the opinion of this investigator – to pembrolizumab vs. standard of care,” he said at the European Society for Medical Oncology Congress.

Some math required

Dr. Cohen explained that the statistical design of the trial involved a multiplicity strategy using a family-wise alpha strictly controlled at 0.025. The alpha was allocated in a stepwise fashion. The study hypothesis was that pembrolizumab would have an overall survival (OS) advantage with a one-side alpha, and if that was met, OS would then be looked at in specific cohorts according to expression of the PD ligand 1 (PD-L1) on cells, followed by evaluation of objective response rates and progression-free survival in each subgroup.

The final analysis was to be performed after 380 OS events had occurred among 495 randomized patients. The prespecified efficacy boundary for OS in the intention-to-treat (ITT) population was .0175, translating into a hazard ratio (HR) of 0.80.

Median OS in the ITT population was 8.4 months for the pembrolizumab arm, compared with 7.1 months for the standard-of-care arm. This translated into an HR of 0.81 (P = .0204), which do not reach the aforementioned efficacy boundary.

Rates of 1-year overall survival were 37% in the experimental arm, vs. 27% in the standard-of-care arm.

“When one looks at the biomarker-specific cohorts, we can see that these differences are further exaggerated in favor of pembrolizumab, Dr. Cohen said.

An analysis stratified by patients with PD-L1 expression on 1% or more of cells vs. less than 1% showed median overall OS of 8.7 months for those with higher levels of expression, vs. 7.1 months for expression levels below 1% (HR 0.75, P = .0078).

Similarly, an analysis comparing patients with a tumor proportion score (TPS; expression of PD-L1 in the membranes of 50% or more of tumor cells) with patients whose tumors had lower TPS levels showed a median OS of 11.6 months with pembrolizumab, vs. 7.9 months with standard of care (HR 0.54, P = .0017).

Objective response rates were also significantly higher with pembrolizumab in the patients with higher levels of both overall PD-L1 expression (17.3% vs. 9.9% with standard care), and in patients with 50% or more of tumor cells expressing membrane PD-L1 (26.6% vs. 65%, P = .0009).

In an exploratory analysis, the investigators also found that among patients in the standard of care arm who went on to receive a checkpoint inhibitor as subsequent therapy, the median OS was 20.1 months, compared with 9.8 months for patients who received other subsequent therapies, and 4.8 months for those who did not receive subsequent therapy, suggesting that crossover to a checkpoint inhibitor may have diluted overall survival differences between the trial arms, Dr. Cohen said.

Treatment-related adverse events of any grade were more frequent in the standard of care arm, except for hypothyroidism, which was substantially more frequent with pembrolizumab. The incidence of immune-mediated adverse events other than hypothyroidism was generally similar between the treatment arms.

“I think pembrolizumab, despite not meeting the primary endpoint of overall survival, showed evidence of activity and a [good] safety profile. So I think this study is borderline possible, since there is a 19% reduction in the risk of death, with a hazard ratio borderline to the statistical hypothesis that was initially planned,” said invited discussant Sandrine Faivre, MD, PhD, of Bichat-Beaujon University Hospitals in Paris.

MADRID – Although pembrolizumab (Keytruda) was associated with a 19% reduction in the risk of death compared with the standard of care in patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE 040 trial, the immune checkpoint inhibitor just missed meeting its primary efficacy endpoint of an improvement in overall survival.

The fault may lie in the confounding of overall survival results when patients who were initially assigned to standard of care were crossed over to subsequent therapy with a checkpoint inhibitor after the study ended, said lead investigator Ezra Cohen, MD, of Moores Cancer Center at UC San Diego Health Sciences in La Jolla, Calif.

“This was a trial that clearly did not meet its primary endpoint, but was felt to confer some benefit – at least in the opinion of this investigator – to pembrolizumab vs. standard of care,” he said at the European Society for Medical Oncology Congress.

Some math required

Dr. Cohen explained that the statistical design of the trial involved a multiplicity strategy using a family-wise alpha strictly controlled at 0.025. The alpha was allocated in a stepwise fashion. The study hypothesis was that pembrolizumab would have an overall survival (OS) advantage with a one-side alpha, and if that was met, OS would then be looked at in specific cohorts according to expression of the PD ligand 1 (PD-L1) on cells, followed by evaluation of objective response rates and progression-free survival in each subgroup.

The final analysis was to be performed after 380 OS events had occurred among 495 randomized patients. The prespecified efficacy boundary for OS in the intention-to-treat (ITT) population was .0175, translating into a hazard ratio (HR) of 0.80.

Median OS in the ITT population was 8.4 months for the pembrolizumab arm, compared with 7.1 months for the standard-of-care arm. This translated into an HR of 0.81 (P = .0204), which do not reach the aforementioned efficacy boundary.

Rates of 1-year overall survival were 37% in the experimental arm, vs. 27% in the standard-of-care arm.

“When one looks at the biomarker-specific cohorts, we can see that these differences are further exaggerated in favor of pembrolizumab, Dr. Cohen said.

An analysis stratified by patients with PD-L1 expression on 1% or more of cells vs. less than 1% showed median overall OS of 8.7 months for those with higher levels of expression, vs. 7.1 months for expression levels below 1% (HR 0.75, P = .0078).

Similarly, an analysis comparing patients with a tumor proportion score (TPS; expression of PD-L1 in the membranes of 50% or more of tumor cells) with patients whose tumors had lower TPS levels showed a median OS of 11.6 months with pembrolizumab, vs. 7.9 months with standard of care (HR 0.54, P = .0017).

Objective response rates were also significantly higher with pembrolizumab in the patients with higher levels of both overall PD-L1 expression (17.3% vs. 9.9% with standard care), and in patients with 50% or more of tumor cells expressing membrane PD-L1 (26.6% vs. 65%, P = .0009).

In an exploratory analysis, the investigators also found that among patients in the standard of care arm who went on to receive a checkpoint inhibitor as subsequent therapy, the median OS was 20.1 months, compared with 9.8 months for patients who received other subsequent therapies, and 4.8 months for those who did not receive subsequent therapy, suggesting that crossover to a checkpoint inhibitor may have diluted overall survival differences between the trial arms, Dr. Cohen said.

Treatment-related adverse events of any grade were more frequent in the standard of care arm, except for hypothyroidism, which was substantially more frequent with pembrolizumab. The incidence of immune-mediated adverse events other than hypothyroidism was generally similar between the treatment arms.

“I think pembrolizumab, despite not meeting the primary endpoint of overall survival, showed evidence of activity and a [good] safety profile. So I think this study is borderline possible, since there is a 19% reduction in the risk of death, with a hazard ratio borderline to the statistical hypothesis that was initially planned,” said invited discussant Sandrine Faivre, MD, PhD, of Bichat-Beaujon University Hospitals in Paris.

MADRID – Although pembrolizumab (Keytruda) was associated with a 19% reduction in the risk of death compared with the standard of care in patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE 040 trial, the immune checkpoint inhibitor just missed meeting its primary efficacy endpoint of an improvement in overall survival.

The fault may lie in the confounding of overall survival results when patients who were initially assigned to standard of care were crossed over to subsequent therapy with a checkpoint inhibitor after the study ended, said lead investigator Ezra Cohen, MD, of Moores Cancer Center at UC San Diego Health Sciences in La Jolla, Calif.

