Susan London

SAN FRANCISCO – Delaying initiation of renal replacement therapy in critically ill patients with severe acute kidney injury appears to be not only safe but beneficial, according to a randomized controlled trial conducted in France.

The trial, known as Artificial Kidney Initiation in Kidney Injury (AKIKI), was conducted among 620 adult patients from 31 intensive care units. The investigators were led by Dr. Stéphane Gaudry of Assistance Publique–Hôpitaux de Paris.

The death rate did not differ significantly between groups assigned to an early versus a late initiation strategy, according to results presented at an international conference of the American Thoracic Society and simultaneously published (N Engl J Med. 2016 May 15. doi: 10.1056/NEJMoa1603017).

Moreover, nearly half of the patients in the delayed initiation group were able to avoid renal replacement therapy. And they were less likely to develop bloodstream infections and had more rapid onset of diuresis (heralding recovery of renal function) than did peers in whom the therapy was initiated early.

“Our study should not be interpreted as suggesting that a ‘wait and see’ approach is safe for all patients. Indeed, careful surveillance is mandatory when deciding to delay renal-replacement therapy in patients with severe acute kidney injury so that any complications will be detected and renal-replacement therapy initiated without delay,” the investigators concluded. “In our trial, delaying the initiation of therapy allowed many patients to recover from acute kidney injury without embarking on such a treatment course.”

Further, the “findings may not be generalizable, because more than 50% of the patients in our trial received intermittent hemodialysis as the first method of therapy and only 30% of the patients received continuous renal-replacement therapy as the sole method (with no intermittent dialysis at any time).”

The author of an accompanying editorial, Dr. Ravindra L. Mehta of the University of California, San Diego, lists some caveats in interpreting the trial’s findings as support for the delayed initiation strategy.

For example, he notes, the longer time to initiation with the delayed strategy contributed to worsening of metabolic and clinical status in the patients who ultimately did need therapy; the study did not assess the development of chronic kidney disease; and the types of renal replacement therapy selected for patients seem “surprising” as the majority put on this therapy needed vasopressors.

“The findings highlight a need for dynamic risk-stratification tools to identify patients who will not need renal-replacement therapy for management of their acute kidney injury,” Dr. Mehta concluded, noting that ongoing studies should help inform management in this area. “Meanwhile, we should focus on the timely application of renal-replacement therapy while considering individual patient characteristics, process-of-care elements, and logistics to achieve therapeutic goals …”

Patients were eligible for the trial if they had severe acute kidney injury, defined as Kidney Disease: Improving Global Outcomes (KDIGO) stage 3; required mechanical ventilation, catecholamine infusion, or both; and did not have a potentially life-threatening complication directly related to renal failure.

In those assigned to the early strategy, renal replacement therapy was started immediately after randomization. In those assigned to the delayed strategy, it was started if any of several criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg/dL, or oliguria for more than 72 hours after randomization. The specific type of renal replacement therapy was left up to each study site.

The median time between randomization and initiation of renal replacement therapy was 2 hours in the early strategy group and 57 hours in the delayed strategy group.

The estimated 60-day mortality rate – the trial’s primary outcome – was 48.5% with early initiation of therapy and 49.7% with delayed initiation, a nonsignificant difference.

Fully 49% of patients in the delayed strategy group never received renal replacement therapy. In addition, patients in this group were half as likely as were peers in the early initiation group to develop a bloodstream infection (5% vs. 10%), and they had more rapid onset of diuresis (P less than .001).

The groups were essentially the same with respect to the rate of gastrointestinal bleeding and the lengths of stay in the intensive care unit and in the hospital.

Dr. Gaudry disclosed that he received grant support from the French Ministry of Health during the study, and from XENIOS France outside the research. The trial was supported by a grant from Programme Hospitalier de Recherche Clinique National, 2012 (AOM12456), funded by the French Ministry of Health..

SAN FRANCISCO – Delaying initiation of renal replacement therapy in critically ill patients with severe acute kidney injury appears to be not only safe but beneficial, according to a randomized controlled trial conducted in France.

The trial, known as Artificial Kidney Initiation in Kidney Injury (AKIKI), was conducted among 620 adult patients from 31 intensive care units. The investigators were led by Dr. Stéphane Gaudry of Assistance Publique–Hôpitaux de Paris.

The death rate did not differ significantly between groups assigned to an early versus a late initiation strategy, according to results presented at an international conference of the American Thoracic Society and simultaneously published (N Engl J Med. 2016 May 15. doi: 10.1056/NEJMoa1603017).

Moreover, nearly half of the patients in the delayed initiation group were able to avoid renal replacement therapy. And they were less likely to develop bloodstream infections and had more rapid onset of diuresis (heralding recovery of renal function) than did peers in whom the therapy was initiated early.