“This was a trial that clearly did not meet its primary endpoint, but was felt to confer some benefit – at least in the opinion of this investigator – to pembrolizumab vs. standard of care,” he said at the European Society for Medical Oncology Congress.

Some math required

Dr. Cohen explained that the statistical design of the trial involved a multiplicity strategy using a family-wise alpha strictly controlled at 0.025. The alpha was allocated in a stepwise fashion. The study hypothesis was that pembrolizumab would have an overall survival (OS) advantage with a one-side alpha, and if that was met, OS would then be looked at in specific cohorts according to expression of the PD ligand 1 (PD-L1) on cells, followed by evaluation of objective response rates and progression-free survival in each subgroup.

The final analysis was to be performed after 380 OS events had occurred among 495 randomized patients. The prespecified efficacy boundary for OS in the intention-to-treat (ITT) population was .0175, translating into a hazard ratio (HR) of 0.80.

Median OS in the ITT population was 8.4 months for the pembrolizumab arm, compared with 7.1 months for the standard-of-care arm. This translated into an HR of 0.81 (P = .0204), which do not reach the aforementioned efficacy boundary.

Rates of 1-year overall survival were 37% in the experimental arm, vs. 27% in the standard-of-care arm.

“When one looks at the biomarker-specific cohorts, we can see that these differences are further exaggerated in favor of pembrolizumab, Dr. Cohen said.

An analysis stratified by patients with PD-L1 expression on 1% or more of cells vs. less than 1% showed median overall OS of 8.7 months for those with higher levels of expression, vs. 7.1 months for expression levels below 1% (HR 0.75, P = .0078).

Similarly, an analysis comparing patients with a tumor proportion score (TPS; expression of PD-L1 in the membranes of 50% or more of tumor cells) with patients whose tumors had lower TPS levels showed a median OS of 11.6 months with pembrolizumab, vs. 7.9 months with standard of care (HR 0.54, P = .0017).

Objective response rates were also significantly higher with pembrolizumab in the patients with higher levels of both overall PD-L1 expression (17.3% vs. 9.9% with standard care), and in patients with 50% or more of tumor cells expressing membrane PD-L1 (26.6% vs. 65%, P = .0009).

In an exploratory analysis, the investigators also found that among patients in the standard of care arm who went on to receive a checkpoint inhibitor as subsequent therapy, the median OS was 20.1 months, compared with 9.8 months for patients who received other subsequent therapies, and 4.8 months for those who did not receive subsequent therapy, suggesting that crossover to a checkpoint inhibitor may have diluted overall survival differences between the trial arms, Dr. Cohen said.

Treatment-related adverse events of any grade were more frequent in the standard of care arm, except for hypothyroidism, which was substantially more frequent with pembrolizumab. The incidence of immune-mediated adverse events other than hypothyroidism was generally similar between the treatment arms.

“I think pembrolizumab, despite not meeting the primary endpoint of overall survival, showed evidence of activity and a [good] safety profile. So I think this study is borderline possible, since there is a 19% reduction in the risk of death, with a hazard ratio borderline to the statistical hypothesis that was initially planned,” said invited discussant Sandrine Faivre, MD, PhD, of Bichat-Beaujon University Hospitals in Paris.

Compliant patients are all alike; every noncompliant patient is obstinate in his or her own way. Because of this, persuading patients to make good choices is rarely easy and never universal.

At Kaiser Permanente, we have begun in earnest providing flu shots. Every department participates (even dermatology) with a goal of vaccinating every eligible patient. Most patients want their shot. When patients decline, it’s game on. A rare few decline for justifiable reasons such as an allergy. Most say “no” for flawed reasons: “I never get the flu,” “The shot always gives me the flu,” and “I don’t believe in vaccines,” are common ones.

jabkitticha/Thinkstock

• The “everyone is doing it” technique. At KP, we’ve put up boards with the iconic goal thermometer showing how many flu shots we need to reach our objective. When patients see we’ve given over 1,000 shots in dermatology in just 2 weeks, this technique helps convince them. Patients prefer to be like others rather than to stand out, particularly when there is uncertainty.
• The “this is who you are technique.” Patients hate to be seen as inconsistent. In fact, we are all more likely to make a choice seen as consistent with who we are rather than change our mind, even if doing so is a better choice. Highlight how they have previously shown good decision making and healthy behaviors and point out how getting vaccinated is consonant with who they are. For example: “Being a vegan, you are clearly someone who takes care of her health. Getting the vaccine is similar to choosing to eat plants. It’s what healthy people like you do.”
• The “well, that’s not like you” technique. Here, you point out how their choice is inconsistent with their previous choices. You might say, “Why would you get the hepatitis A vaccine last week and not the flu shot today?” Like the previous technique, this creates cognitive dissonance. You might soften the approach by saying, “You might have thought this,” or “I’m sure you didn’t realize.”
• The emotional decision approach. Making the risk seem real and imminent can combat future discounting. One example might be: “We have had several people hospitalized and one death from the flu in San Diego already.” Use stories and descriptive language to make the risk salient.
• The use your authority approach. The long coat does matter. A more modern version of the paternalistic physician is referred to as “asymmetric” or “light paternalism,” and we should recognize that it might be used to save a life. One example is: “I advise you to get the flu shot because I care about you, and I’m worried you might end up in the hospital or worse if you don’t get it.” There’s a reason why tobacco companies once used doctors in white coats to sell cigarettes – we can be quite persuasive.

Dr. Benabio is director of health care transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Compliant patients are all alike; every noncompliant patient is obstinate in his or her own way. Because of this, persuading patients to make good choices is rarely easy and never universal.

At Kaiser Permanente, we have begun in earnest providing flu shots. Every department participates (even dermatology) with a goal of vaccinating every eligible patient. Most patients want their shot. When patients decline, it’s game on. A rare few decline for justifiable reasons such as an allergy. Most say “no” for flawed reasons: “I never get the flu,” “The shot always gives me the flu,” and “I don’t believe in vaccines,” are common ones.

jabkitticha/Thinkstock

• The “everyone is doing it” technique. At KP, we’ve put up boards with the iconic goal thermometer showing how many flu shots we need to reach our objective. When patients see we’ve given over 1,000 shots in dermatology in just 2 weeks, this technique helps convince them. Patients prefer to be like others rather than to stand out, particularly when there is uncertainty.
• The “this is who you are technique.” Patients hate to be seen as inconsistent. In fact, we are all more likely to make a choice seen as consistent with who we are rather than change our mind, even if doing so is a better choice. Highlight how they have previously shown good decision making and healthy behaviors and point out how getting vaccinated is consonant with who they are. For example: “Being a vegan, you are clearly someone who takes care of her health. Getting the vaccine is similar to choosing to eat plants. It’s what healthy people like you do.”
• The “well, that’s not like you” technique. Here, you point out how their choice is inconsistent with their previous choices. You might say, “Why would you get the hepatitis A vaccine last week and not the flu shot today?” Like the previous technique, this creates cognitive dissonance. You might soften the approach by saying, “You might have thought this,” or “I’m sure you didn’t realize.”
• The emotional decision approach. Making the risk seem real and imminent can combat future discounting. One example might be: “We have had several people hospitalized and one death from the flu in San Diego already.” Use stories and descriptive language to make the risk salient.
• The use your authority approach. The long coat does matter. A more modern version of the paternalistic physician is referred to as “asymmetric” or “light paternalism,” and we should recognize that it might be used to save a life. One example is: “I advise you to get the flu shot because I care about you, and I’m worried you might end up in the hospital or worse if you don’t get it.” There’s a reason why tobacco companies once used doctors in white coats to sell cigarettes – we can be quite persuasive.