“Our study should not be interpreted as suggesting that a ‘wait and see’ approach is safe for all patients. Indeed, careful surveillance is mandatory when deciding to delay renal-replacement therapy in patients with severe acute kidney injury so that any complications will be detected and renal-replacement therapy initiated without delay,” the investigators concluded. “In our trial, delaying the initiation of therapy allowed many patients to recover from acute kidney injury without embarking on such a treatment course.”

Further, the “findings may not be generalizable, because more than 50% of the patients in our trial received intermittent hemodialysis as the first method of therapy and only 30% of the patients received continuous renal-replacement therapy as the sole method (with no intermittent dialysis at any time).”

The author of an accompanying editorial, Dr. Ravindra L. Mehta of the University of California, San Diego, lists some caveats in interpreting the trial’s findings as support for the delayed initiation strategy.

For example, he notes, the longer time to initiation with the delayed strategy contributed to worsening of metabolic and clinical status in the patients who ultimately did need therapy; the study did not assess the development of chronic kidney disease; and the types of renal replacement therapy selected for patients seem “surprising” as the majority put on this therapy needed vasopressors.

“The findings highlight a need for dynamic risk-stratification tools to identify patients who will not need renal-replacement therapy for management of their acute kidney injury,” Dr. Mehta concluded, noting that ongoing studies should help inform management in this area. “Meanwhile, we should focus on the timely application of renal-replacement therapy while considering individual patient characteristics, process-of-care elements, and logistics to achieve therapeutic goals …”

Patients were eligible for the trial if they had severe acute kidney injury, defined as Kidney Disease: Improving Global Outcomes (KDIGO) stage 3; required mechanical ventilation, catecholamine infusion, or both; and did not have a potentially life-threatening complication directly related to renal failure.

In those assigned to the early strategy, renal replacement therapy was started immediately after randomization. In those assigned to the delayed strategy, it was started if any of several criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg/dL, or oliguria for more than 72 hours after randomization. The specific type of renal replacement therapy was left up to each study site.

The median time between randomization and initiation of renal replacement therapy was 2 hours in the early strategy group and 57 hours in the delayed strategy group.

The estimated 60-day mortality rate – the trial’s primary outcome – was 48.5% with early initiation of therapy and 49.7% with delayed initiation, a nonsignificant difference.

Fully 49% of patients in the delayed strategy group never received renal replacement therapy. In addition, patients in this group were half as likely as were peers in the early initiation group to develop a bloodstream infection (5% vs. 10%), and they had more rapid onset of diuresis (P less than .001).

The groups were essentially the same with respect to the rate of gastrointestinal bleeding and the lengths of stay in the intensive care unit and in the hospital.

Dr. Gaudry disclosed that he received grant support from the French Ministry of Health during the study, and from XENIOS France outside the research. The trial was supported by a grant from Programme Hospitalier de Recherche Clinique National, 2012 (AOM12456), funded by the French Ministry of Health..

SAN FRANCISCO – Delaying initiation of renal replacement therapy in critically ill patients with severe acute kidney injury appears to be not only safe but beneficial, according to a randomized controlled trial conducted in France.

The trial, known as Artificial Kidney Initiation in Kidney Injury (AKIKI), was conducted among 620 adult patients from 31 intensive care units. The investigators were led by Dr. Stéphane Gaudry of Assistance Publique–Hôpitaux de Paris.

The death rate did not differ significantly between groups assigned to an early versus a late initiation strategy, according to results presented at an international conference of the American Thoracic Society and simultaneously published (N Engl J Med. 2016 May 15. doi: 10.1056/NEJMoa1603017).

Moreover, nearly half of the patients in the delayed initiation group were able to avoid renal replacement therapy. And they were less likely to develop bloodstream infections and had more rapid onset of diuresis (heralding recovery of renal function) than did peers in whom the therapy was initiated early.

“Our study should not be interpreted as suggesting that a ‘wait and see’ approach is safe for all patients. Indeed, careful surveillance is mandatory when deciding to delay renal-replacement therapy in patients with severe acute kidney injury so that any complications will be detected and renal-replacement therapy initiated without delay,” the investigators concluded. “In our trial, delaying the initiation of therapy allowed many patients to recover from acute kidney injury without embarking on such a treatment course.”

Further, the “findings may not be generalizable, because more than 50% of the patients in our trial received intermittent hemodialysis as the first method of therapy and only 30% of the patients received continuous renal-replacement therapy as the sole method (with no intermittent dialysis at any time).”

The author of an accompanying editorial, Dr. Ravindra L. Mehta of the University of California, San Diego, lists some caveats in interpreting the trial’s findings as support for the delayed initiation strategy.