Dr. Benabio is director of health care transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Compliant patients are all alike; every noncompliant patient is obstinate in his or her own way. Because of this, persuading patients to make good choices is rarely easy and never universal.

At Kaiser Permanente, we have begun in earnest providing flu shots. Every department participates (even dermatology) with a goal of vaccinating every eligible patient. Most patients want their shot. When patients decline, it’s game on. A rare few decline for justifiable reasons such as an allergy. Most say “no” for flawed reasons: “I never get the flu,” “The shot always gives me the flu,” and “I don’t believe in vaccines,” are common ones.

jabkitticha/Thinkstock

• The “everyone is doing it” technique. At KP, we’ve put up boards with the iconic goal thermometer showing how many flu shots we need to reach our objective. When patients see we’ve given over 1,000 shots in dermatology in just 2 weeks, this technique helps convince them. Patients prefer to be like others rather than to stand out, particularly when there is uncertainty.
• The “this is who you are technique.” Patients hate to be seen as inconsistent. In fact, we are all more likely to make a choice seen as consistent with who we are rather than change our mind, even if doing so is a better choice. Highlight how they have previously shown good decision making and healthy behaviors and point out how getting vaccinated is consonant with who they are. For example: “Being a vegan, you are clearly someone who takes care of her health. Getting the vaccine is similar to choosing to eat plants. It’s what healthy people like you do.”
• The “well, that’s not like you” technique. Here, you point out how their choice is inconsistent with their previous choices. You might say, “Why would you get the hepatitis A vaccine last week and not the flu shot today?” Like the previous technique, this creates cognitive dissonance. You might soften the approach by saying, “You might have thought this,” or “I’m sure you didn’t realize.”
• The emotional decision approach. Making the risk seem real and imminent can combat future discounting. One example might be: “We have had several people hospitalized and one death from the flu in San Diego already.” Use stories and descriptive language to make the risk salient.
• The use your authority approach. The long coat does matter. A more modern version of the paternalistic physician is referred to as “asymmetric” or “light paternalism,” and we should recognize that it might be used to save a life. One example is: “I advise you to get the flu shot because I care about you, and I’m worried you might end up in the hospital or worse if you don’t get it.” There’s a reason why tobacco companies once used doctors in white coats to sell cigarettes – we can be quite persuasive.

Dr. Benabio is director of health care transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Outrage over the high cost of cancer care has focused on skyrocketing drug prices, including the $475,000 price tag for the country’s first gene therapy, Novartis’ Kymriah (tisagenlecleucel), a leukemia treatment approved in August.

But the total costs of tisagenlecleucel and the 21 similar drugs in development – known as CAR T-cell therapies – will be far higher than many have imagined, reaching $1 million or more per patient, according to leading cancer experts. The next CAR T-cell drug could be approved as soon as November.

Although Kymriah’s price tag has “shattered oncology drug pricing norms,” said Leonard Saltz, MD, chief of gastrointestinal oncology at Memorial Sloan Kettering Cancer Center in New York, “the sticker price is just the starting point.”

These therapies lead to a cascade of costs, propelled by serious side effects that require sophisticated management, Dr. Saltz said. For this class of drugs, Dr, Saltz advised consumers to “think of the $475,000 as parts, not labor.”

Hagop Kantarjian, MD, leukemia specialist and professor at the University of Texas MD Anderson Cancer Center, estimates tisagenlecleucel’s total cost could reach $1.5 million.

CAR T-cell therapy is expensive because of the unique way that it works. Doctors harvest patients’ immune cells, genetically alter them to rev up their ability to fight cancer, then reinfuse them into patients.

Taking the brakes off the immune system, Dr. Kantarjian said, can lead to life-threatening complications that require lengthy hospitalizations and expensive medications, which are prescribed in addition to conventional cancer therapy, rather than in place of it.

Keith D. Eaton, MD, a Seattle oncologist, said he ran up medical bills of $500,000 when he participated in a clinical trial of CAR T cells in 2013, even though all patients in the study received the medication for free. Dr. Eaton, who was diagnosed with acute lymphoblastic leukemia (ALL), spent nearly 2 months in the hospital.

Like Dr. Eaton, nearly half of patients who receive CAR T cells develop cytokine storm. Other serious side effects include strokelike symptoms and coma.

The cytokine storm felt like “the worst flu of your life,” said Dr. Eaton, now aged 51 years. His fever spiked so high that a hospital nurse assumed the thermometer was broken. Dr. Eaton replied, “It’s not broken. My temperature is too high to register on the thermometer.”

Although Dr. Eaton recovered, he wasn’t done with treatment. His doctors recommended a bone marrow transplant, another harrowing procedure, at a cost of hundreds of thousands of dollars.

Dr. Eaton said he feels fortunate to be healthy today, with tests showing no evidence of leukemia. His insurer paid for almost everything.

Kymriah’s sticker price is especially “outrageous” given its relatively low manufacturing costs, said Walid F. Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

The gene therapy process used to create tisagenlecleucel costs about $15,000, according to a 2012 presentation by Carl H. June, MD, who pioneered CAR T-cell research at the University of Pennsylvania in Philadelphia. Dr. June could not be reached for comment.

To quell unrest about price, Novartis has offered patients and insurers a new twist on the money-back guarantee.

Novartis will charge for the drug only if patients go into remission within 1 month of treatment. In a key clinical trial, 83% of the children and young adults treated with tisagenlecleucel went into remission within 3 months. Novartis calls the plan “outcomes-based pricing.”

Novartis is “working through the specific details” of how the pricing plan will affect the Centers for Medicare & Medicaid Services, which pays for care for many cancer patients, company spokesperson Julie Masow said. “There are many hurdles” to this type of pricing plan but, Ms. Masow said, “Novartis is committed to making this happen.”

She also said that Kymriah’s manufacturing costs are much higher than $15,000, although she didn’t cite a specific dollar amount. She noted that Novartis has invested heavily in the technology, designing “an innovative manufacturing facility and process specifically for cellular therapies.”

As for Kymriah-related hospital and medication charges, “costs will vary from patient to patient and treatment center to treatment center, based on the level of care each patient requires,” Ms. Masow said. “Kymriah is a one-time treatment that has shown remarkable early, deep, and durable responses in these children who are very sick and often out of options.”

Some doctors said tisagenlecleucel, which could be used by about 600 patients a year, offers an incalculable benefit for desperately ill young people. The drug is approved for children and young adults with B-cell ALL who already have been treated with at least two other cancer therapies.

“A kid’s life is priceless,” said Michelle Hermiston, MD, director of pediatric immunotherapy at Benioff Children’s Hospital, at the University of California, San Francisco. “Any given kid has the potential to make financial impacts over a lifetime that far outweigh the cost of their cure. From this perspective, every child in my mind deserves the best curative therapy we can offer.”

Other cancer doctors say the Novartis plan is no bargain.