For example, he notes, the longer time to initiation with the delayed strategy contributed to worsening of metabolic and clinical status in the patients who ultimately did need therapy; the study did not assess the development of chronic kidney disease; and the types of renal replacement therapy selected for patients seem “surprising” as the majority put on this therapy needed vasopressors.

“The findings highlight a need for dynamic risk-stratification tools to identify patients who will not need renal-replacement therapy for management of their acute kidney injury,” Dr. Mehta concluded, noting that ongoing studies should help inform management in this area. “Meanwhile, we should focus on the timely application of renal-replacement therapy while considering individual patient characteristics, process-of-care elements, and logistics to achieve therapeutic goals …”

Patients were eligible for the trial if they had severe acute kidney injury, defined as Kidney Disease: Improving Global Outcomes (KDIGO) stage 3; required mechanical ventilation, catecholamine infusion, or both; and did not have a potentially life-threatening complication directly related to renal failure.

In those assigned to the early strategy, renal replacement therapy was started immediately after randomization. In those assigned to the delayed strategy, it was started if any of several criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg/dL, or oliguria for more than 72 hours after randomization. The specific type of renal replacement therapy was left up to each study site.

The median time between randomization and initiation of renal replacement therapy was 2 hours in the early strategy group and 57 hours in the delayed strategy group.

The estimated 60-day mortality rate – the trial’s primary outcome – was 48.5% with early initiation of therapy and 49.7% with delayed initiation, a nonsignificant difference.

Fully 49% of patients in the delayed strategy group never received renal replacement therapy. In addition, patients in this group were half as likely as were peers in the early initiation group to develop a bloodstream infection (5% vs. 10%), and they had more rapid onset of diuresis (P less than .001).

The groups were essentially the same with respect to the rate of gastrointestinal bleeding and the lengths of stay in the intensive care unit and in the hospital.

Dr. Gaudry disclosed that he received grant support from the French Ministry of Health during the study, and from XENIOS France outside the research. The trial was supported by a grant from Programme Hospitalier de Recherche Clinique National, 2012 (AOM12456), funded by the French Ministry of Health..

VANCOUVER – The antioxidant edaravone was associated with less deterioration in functional rating and quality of life scales when started early in the course of amyotrophic lateral sclerosis (ALS), based on results from a set of trials conducted in Japan and reported at the annual meeting of the American Academy of Neurology.

Edaravone is thought to confer neuroprotection in part through its free radical–scavenging activity and first garnered interest for the treatment of acute ischemic stroke, according to presenting author Dr. Joseph M. Palumbo, vice president and head of Clinical Research at Mitsubishi Tanabe Pharma Development America, the maker of edaravone. It is now approved in several countries for that indication.

Susan London/Frontline Medical News

In a pivotal randomized phase III trial, Dr. Palumbo and his colleagues studied 137 patients who had definite or probable ALS, were less than 2 years out from symptom onset, had normal respiratory function, and were able to perform most activities of daily living. All patients received standard of care, usually including riluzole (Rilutek), plus either edaravone (MCI-186) or placebo.

After 24 weeks of treatment, compared with placebo, edaravone was associated with a smaller decline in scores on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) (–5.01 vs. –7.50; difference between groups, 2.49; P = .0013), according to data reported in a poster session at the meeting.

Significant benefit was seen on the limb and bulbar subscales, and there was a trend favoring edaravone on the respiratory subscale. Additionally, patients given edaravone had comparatively less deterioration in quality of life as assessed with the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) (P = .03). Grip strength did not differ between groups, and there were no deaths in either group.

“We are not aware of any other positive phase III study in maybe a generation, since riluzole, in ALS. So we are showing this data and we are hopeful that people are as excited as we are,” Dr. Palumbo said in an interview.

In the area of safety, edaravone and placebo did not differ significantly with respect to the rate of adverse events, with contusion, dysphagia, and constipation predominating. The most common serious adverse event was dysphagia, seen in 12% of each group.

The trial’s findings led to approval of edaravone for treatment of ALS in Japan, where it is marketed as Radicut. Additionally, the U.S. Food and Drug Administration (FDA) granted edaravone orphan drug designation for ALS but has not approved it for this indication.

An additional 24-week open-label extension study among 123 patients from the trial, in which all received the drug regardless of their initially assigned treatment, showed that the benefit of edaravone was durable. Patients who continued treatment with the drug had less of a decline from baseline in ALSFRS-R score than did peers switched to the drug from placebo (difference between groups, 4.17; P = .004), according to data reported in another poster. Also, the former had a lower risk of death (P = .019) and less decline in lung function. Meanwhile, the drug’s safety profile remained good.

The researchers are preparing their findings for journal submission and are revisiting the drug’s regulatory status in the United States, according to Dr. Palumbo. “We’re talking to the FDA now. We’ve got our fingers crossed.”

There is no compelling reason to think that the drug’s efficacy in the U.S. population would differ from that in the Japanese population, but that will ultimately be an issue for regulators to decide, he said.

It is difficult to compare edaravone with other ALS treatment options, as all patients in the trial concomitantly received standard of care, Dr. Palumbo explained. “We can only speak about standard of care, and we think that we’ve improved on standard of care here,” he maintained.

The initial phase III trial of edaravone in ALS, which enrolled a population having a wider range of disease severity, failed to meet its primary endpoint of improvement in ALSFRS-R score (Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:610-7). An extension study in 181 patients, also reported in a poster at the meeting, supported post hoc findings hinting that the timing of drug initiation was important.

“We learned a tremendous amount in that study about who the patients were who would ultimately benefit,” Dr. Palumbo commented. “We had a number of hypotheses. One hypothesis was that if we found patients who in fact were still functional at baseline and who really had the diagnosis – they had either definite or probable ALS – and still had very good respiratory function, that we would likely find a signal there.”

Rounding out the set of trials was a small randomized placebo-controlled trial among 25 patients with more advanced ALS, done at the request of Japanese health authorities. Results showed that edaravone was safe in this population but had no clear benefit.

Dr. Palumbo disclosed that he is an employee of Mitsubishi Tanabe Pharma Development America, Inc. The trials were sponsored by Mitsubishi Tanabe Pharma Corporation.

VANCOUVER – The antioxidant edaravone was associated with less deterioration in functional rating and quality of life scales when started early in the course of amyotrophic lateral sclerosis (ALS), based on results from a set of trials conducted in Japan and reported at the annual meeting of the American Academy of Neurology.

Edaravone is thought to confer neuroprotection in part through its free radical–scavenging activity and first garnered interest for the treatment of acute ischemic stroke, according to presenting author Dr. Joseph M. Palumbo, vice president and head of Clinical Research at Mitsubishi Tanabe Pharma Development America, the maker of edaravone. It is now approved in several countries for that indication.

Susan London/Frontline Medical News

In a pivotal randomized phase III trial, Dr. Palumbo and his colleagues studied 137 patients who had definite or probable ALS, were less than 2 years out from symptom onset, had normal respiratory function, and were able to perform most activities of daily living. All patients received standard of care, usually including riluzole (Rilutek), plus either edaravone (MCI-186) or placebo.

After 24 weeks of treatment, compared with placebo, edaravone was associated with a smaller decline in scores on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) (–5.01 vs. –7.50; difference between groups, 2.49; P = .0013), according to data reported in a poster session at the meeting.

Significant benefit was seen on the limb and bulbar subscales, and there was a trend favoring edaravone on the respiratory subscale. Additionally, patients given edaravone had comparatively less deterioration in quality of life as assessed with the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) (P = .03). Grip strength did not differ between groups, and there were no deaths in either group.

“We are not aware of any other positive phase III study in maybe a generation, since riluzole, in ALS. So we are showing this data and we are hopeful that people are as excited as we are,” Dr. Palumbo said in an interview.

In the area of safety, edaravone and placebo did not differ significantly with respect to the rate of adverse events, with contusion, dysphagia, and constipation predominating. The most common serious adverse event was dysphagia, seen in 12% of each group.

The trial’s findings led to approval of edaravone for treatment of ALS in Japan, where it is marketed as Radicut. Additionally, the U.S. Food and Drug Administration (FDA) granted edaravone orphan drug designation for ALS but has not approved it for this indication.

An additional 24-week open-label extension study among 123 patients from the trial, in which all received the drug regardless of their initially assigned treatment, showed that the benefit of edaravone was durable. Patients who continued treatment with the drug had less of a decline from baseline in ALSFRS-R score than did peers switched to the drug from placebo (difference between groups, 4.17; P = .004), according to data reported in another poster. Also, the former had a lower risk of death (P = .019) and less decline in lung function. Meanwhile, the drug’s safety profile remained good.

The researchers are preparing their findings for journal submission and are revisiting the drug’s regulatory status in the United States, according to Dr. Palumbo. “We’re talking to the FDA now. We’ve got our fingers crossed.”

There is no compelling reason to think that the drug’s efficacy in the U.S. population would differ from that in the Japanese population, but that will ultimately be an issue for regulators to decide, he said.

It is difficult to compare edaravone with other ALS treatment options, as all patients in the trial concomitantly received standard of care, Dr. Palumbo explained. “We can only speak about standard of care, and we think that we’ve improved on standard of care here,” he maintained.