About 36% of patients who go into remission with tisagenlecleucel relapse within 1 year, said Vinay Prasad, MD, of Oregon Health & Science University, Portland. Many of these patients will need additional treatment, said Dr. Prasad, who wrote an editorial about tisagenlecleucel’s price Oct. 4 in Nature.

“If you’ve paid half a million dollars for drugs and half a million dollars for care, and a year later your cancer is back, is that a good deal?” asked Dr. Saltz, who cowrote a recent editorial on tisagenlecleucel’s price in JAMA.

Steve Miller, MD, chief medical officer for Express Scripts, said it would be more fair to judge Kymriah’s success after 6 months of treatment, rather than 1 month. Dr. Prasad goes even further. He said Novartis should issue refunds for any patient who relapses within 3 years.

A consumer-advocate group called Patients for Affordable Drugs also has said that tisagenlecleucel costs too much, given that the federal government spent more than $200 million over 2 decades to support the basic research into CAR T-cell therapy, long before Novartis bought the rights.

Rep. Lloyd Doggett (D-Texas) wrote a letter to the Medicare program’s director last month asking for details on how the Novartis payment deal will work.

“As Big Pharma continues to put price gouging before patient access, companies will point more and more proudly at their pricing agreements,” Rep. Doggett wrote. “But taxpayers deserve to know more about how these agreements will work – whether they will actually save the government money, defray these massive costs, and ensure that they can access lifesaving medications.”
 

KHN’s coverage related to aging & improving care of older adults is supported by The John A. Hartford Foundation. Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Outrage over the high cost of cancer care has focused on skyrocketing drug prices, including the $475,000 price tag for the country’s first gene therapy, Novartis’ Kymriah (tisagenlecleucel), a leukemia treatment approved in August.

But the total costs of tisagenlecleucel and the 21 similar drugs in development – known as CAR T-cell therapies – will be far higher than many have imagined, reaching $1 million or more per patient, according to leading cancer experts. The next CAR T-cell drug could be approved as soon as November.

Although Kymriah’s price tag has “shattered oncology drug pricing norms,” said Leonard Saltz, MD, chief of gastrointestinal oncology at Memorial Sloan Kettering Cancer Center in New York, “the sticker price is just the starting point.”

These therapies lead to a cascade of costs, propelled by serious side effects that require sophisticated management, Dr. Saltz said. For this class of drugs, Dr, Saltz advised consumers to “think of the $475,000 as parts, not labor.”

Hagop Kantarjian, MD, leukemia specialist and professor at the University of Texas MD Anderson Cancer Center, estimates tisagenlecleucel’s total cost could reach $1.5 million.

CAR T-cell therapy is expensive because of the unique way that it works. Doctors harvest patients’ immune cells, genetically alter them to rev up their ability to fight cancer, then reinfuse them into patients.

Taking the brakes off the immune system, Dr. Kantarjian said, can lead to life-threatening complications that require lengthy hospitalizations and expensive medications, which are prescribed in addition to conventional cancer therapy, rather than in place of it.

Keith D. Eaton, MD, a Seattle oncologist, said he ran up medical bills of $500,000 when he participated in a clinical trial of CAR T cells in 2013, even though all patients in the study received the medication for free. Dr. Eaton, who was diagnosed with acute lymphoblastic leukemia (ALL), spent nearly 2 months in the hospital.

Like Dr. Eaton, nearly half of patients who receive CAR T cells develop cytokine storm. Other serious side effects include strokelike symptoms and coma.

The cytokine storm felt like “the worst flu of your life,” said Dr. Eaton, now aged 51 years. His fever spiked so high that a hospital nurse assumed the thermometer was broken. Dr. Eaton replied, “It’s not broken. My temperature is too high to register on the thermometer.”

Although Dr. Eaton recovered, he wasn’t done with treatment. His doctors recommended a bone marrow transplant, another harrowing procedure, at a cost of hundreds of thousands of dollars.

Dr. Eaton said he feels fortunate to be healthy today, with tests showing no evidence of leukemia. His insurer paid for almost everything.

Kymriah’s sticker price is especially “outrageous” given its relatively low manufacturing costs, said Walid F. Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

The gene therapy process used to create tisagenlecleucel costs about $15,000, according to a 2012 presentation by Carl H. June, MD, who pioneered CAR T-cell research at the University of Pennsylvania in Philadelphia. Dr. June could not be reached for comment.

To quell unrest about price, Novartis has offered patients and insurers a new twist on the money-back guarantee.

Novartis will charge for the drug only if patients go into remission within 1 month of treatment. In a key clinical trial, 83% of the children and young adults treated with tisagenlecleucel went into remission within 3 months. Novartis calls the plan “outcomes-based pricing.”

Novartis is “working through the specific details” of how the pricing plan will affect the Centers for Medicare & Medicaid Services, which pays for care for many cancer patients, company spokesperson Julie Masow said. “There are many hurdles” to this type of pricing plan but, Ms. Masow said, “Novartis is committed to making this happen.”

She also said that Kymriah’s manufacturing costs are much higher than $15,000, although she didn’t cite a specific dollar amount. She noted that Novartis has invested heavily in the technology, designing “an innovative manufacturing facility and process specifically for cellular therapies.”

As for Kymriah-related hospital and medication charges, “costs will vary from patient to patient and treatment center to treatment center, based on the level of care each patient requires,” Ms. Masow said. “Kymriah is a one-time treatment that has shown remarkable early, deep, and durable responses in these children who are very sick and often out of options.”

Some doctors said tisagenlecleucel, which could be used by about 600 patients a year, offers an incalculable benefit for desperately ill young people. The drug is approved for children and young adults with B-cell ALL who already have been treated with at least two other cancer therapies.

“A kid’s life is priceless,” said Michelle Hermiston, MD, director of pediatric immunotherapy at Benioff Children’s Hospital, at the University of California, San Francisco. “Any given kid has the potential to make financial impacts over a lifetime that far outweigh the cost of their cure. From this perspective, every child in my mind deserves the best curative therapy we can offer.”

Other cancer doctors say the Novartis plan is no bargain.

About 36% of patients who go into remission with tisagenlecleucel relapse within 1 year, said Vinay Prasad, MD, of Oregon Health & Science University, Portland. Many of these patients will need additional treatment, said Dr. Prasad, who wrote an editorial about tisagenlecleucel’s price Oct. 4 in Nature.

“If you’ve paid half a million dollars for drugs and half a million dollars for care, and a year later your cancer is back, is that a good deal?” asked Dr. Saltz, who cowrote a recent editorial on tisagenlecleucel’s price in JAMA.

Steve Miller, MD, chief medical officer for Express Scripts, said it would be more fair to judge Kymriah’s success after 6 months of treatment, rather than 1 month. Dr. Prasad goes even further. He said Novartis should issue refunds for any patient who relapses within 3 years.

A consumer-advocate group called Patients for Affordable Drugs also has said that tisagenlecleucel costs too much, given that the federal government spent more than $200 million over 2 decades to support the basic research into CAR T-cell therapy, long before Novartis bought the rights.

Rep. Lloyd Doggett (D-Texas) wrote a letter to the Medicare program’s director last month asking for details on how the Novartis payment deal will work.