The initial phase III trial of edaravone in ALS, which enrolled a population having a wider range of disease severity, failed to meet its primary endpoint of improvement in ALSFRS-R score (Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:610-7). An extension study in 181 patients, also reported in a poster at the meeting, supported post hoc findings hinting that the timing of drug initiation was important.

“We learned a tremendous amount in that study about who the patients were who would ultimately benefit,” Dr. Palumbo commented. “We had a number of hypotheses. One hypothesis was that if we found patients who in fact were still functional at baseline and who really had the diagnosis – they had either definite or probable ALS – and still had very good respiratory function, that we would likely find a signal there.”

Rounding out the set of trials was a small randomized placebo-controlled trial among 25 patients with more advanced ALS, done at the request of Japanese health authorities. Results showed that edaravone was safe in this population but had no clear benefit.

Dr. Palumbo disclosed that he is an employee of Mitsubishi Tanabe Pharma Development America, Inc. The trials were sponsored by Mitsubishi Tanabe Pharma Corporation.

VANCOUVER – The antioxidant edaravone was associated with less deterioration in functional rating and quality of life scales when started early in the course of amyotrophic lateral sclerosis (ALS), based on results from a set of trials conducted in Japan and reported at the annual meeting of the American Academy of Neurology.

Edaravone is thought to confer neuroprotection in part through its free radical–scavenging activity and first garnered interest for the treatment of acute ischemic stroke, according to presenting author Dr. Joseph M. Palumbo, vice president and head of Clinical Research at Mitsubishi Tanabe Pharma Development America, the maker of edaravone. It is now approved in several countries for that indication.

Susan London/Frontline Medical News

In a pivotal randomized phase III trial, Dr. Palumbo and his colleagues studied 137 patients who had definite or probable ALS, were less than 2 years out from symptom onset, had normal respiratory function, and were able to perform most activities of daily living. All patients received standard of care, usually including riluzole (Rilutek), plus either edaravone (MCI-186) or placebo.

After 24 weeks of treatment, compared with placebo, edaravone was associated with a smaller decline in scores on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) (–5.01 vs. –7.50; difference between groups, 2.49; P = .0013), according to data reported in a poster session at the meeting.

Significant benefit was seen on the limb and bulbar subscales, and there was a trend favoring edaravone on the respiratory subscale. Additionally, patients given edaravone had comparatively less deterioration in quality of life as assessed with the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) (P = .03). Grip strength did not differ between groups, and there were no deaths in either group.

“We are not aware of any other positive phase III study in maybe a generation, since riluzole, in ALS. So we are showing this data and we are hopeful that people are as excited as we are,” Dr. Palumbo said in an interview.

In the area of safety, edaravone and placebo did not differ significantly with respect to the rate of adverse events, with contusion, dysphagia, and constipation predominating. The most common serious adverse event was dysphagia, seen in 12% of each group.

The trial’s findings led to approval of edaravone for treatment of ALS in Japan, where it is marketed as Radicut. Additionally, the U.S. Food and Drug Administration (FDA) granted edaravone orphan drug designation for ALS but has not approved it for this indication.

An additional 24-week open-label extension study among 123 patients from the trial, in which all received the drug regardless of their initially assigned treatment, showed that the benefit of edaravone was durable. Patients who continued treatment with the drug had less of a decline from baseline in ALSFRS-R score than did peers switched to the drug from placebo (difference between groups, 4.17; P = .004), according to data reported in another poster. Also, the former had a lower risk of death (P = .019) and less decline in lung function. Meanwhile, the drug’s safety profile remained good.

The researchers are preparing their findings for journal submission and are revisiting the drug’s regulatory status in the United States, according to Dr. Palumbo. “We’re talking to the FDA now. We’ve got our fingers crossed.”

There is no compelling reason to think that the drug’s efficacy in the U.S. population would differ from that in the Japanese population, but that will ultimately be an issue for regulators to decide, he said.

It is difficult to compare edaravone with other ALS treatment options, as all patients in the trial concomitantly received standard of care, Dr. Palumbo explained. “We can only speak about standard of care, and we think that we’ve improved on standard of care here,” he maintained.

The initial phase III trial of edaravone in ALS, which enrolled a population having a wider range of disease severity, failed to meet its primary endpoint of improvement in ALSFRS-R score (Amyotroph Lateral Scler Frontotemporal Degener. 2014;15:610-7). An extension study in 181 patients, also reported in a poster at the meeting, supported post hoc findings hinting that the timing of drug initiation was important.

“We learned a tremendous amount in that study about who the patients were who would ultimately benefit,” Dr. Palumbo commented. “We had a number of hypotheses. One hypothesis was that if we found patients who in fact were still functional at baseline and who really had the diagnosis – they had either definite or probable ALS – and still had very good respiratory function, that we would likely find a signal there.”

Rounding out the set of trials was a small randomized placebo-controlled trial among 25 patients with more advanced ALS, done at the request of Japanese health authorities. Results showed that edaravone was safe in this population but had no clear benefit.

Dr. Palumbo disclosed that he is an employee of Mitsubishi Tanabe Pharma Development America, Inc. The trials were sponsored by Mitsubishi Tanabe Pharma Corporation.

VANCOUVER – Dimethyl fumarate and fingolimod appear to have an edge over other disease-modifying therapies for multiple sclerosis (MS) in real-world practice, according to a comparative effectiveness study reported at the annual meeting of the American Academy of Neurology.

Dr. Jacqueline A. Nicholas, a neuroimmunologist and MS specialist with the OhioHealth Multiple Sclerosis Center, Riverside Methodist Hospital, Columbus, and her colleagues analyzed claims data from 5,004 commercially insured adults with MS in the United States who started treatment with any of five oral and injectable disease-modifying therapies.

Susan London/Frontline Medical News

Findings reported at the meeting showed that dimethyl fumarate netted the greatest reduction in annualized relapse rate, at one-third, followed by fingolimod, at about one-fourth. The adjusted risk of relapse in the year after drug initiation was significantly higher for interferon-beta, glatiramer acetate, and teriflunomide, compared with dimethyl fumarate.

“Right now, a lot of the data that we have to use in the clinic is based on clinical trials data. That’s often not what we see in the real world, the MS centers, and even the outpatient neurology setting,” Dr. Nicholas said in an interview. “This study is nice just because it points out that when you look at real-world data, it shows, yes, that these drugs work, and that some of the initial benefit for the oral disease-modifying therapies is what we thought. Obviously, we don’t have cross-trial comparisons to make from the clinical trials, so this is real data that we can actually use in our clinic setting.”

The findings are also helpful given changing health care models and ongoing issues with reimbursement and obtaining insurance approval to use various drugs, she added. “These are things that we can show to those payers as to why it’s important that we have these therapies and that we be able to decide as MS specialists what’s going to be best for the patient.

“Right now, the biggest challenge in the MS world is that obviously, as an MS specialist, you have a lot of experience and knowledge. And based on poor prognostic factors, when somebody comes in, you may not want to go with an escalation model [of treatment], where you are starting with something that a payer may think we should start with, an injectable,” Dr. Nicholas added. “Somebody may have more aggressive disease, and maybe you are going to want to start with an oral or an IV drug. But the payers are the ones right now who have the say. So it’s a lot of time and a lot of work [getting insurance approval], and while you are fighting to get what you know your patient needs, your patient’s suffering, accumulating disability, and possibly having more relapses.”

For the study, the investigators analyzed administrative data from the Truven MarketScan Commercial Claims Databases for 2012 through 2014.

Analyses were based on 2,564 patients treated with dimethyl fumarate (brand name Tecfidera), 735 with interferon-beta (Rebif, Avonex, Betaseron, and Extavia), 827 with glatiramer acetate (Copaxone), 417 with teriflunomide (Aubagio), and 461 with fingolimod (Gilenya).

Comparing the year before and the year after drug initiation, only dimethyl fumarate and fingolimod were associated with significant reductions in the annualized relapse rate, according to findings reported in a poster session. The reductions were 33% and 27%, respectively.

In the postinitiation year and with dimethyl fumarate as the comparator, the adjusted incidence rate ratio for relapse was similar for fingolimod but significantly higher for glatiramer acetate (1.28), interferon-beta (1.25), and teriflunomide (1.28).

“I don’t think that these findings are surprising,” Dr. Nicholas said. “I work in a large MS center and I would say this is generally what I see clinically in terms of the effectiveness. So it’s more reassuring to me than anything.”

She acknowledged that safety and tolerability will also come into play when selecting among disease-modifying therapies. “Those data are incredibly important, and we certainly balance that. With a health care claims database, that’s hard data to pull unless you are looking at one specific [adverse effect], but that’s something that needs to be very carefully weighed with the efficacy data for the patient,” she said.

In a companion study also reported in the poster session, the investigators compared the impact of starting the same five drugs on health care costs and utilization.

Results of that study showed that total health care costs rose in the postinitiation year for all five drugs, with the increase ranging from $38,801 for dimethyl fumarate to $52,352 for fingolimod.

However, total nonprescription medical costs decreased across the board, apparently driven by both less use of outpatient services and fewer inpatient hospital stays, with the greatest reduction seen for dimethyl fumarate.