“As Big Pharma continues to put price gouging before patient access, companies will point more and more proudly at their pricing agreements,” Rep. Doggett wrote. “But taxpayers deserve to know more about how these agreements will work – whether they will actually save the government money, defray these massive costs, and ensure that they can access lifesaving medications.”
 

KHN’s coverage related to aging & improving care of older adults is supported by The John A. Hartford Foundation. Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

Outrage over the high cost of cancer care has focused on skyrocketing drug prices, including the $475,000 price tag for the country’s first gene therapy, Novartis’ Kymriah (tisagenlecleucel), a leukemia treatment approved in August.

But the total costs of tisagenlecleucel and the 21 similar drugs in development – known as CAR T-cell therapies – will be far higher than many have imagined, reaching $1 million or more per patient, according to leading cancer experts. The next CAR T-cell drug could be approved as soon as November.

Although Kymriah’s price tag has “shattered oncology drug pricing norms,” said Leonard Saltz, MD, chief of gastrointestinal oncology at Memorial Sloan Kettering Cancer Center in New York, “the sticker price is just the starting point.”

These therapies lead to a cascade of costs, propelled by serious side effects that require sophisticated management, Dr. Saltz said. For this class of drugs, Dr, Saltz advised consumers to “think of the $475,000 as parts, not labor.”

Hagop Kantarjian, MD, leukemia specialist and professor at the University of Texas MD Anderson Cancer Center, estimates tisagenlecleucel’s total cost could reach $1.5 million.

CAR T-cell therapy is expensive because of the unique way that it works. Doctors harvest patients’ immune cells, genetically alter them to rev up their ability to fight cancer, then reinfuse them into patients.

Taking the brakes off the immune system, Dr. Kantarjian said, can lead to life-threatening complications that require lengthy hospitalizations and expensive medications, which are prescribed in addition to conventional cancer therapy, rather than in place of it.

Keith D. Eaton, MD, a Seattle oncologist, said he ran up medical bills of $500,000 when he participated in a clinical trial of CAR T cells in 2013, even though all patients in the study received the medication for free. Dr. Eaton, who was diagnosed with acute lymphoblastic leukemia (ALL), spent nearly 2 months in the hospital.

Like Dr. Eaton, nearly half of patients who receive CAR T cells develop cytokine storm. Other serious side effects include strokelike symptoms and coma.

The cytokine storm felt like “the worst flu of your life,” said Dr. Eaton, now aged 51 years. His fever spiked so high that a hospital nurse assumed the thermometer was broken. Dr. Eaton replied, “It’s not broken. My temperature is too high to register on the thermometer.”

Although Dr. Eaton recovered, he wasn’t done with treatment. His doctors recommended a bone marrow transplant, another harrowing procedure, at a cost of hundreds of thousands of dollars.

Dr. Eaton said he feels fortunate to be healthy today, with tests showing no evidence of leukemia. His insurer paid for almost everything.

Kymriah’s sticker price is especially “outrageous” given its relatively low manufacturing costs, said Walid F. Gellad, MD, codirector of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

The gene therapy process used to create tisagenlecleucel costs about $15,000, according to a 2012 presentation by Carl H. June, MD, who pioneered CAR T-cell research at the University of Pennsylvania in Philadelphia. Dr. June could not be reached for comment.

To quell unrest about price, Novartis has offered patients and insurers a new twist on the money-back guarantee.

Novartis will charge for the drug only if patients go into remission within 1 month of treatment. In a key clinical trial, 83% of the children and young adults treated with tisagenlecleucel went into remission within 3 months. Novartis calls the plan “outcomes-based pricing.”

Novartis is “working through the specific details” of how the pricing plan will affect the Centers for Medicare & Medicaid Services, which pays for care for many cancer patients, company spokesperson Julie Masow said. “There are many hurdles” to this type of pricing plan but, Ms. Masow said, “Novartis is committed to making this happen.”

She also said that Kymriah’s manufacturing costs are much higher than $15,000, although she didn’t cite a specific dollar amount. She noted that Novartis has invested heavily in the technology, designing “an innovative manufacturing facility and process specifically for cellular therapies.”

As for Kymriah-related hospital and medication charges, “costs will vary from patient to patient and treatment center to treatment center, based on the level of care each patient requires,” Ms. Masow said. “Kymriah is a one-time treatment that has shown remarkable early, deep, and durable responses in these children who are very sick and often out of options.”

Some doctors said tisagenlecleucel, which could be used by about 600 patients a year, offers an incalculable benefit for desperately ill young people. The drug is approved for children and young adults with B-cell ALL who already have been treated with at least two other cancer therapies.

“A kid’s life is priceless,” said Michelle Hermiston, MD, director of pediatric immunotherapy at Benioff Children’s Hospital, at the University of California, San Francisco. “Any given kid has the potential to make financial impacts over a lifetime that far outweigh the cost of their cure. From this perspective, every child in my mind deserves the best curative therapy we can offer.”

Other cancer doctors say the Novartis plan is no bargain.

About 36% of patients who go into remission with tisagenlecleucel relapse within 1 year, said Vinay Prasad, MD, of Oregon Health & Science University, Portland. Many of these patients will need additional treatment, said Dr. Prasad, who wrote an editorial about tisagenlecleucel’s price Oct. 4 in Nature.

“If you’ve paid half a million dollars for drugs and half a million dollars for care, and a year later your cancer is back, is that a good deal?” asked Dr. Saltz, who cowrote a recent editorial on tisagenlecleucel’s price in JAMA.

Steve Miller, MD, chief medical officer for Express Scripts, said it would be more fair to judge Kymriah’s success after 6 months of treatment, rather than 1 month. Dr. Prasad goes even further. He said Novartis should issue refunds for any patient who relapses within 3 years.

A consumer-advocate group called Patients for Affordable Drugs also has said that tisagenlecleucel costs too much, given that the federal government spent more than $200 million over 2 decades to support the basic research into CAR T-cell therapy, long before Novartis bought the rights.

Rep. Lloyd Doggett (D-Texas) wrote a letter to the Medicare program’s director last month asking for details on how the Novartis payment deal will work.

“As Big Pharma continues to put price gouging before patient access, companies will point more and more proudly at their pricing agreements,” Rep. Doggett wrote. “But taxpayers deserve to know more about how these agreements will work – whether they will actually save the government money, defray these massive costs, and ensure that they can access lifesaving medications.”
 

KHN’s coverage related to aging & improving care of older adults is supported by The John A. Hartford Foundation. Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.

PHILADELPHIA – The updated hormone therapy position statement from the North American Menopause Society tells clinicians to move away from “lowest dose for the shortest time” and toward prescribing the appropriate dose, formulation, and route of administration to meet treatment goals.

At the group’s annual meeting, some of the authors of the position statement outlined the latest evidence for the safety of hormone therapy and special clinical considerations based on age or time of menopause and unique health risks like breast cancer. Additionally, the authors said there should not be an arbitrary “stop date” for hormone therapy.

The authors also discussed the risks of using compounded bioidentical hormones to treat menopausal symptoms.

This roundtable discussion includes JoAnn V. Pinkerton, MD, NAMS executive director and professor of obstetrics and gynecology at the University of Virginia, Charlottesville; Andrew Kaunitz, MD, associate chairman of the department of obstetrics and gynecology at the University of Florida, Jacksonville; and Cynthia A. Stuenkel, MD, clinical professor of medicine at the University of California, San Diego.

Dr. Pinkerton reported institutional research support from TherapeuticsMD. Dr. Kaunitz reported consultant/advisory board work for Allergan, Amag Pharmaceuticals, Bayer, Mithra Pharmaceuticals, Pfizer, and Shionogi. He has also received grant/research support from Bayer, Radius Health, TherapeuticsMD, and Millendo Therapeutics. Dr. Stuenkel reported having no financial disclosures.

[email protected]

On Twitter @maryellenny

PHILADELPHIA – The updated hormone therapy position statement from the North American Menopause Society tells clinicians to move away from “lowest dose for the shortest time” and toward prescribing the appropriate dose, formulation, and route of administration to meet treatment goals.

At the group’s annual meeting, some of the authors of the position statement outlined the latest evidence for the safety of hormone therapy and special clinical considerations based on age or time of menopause and unique health risks like breast cancer. Additionally, the authors said there should not be an arbitrary “stop date” for hormone therapy.

The authors also discussed the risks of using compounded bioidentical hormones to treat menopausal symptoms.

This roundtable discussion includes JoAnn V. Pinkerton, MD, NAMS executive director and professor of obstetrics and gynecology at the University of Virginia, Charlottesville; Andrew Kaunitz, MD, associate chairman of the department of obstetrics and gynecology at the University of Florida, Jacksonville; and Cynthia A. Stuenkel, MD, clinical professor of medicine at the University of California, San Diego.

Dr. Pinkerton reported institutional research support from TherapeuticsMD. Dr. Kaunitz reported consultant/advisory board work for Allergan, Amag Pharmaceuticals, Bayer, Mithra Pharmaceuticals, Pfizer, and Shionogi. He has also received grant/research support from Bayer, Radius Health, TherapeuticsMD, and Millendo Therapeutics. Dr. Stuenkel reported having no financial disclosures.

[email protected]

On Twitter @maryellenny

PHILADELPHIA – The updated hormone therapy position statement from the North American Menopause Society tells clinicians to move away from “lowest dose for the shortest time” and toward prescribing the appropriate dose, formulation, and route of administration to meet treatment goals.

At the group’s annual meeting, some of the authors of the position statement outlined the latest evidence for the safety of hormone therapy and special clinical considerations based on age or time of menopause and unique health risks like breast cancer. Additionally, the authors said there should not be an arbitrary “stop date” for hormone therapy.

The authors also discussed the risks of using compounded bioidentical hormones to treat menopausal symptoms.

This roundtable discussion includes JoAnn V. Pinkerton, MD, NAMS executive director and professor of obstetrics and gynecology at the University of Virginia, Charlottesville; Andrew Kaunitz, MD, associate chairman of the department of obstetrics and gynecology at the University of Florida, Jacksonville; and Cynthia A. Stuenkel, MD, clinical professor of medicine at the University of California, San Diego.

Dr. Pinkerton reported institutional research support from TherapeuticsMD. Dr. Kaunitz reported consultant/advisory board work for Allergan, Amag Pharmaceuticals, Bayer, Mithra Pharmaceuticals, Pfizer, and Shionogi. He has also received grant/research support from Bayer, Radius Health, TherapeuticsMD, and Millendo Therapeutics. Dr. Stuenkel reported having no financial disclosures.

[email protected]

On Twitter @maryellenny

In patients with localized clear cell renal cell carcinoma (RCC), tumor levels of the oncogenic protein EZH2 (enhancer of zeste homolog 2) were predictive of risk of RCC-specific death, including in patients considered at low or intermediate risk by a standard prognostic model.

Among nearly 2,000 tumors from patients with RCC in three different cohorts, the risks of both all-cause mortality and RCC-specific death were approximately double for patients with tumors that had high expression of EZH2 compared with those whose tumors expressed only low levels, reported Thai Huu Ho, MD, PhD, from the Mayo Clinic in Phoenix, and colleagues.

Among patients deemed to be at low risk according to the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score, high levels of EZH2 were associated with a sixfold increase in risk of death, the investigators wrote (J Clin Oncol. 2017 Oct 4. doi: 10.1200/JCO.2017.73.3238).

“With the increasing incidence of small RCC tumors detected by cross-sectional imaging, our study emphasizes the clinical utility of a biomarker that is compatible with a single FFPE [formalin-fixed, paraffin-embedded] slide that accurately predicts risk of RCC death beyond existing clinicopathologic models” they wrote.

EZH2 is a chromatin remodeler, a member of a family of proteins that are involved in epigenetic gene silencing. Although previous studies have explored potential associations between EZH2 expression and RCC outcomes, results have been conflicting, Dr. Ho and associates noted.

In hopes of getting a more definitive picture of the potential role of EZH2 as a prognostic biomarker for RCC, the investigators looked at the association between EZH2 expression and survival in tumors from 532 patients in the Cancer Genome Atlas (CGA) cohort, 122 patients from a University of Texas Southwestern Medical Center (Dallas) cohort, and from 1,338 patients in a Mayo Clinic cohort.

In a model adjusted for age and SSIGN score, patients in the CGA cohort whose tumors had high levels of EZH2 expression had a hazard ratio (HR) for worse overall survival of 1.54 (P less than .028) compared with patients with low expression. Respective HRs for overall survival in the UT Southwestern and Mayo Cohorts were 2.16 (P = .034) and 1.43 (P = .00026).

When the researchers looked at RCC-specific survival in patients in the Mayo cohort, they found that those with the highest levels of EZH2 expression had a twofold risk for death vs. those with the lowest levels (HR 1.97, P less than .001).

They also found that patients with a low-risk SSIGN score who had high levels of EZH2 protein expression had an HR for RCC-specific death of 6.14, and that patients with intermediate-risk SSIGN scores has an HR for RCC-related death of 2.12 (P less than .001 for both comparisons).

The investigators noted that EZH2 enzymatic activity in RCC could potentially be targeted by EZH2 inhibitors such as tazemetostat.

“Further studies are required to determine how to better incorporate molecular biomarkers with prognostic information into surveillance guidelines and adjuvant clinical trials,” they concluded.

The study was supported by the Mayo Clinic, Gerstner Family Career Development Award, National Cancer Institute, and Cancer Prevention Research Institute of Texas. Dr. Ho and seven coauthors reported no relationships to disclose. The remaining investigators reported relationships with various companies.

[email protected]

In patients with localized clear cell renal cell carcinoma (RCC), tumor levels of the oncogenic protein EZH2 (enhancer of zeste homolog 2) were predictive of risk of RCC-specific death, including in patients considered at low or intermediate risk by a standard prognostic model.

Among nearly 2,000 tumors from patients with RCC in three different cohorts, the risks of both all-cause mortality and RCC-specific death were approximately double for patients with tumors that had high expression of EZH2 compared with those whose tumors expressed only low levels, reported Thai Huu Ho, MD, PhD, from the Mayo Clinic in Phoenix, and colleagues.

Among patients deemed to be at low risk according to the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score, high levels of EZH2 were associated with a sixfold increase in risk of death, the investigators wrote (J Clin Oncol. 2017 Oct 4. doi: 10.1200/JCO.2017.73.3238).