Dr. Nicholas disclosed that she has received research funding from Genzyme, Novartis, Teva, Biogen, and Alexion, and has received consulting and speaking honoraria from Genzyme, Novartis, Teva, Biogen, and Medtronic. The study was supported by Biogen.

VANCOUVER – Dimethyl fumarate and fingolimod appear to have an edge over other disease-modifying therapies for multiple sclerosis (MS) in real-world practice, according to a comparative effectiveness study reported at the annual meeting of the American Academy of Neurology.

Dr. Jacqueline A. Nicholas, a neuroimmunologist and MS specialist with the OhioHealth Multiple Sclerosis Center, Riverside Methodist Hospital, Columbus, and her colleagues analyzed claims data from 5,004 commercially insured adults with MS in the United States who started treatment with any of five oral and injectable disease-modifying therapies.

Susan London/Frontline Medical News

Findings reported at the meeting showed that dimethyl fumarate netted the greatest reduction in annualized relapse rate, at one-third, followed by fingolimod, at about one-fourth. The adjusted risk of relapse in the year after drug initiation was significantly higher for interferon-beta, glatiramer acetate, and teriflunomide, compared with dimethyl fumarate.

“Right now, a lot of the data that we have to use in the clinic is based on clinical trials data. That’s often not what we see in the real world, the MS centers, and even the outpatient neurology setting,” Dr. Nicholas said in an interview. “This study is nice just because it points out that when you look at real-world data, it shows, yes, that these drugs work, and that some of the initial benefit for the oral disease-modifying therapies is what we thought. Obviously, we don’t have cross-trial comparisons to make from the clinical trials, so this is real data that we can actually use in our clinic setting.”

The findings are also helpful given changing health care models and ongoing issues with reimbursement and obtaining insurance approval to use various drugs, she added. “These are things that we can show to those payers as to why it’s important that we have these therapies and that we be able to decide as MS specialists what’s going to be best for the patient.

“Right now, the biggest challenge in the MS world is that obviously, as an MS specialist, you have a lot of experience and knowledge. And based on poor prognostic factors, when somebody comes in, you may not want to go with an escalation model [of treatment], where you are starting with something that a payer may think we should start with, an injectable,” Dr. Nicholas added. “Somebody may have more aggressive disease, and maybe you are going to want to start with an oral or an IV drug. But the payers are the ones right now who have the say. So it’s a lot of time and a lot of work [getting insurance approval], and while you are fighting to get what you know your patient needs, your patient’s suffering, accumulating disability, and possibly having more relapses.”

For the study, the investigators analyzed administrative data from the Truven MarketScan Commercial Claims Databases for 2012 through 2014.

Analyses were based on 2,564 patients treated with dimethyl fumarate (brand name Tecfidera), 735 with interferon-beta (Rebif, Avonex, Betaseron, and Extavia), 827 with glatiramer acetate (Copaxone), 417 with teriflunomide (Aubagio), and 461 with fingolimod (Gilenya).

Comparing the year before and the year after drug initiation, only dimethyl fumarate and fingolimod were associated with significant reductions in the annualized relapse rate, according to findings reported in a poster session. The reductions were 33% and 27%, respectively.

In the postinitiation year and with dimethyl fumarate as the comparator, the adjusted incidence rate ratio for relapse was similar for fingolimod but significantly higher for glatiramer acetate (1.28), interferon-beta (1.25), and teriflunomide (1.28).

“I don’t think that these findings are surprising,” Dr. Nicholas said. “I work in a large MS center and I would say this is generally what I see clinically in terms of the effectiveness. So it’s more reassuring to me than anything.”

She acknowledged that safety and tolerability will also come into play when selecting among disease-modifying therapies. “Those data are incredibly important, and we certainly balance that. With a health care claims database, that’s hard data to pull unless you are looking at one specific [adverse effect], but that’s something that needs to be very carefully weighed with the efficacy data for the patient,” she said.

In a companion study also reported in the poster session, the investigators compared the impact of starting the same five drugs on health care costs and utilization.

Results of that study showed that total health care costs rose in the postinitiation year for all five drugs, with the increase ranging from $38,801 for dimethyl fumarate to $52,352 for fingolimod.

However, total nonprescription medical costs decreased across the board, apparently driven by both less use of outpatient services and fewer inpatient hospital stays, with the greatest reduction seen for dimethyl fumarate.

Dr. Nicholas disclosed that she has received research funding from Genzyme, Novartis, Teva, Biogen, and Alexion, and has received consulting and speaking honoraria from Genzyme, Novartis, Teva, Biogen, and Medtronic. The study was supported by Biogen.

VANCOUVER – Dimethyl fumarate and fingolimod appear to have an edge over other disease-modifying therapies for multiple sclerosis (MS) in real-world practice, according to a comparative effectiveness study reported at the annual meeting of the American Academy of Neurology.