“With the increasing incidence of small RCC tumors detected by cross-sectional imaging, our study emphasizes the clinical utility of a biomarker that is compatible with a single FFPE [formalin-fixed, paraffin-embedded] slide that accurately predicts risk of RCC death beyond existing clinicopathologic models” they wrote.

EZH2 is a chromatin remodeler, a member of a family of proteins that are involved in epigenetic gene silencing. Although previous studies have explored potential associations between EZH2 expression and RCC outcomes, results have been conflicting, Dr. Ho and associates noted.

In hopes of getting a more definitive picture of the potential role of EZH2 as a prognostic biomarker for RCC, the investigators looked at the association between EZH2 expression and survival in tumors from 532 patients in the Cancer Genome Atlas (CGA) cohort, 122 patients from a University of Texas Southwestern Medical Center (Dallas) cohort, and from 1,338 patients in a Mayo Clinic cohort.

In a model adjusted for age and SSIGN score, patients in the CGA cohort whose tumors had high levels of EZH2 expression had a hazard ratio (HR) for worse overall survival of 1.54 (P less than .028) compared with patients with low expression. Respective HRs for overall survival in the UT Southwestern and Mayo Cohorts were 2.16 (P = .034) and 1.43 (P = .00026).

When the researchers looked at RCC-specific survival in patients in the Mayo cohort, they found that those with the highest levels of EZH2 expression had a twofold risk for death vs. those with the lowest levels (HR 1.97, P less than .001).

They also found that patients with a low-risk SSIGN score who had high levels of EZH2 protein expression had an HR for RCC-specific death of 6.14, and that patients with intermediate-risk SSIGN scores has an HR for RCC-related death of 2.12 (P less than .001 for both comparisons).

The investigators noted that EZH2 enzymatic activity in RCC could potentially be targeted by EZH2 inhibitors such as tazemetostat.

“Further studies are required to determine how to better incorporate molecular biomarkers with prognostic information into surveillance guidelines and adjuvant clinical trials,” they concluded.

The study was supported by the Mayo Clinic, Gerstner Family Career Development Award, National Cancer Institute, and Cancer Prevention Research Institute of Texas. Dr. Ho and seven coauthors reported no relationships to disclose. The remaining investigators reported relationships with various companies.

[email protected]

In patients with localized clear cell renal cell carcinoma (RCC), tumor levels of the oncogenic protein EZH2 (enhancer of zeste homolog 2) were predictive of risk of RCC-specific death, including in patients considered at low or intermediate risk by a standard prognostic model.

Among nearly 2,000 tumors from patients with RCC in three different cohorts, the risks of both all-cause mortality and RCC-specific death were approximately double for patients with tumors that had high expression of EZH2 compared with those whose tumors expressed only low levels, reported Thai Huu Ho, MD, PhD, from the Mayo Clinic in Phoenix, and colleagues.

Among patients deemed to be at low risk according to the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score, high levels of EZH2 were associated with a sixfold increase in risk of death, the investigators wrote (J Clin Oncol. 2017 Oct 4. doi: 10.1200/JCO.2017.73.3238).

“With the increasing incidence of small RCC tumors detected by cross-sectional imaging, our study emphasizes the clinical utility of a biomarker that is compatible with a single FFPE [formalin-fixed, paraffin-embedded] slide that accurately predicts risk of RCC death beyond existing clinicopathologic models” they wrote.

EZH2 is a chromatin remodeler, a member of a family of proteins that are involved in epigenetic gene silencing. Although previous studies have explored potential associations between EZH2 expression and RCC outcomes, results have been conflicting, Dr. Ho and associates noted.

In hopes of getting a more definitive picture of the potential role of EZH2 as a prognostic biomarker for RCC, the investigators looked at the association between EZH2 expression and survival in tumors from 532 patients in the Cancer Genome Atlas (CGA) cohort, 122 patients from a University of Texas Southwestern Medical Center (Dallas) cohort, and from 1,338 patients in a Mayo Clinic cohort.

In a model adjusted for age and SSIGN score, patients in the CGA cohort whose tumors had high levels of EZH2 expression had a hazard ratio (HR) for worse overall survival of 1.54 (P less than .028) compared with patients with low expression. Respective HRs for overall survival in the UT Southwestern and Mayo Cohorts were 2.16 (P = .034) and 1.43 (P = .00026).

When the researchers looked at RCC-specific survival in patients in the Mayo cohort, they found that those with the highest levels of EZH2 expression had a twofold risk for death vs. those with the lowest levels (HR 1.97, P less than .001).

They also found that patients with a low-risk SSIGN score who had high levels of EZH2 protein expression had an HR for RCC-specific death of 6.14, and that patients with intermediate-risk SSIGN scores has an HR for RCC-related death of 2.12 (P less than .001 for both comparisons).

The investigators noted that EZH2 enzymatic activity in RCC could potentially be targeted by EZH2 inhibitors such as tazemetostat.

“Further studies are required to determine how to better incorporate molecular biomarkers with prognostic information into surveillance guidelines and adjuvant clinical trials,” they concluded.

The study was supported by the Mayo Clinic, Gerstner Family Career Development Award, National Cancer Institute, and Cancer Prevention Research Institute of Texas. Dr. Ho and seven coauthors reported no relationships to disclose. The remaining investigators reported relationships with various companies.

[email protected]

PHILADELPHIA – Despite the slow start that flibanserin had since being approved to treat hypoactive sexual desire disorder (HSDD) in premenopausal women in 2015, more drugs are in the pipeline to help women address low desire.

One drug – bremelanotide – has completed phase 3 trials and could be considered by the Food and Drug Administration as early as 2018, Sheryl A. Kingsberg, PhD, said during an interview at the annual meeting of the North American Menopause Society.

Bremelanotide is a first-in-class melanocortin receptor 4 agonist being developed for premenopausal women to use on an as-needed basis and is delivered using a single-dose, auto injector.

Another drug, prasterone, is also being studied to treat HSDD. The intravaginal DHEA treatment is already approved to treat dyspareunia due to vulvovaginal atrophy in menopause. The manufacturer is beginning phase 3 trials for HSDD in postmenopausal women, said Dr. Kingsberg, who is chief of the division of behavioral medicine at MacDonald Women’s Hospital/University Hospitals Cleveland Medical Center and the president of NAMS.

Additional drugs are in earlier stages of development for HSDD. While flibanserin hasn’t been a blockbuster drug, its approval by the FDA paved the way for additional drug development in this area, Dr. Kingsberg said.

Dr. Kingsberg reported consultant/advisory board work for Amag Pharmaceuticals, Duchesnay, Emotional Brain, EndoCeutics, Materna Medical, Palatin Technologies, Pfizer, Shionogi, TherapeuticsMD, Valeant Pharmaceuticals, and Viveve. She is on the speakers bureau for Valeant Pharmaceuticals and owns stock in Viveve.

[email protected]

On Twitter @maryellenny

PHILADELPHIA – Despite the slow start that flibanserin had since being approved to treat hypoactive sexual desire disorder (HSDD) in premenopausal women in 2015, more drugs are in the pipeline to help women address low desire.

One drug – bremelanotide – has completed phase 3 trials and could be considered by the Food and Drug Administration as early as 2018, Sheryl A. Kingsberg, PhD, said during an interview at the annual meeting of the North American Menopause Society.

Bremelanotide is a first-in-class melanocortin receptor 4 agonist being developed for premenopausal women to use on an as-needed basis and is delivered using a single-dose, auto injector.

Another drug, prasterone, is also being studied to treat HSDD. The intravaginal DHEA treatment is already approved to treat dyspareunia due to vulvovaginal atrophy in menopause. The manufacturer is beginning phase 3 trials for HSDD in postmenopausal women, said Dr. Kingsberg, who is chief of the division of behavioral medicine at MacDonald Women’s Hospital/University Hospitals Cleveland Medical Center and the president of NAMS.

Additional drugs are in earlier stages of development for HSDD. While flibanserin hasn’t been a blockbuster drug, its approval by the FDA paved the way for additional drug development in this area, Dr. Kingsberg said.

Dr. Kingsberg reported consultant/advisory board work for Amag Pharmaceuticals, Duchesnay, Emotional Brain, EndoCeutics, Materna Medical, Palatin Technologies, Pfizer, Shionogi, TherapeuticsMD, Valeant Pharmaceuticals, and Viveve. She is on the speakers bureau for Valeant Pharmaceuticals and owns stock in Viveve.

[email protected]

On Twitter @maryellenny

PHILADELPHIA – Despite the slow start that flibanserin had since being approved to treat hypoactive sexual desire disorder (HSDD) in premenopausal women in 2015, more drugs are in the pipeline to help women address low desire.

One drug – bremelanotide – has completed phase 3 trials and could be considered by the Food and Drug Administration as early as 2018, Sheryl A. Kingsberg, PhD, said during an interview at the annual meeting of the North American Menopause Society.

Bremelanotide is a first-in-class melanocortin receptor 4 agonist being developed for premenopausal women to use on an as-needed basis and is delivered using a single-dose, auto injector.

Another drug, prasterone, is also being studied to treat HSDD. The intravaginal DHEA treatment is already approved to treat dyspareunia due to vulvovaginal atrophy in menopause. The manufacturer is beginning phase 3 trials for HSDD in postmenopausal women, said Dr. Kingsberg, who is chief of the division of behavioral medicine at MacDonald Women’s Hospital/University Hospitals Cleveland Medical Center and the president of NAMS.

Additional drugs are in earlier stages of development for HSDD. While flibanserin hasn’t been a blockbuster drug, its approval by the FDA paved the way for additional drug development in this area, Dr. Kingsberg said.

Dr. Kingsberg reported consultant/advisory board work for Amag Pharmaceuticals, Duchesnay, Emotional Brain, EndoCeutics, Materna Medical, Palatin Technologies, Pfizer, Shionogi, TherapeuticsMD, Valeant Pharmaceuticals, and Viveve. She is on the speakers bureau for Valeant Pharmaceuticals and owns stock in Viveve.

[email protected]

On Twitter @maryellenny

PHILADELPHIA – Andrew Kaunitz, MD, the chair of the 2017 scientific program committee for the annual meeting of the North American Menopause Society, shared his top take-home messages from the meeting.

New anabolic medications that increase bone mineral density and dramatically reduce fracture risk are in the pipeline, Dr. Kaunitz, a professor in the department of obstetrics and gynecology at the University of Florida, Jacksonville, said in a video interview.

Another finding from the meeting is that type 2 diabetes, despite being associated with an increased body mass index, actually elevates a woman’s risk for fracture. “That was something new for me, and I think it was something new for a lot of the practitioners attending the NAMS meeting,” Dr. Kaunitz said.

The meeting also offered tips for managing polycystic ovarian syndrome in women who are in midlife, including the importance of screening for diabetes and assessing for lipid disorders. Additionally, attendees learned about the management of migraines in menopausal women and older reproductive-age women.

A well-attended session on breast imaging explored how breast tomosynthesis can reduce false positives and recalls, as well as how new technology can reduce the radiation exposure associated with tomosynthesis. The session also featured evidence that screening mammography has lower-than-reported sensitivity, but offered a hopeful note on the promise of improved sensitivity through molecular breast imaging.

Dr. Kaunitz reported consultant/advisory board work for Allergan, Amag Pharmaceuticals, Bayer, Mithra Pharmaceuticals, Pfizer, and Shionogi. He has received grant/research support from Bayer, Radius Health, TherapeuticsMD, and Millendo Therapeutics.

[email protected]

On Twitter @maryellenny

PHILADELPHIA – Andrew Kaunitz, MD, the chair of the 2017 scientific program committee for the annual meeting of the North American Menopause Society, shared his top take-home messages from the meeting.

New anabolic medications that increase bone mineral density and dramatically reduce fracture risk are in the pipeline, Dr. Kaunitz, a professor in the department of obstetrics and gynecology at the University of Florida, Jacksonville, said in a video interview.

Another finding from the meeting is that type 2 diabetes, despite being associated with an increased body mass index, actually elevates a woman’s risk for fracture. “That was something new for me, and I think it was something new for a lot of the practitioners attending the NAMS meeting,” Dr. Kaunitz said.

The meeting also offered tips for managing polycystic ovarian syndrome in women who are in midlife, including the importance of screening for diabetes and assessing for lipid disorders. Additionally, attendees learned about the management of migraines in menopausal women and older reproductive-age women.

A well-attended session on breast imaging explored how breast tomosynthesis can reduce false positives and recalls, as well as how new technology can reduce the radiation exposure associated with tomosynthesis. The session also featured evidence that screening mammography has lower-than-reported sensitivity, but offered a hopeful note on the promise of improved sensitivity through molecular breast imaging.

Dr. Kaunitz reported consultant/advisory board work for Allergan, Amag Pharmaceuticals, Bayer, Mithra Pharmaceuticals, Pfizer, and Shionogi. He has received grant/research support from Bayer, Radius Health, TherapeuticsMD, and Millendo Therapeutics.

[email protected]

On Twitter @maryellenny

PHILADELPHIA – Andrew Kaunitz, MD, the chair of the 2017 scientific program committee for the annual meeting of the North American Menopause Society, shared his top take-home messages from the meeting.

New anabolic medications that increase bone mineral density and dramatically reduce fracture risk are in the pipeline, Dr. Kaunitz, a professor in the department of obstetrics and gynecology at the University of Florida, Jacksonville, said in a video interview.

Another finding from the meeting is that type 2 diabetes, despite being associated with an increased body mass index, actually elevates a woman’s risk for fracture. “That was something new for me, and I think it was something new for a lot of the practitioners attending the NAMS meeting,” Dr. Kaunitz said.

The meeting also offered tips for managing polycystic ovarian syndrome in women who are in midlife, including the importance of screening for diabetes and assessing for lipid disorders. Additionally, attendees learned about the management of migraines in menopausal women and older reproductive-age women.

A well-attended session on breast imaging explored how breast tomosynthesis can reduce false positives and recalls, as well as how new technology can reduce the radiation exposure associated with tomosynthesis. The session also featured evidence that screening mammography has lower-than-reported sensitivity, but offered a hopeful note on the promise of improved sensitivity through molecular breast imaging.

Dr. Kaunitz reported consultant/advisory board work for Allergan, Amag Pharmaceuticals, Bayer, Mithra Pharmaceuticals, Pfizer, and Shionogi. He has received grant/research support from Bayer, Radius Health, TherapeuticsMD, and Millendo Therapeutics.

[email protected]

On Twitter @maryellenny