Dr. Jacqueline A. Nicholas, a neuroimmunologist and MS specialist with the OhioHealth Multiple Sclerosis Center, Riverside Methodist Hospital, Columbus, and her colleagues analyzed claims data from 5,004 commercially insured adults with MS in the United States who started treatment with any of five oral and injectable disease-modifying therapies.

Susan London/Frontline Medical News

Findings reported at the meeting showed that dimethyl fumarate netted the greatest reduction in annualized relapse rate, at one-third, followed by fingolimod, at about one-fourth. The adjusted risk of relapse in the year after drug initiation was significantly higher for interferon-beta, glatiramer acetate, and teriflunomide, compared with dimethyl fumarate.

“Right now, a lot of the data that we have to use in the clinic is based on clinical trials data. That’s often not what we see in the real world, the MS centers, and even the outpatient neurology setting,” Dr. Nicholas said in an interview. “This study is nice just because it points out that when you look at real-world data, it shows, yes, that these drugs work, and that some of the initial benefit for the oral disease-modifying therapies is what we thought. Obviously, we don’t have cross-trial comparisons to make from the clinical trials, so this is real data that we can actually use in our clinic setting.”

The findings are also helpful given changing health care models and ongoing issues with reimbursement and obtaining insurance approval to use various drugs, she added. “These are things that we can show to those payers as to why it’s important that we have these therapies and that we be able to decide as MS specialists what’s going to be best for the patient.

“Right now, the biggest challenge in the MS world is that obviously, as an MS specialist, you have a lot of experience and knowledge. And based on poor prognostic factors, when somebody comes in, you may not want to go with an escalation model [of treatment], where you are starting with something that a payer may think we should start with, an injectable,” Dr. Nicholas added. “Somebody may have more aggressive disease, and maybe you are going to want to start with an oral or an IV drug. But the payers are the ones right now who have the say. So it’s a lot of time and a lot of work [getting insurance approval], and while you are fighting to get what you know your patient needs, your patient’s suffering, accumulating disability, and possibly having more relapses.”

For the study, the investigators analyzed administrative data from the Truven MarketScan Commercial Claims Databases for 2012 through 2014.

Analyses were based on 2,564 patients treated with dimethyl fumarate (brand name Tecfidera), 735 with interferon-beta (Rebif, Avonex, Betaseron, and Extavia), 827 with glatiramer acetate (Copaxone), 417 with teriflunomide (Aubagio), and 461 with fingolimod (Gilenya).

Comparing the year before and the year after drug initiation, only dimethyl fumarate and fingolimod were associated with significant reductions in the annualized relapse rate, according to findings reported in a poster session. The reductions were 33% and 27%, respectively.

In the postinitiation year and with dimethyl fumarate as the comparator, the adjusted incidence rate ratio for relapse was similar for fingolimod but significantly higher for glatiramer acetate (1.28), interferon-beta (1.25), and teriflunomide (1.28).

“I don’t think that these findings are surprising,” Dr. Nicholas said. “I work in a large MS center and I would say this is generally what I see clinically in terms of the effectiveness. So it’s more reassuring to me than anything.”

She acknowledged that safety and tolerability will also come into play when selecting among disease-modifying therapies. “Those data are incredibly important, and we certainly balance that. With a health care claims database, that’s hard data to pull unless you are looking at one specific [adverse effect], but that’s something that needs to be very carefully weighed with the efficacy data for the patient,” she said.

In a companion study also reported in the poster session, the investigators compared the impact of starting the same five drugs on health care costs and utilization.

Results of that study showed that total health care costs rose in the postinitiation year for all five drugs, with the increase ranging from $38,801 for dimethyl fumarate to $52,352 for fingolimod.

However, total nonprescription medical costs decreased across the board, apparently driven by both less use of outpatient services and fewer inpatient hospital stays, with the greatest reduction seen for dimethyl fumarate.

Dr. Nicholas disclosed that she has received research funding from Genzyme, Novartis, Teva, Biogen, and Alexion, and has received consulting and speaking honoraria from Genzyme, Novartis, Teva, Biogen, and Medtronic. The study was supported by Biogen.

CHICAGO – The immune checkpoint inhibitor atezolizumab is efficacious when used as first-line therapy for advanced urothelial carcinoma, according to a study reported at the annual meeting of the American Society of Clinical Oncology.

The study – cohort 1 of the IMvigor210 trial – was conducted among 119 cisplatin-ineligible patients with metastatic or locally advanced disease. All were treated with the antibody atezolizumab, which targets PD-L1 (programmed death–ligand 1), a negative regulator of the immune system, and thereby promotes the antitumor immune response.

Nearly a quarter of patients had a tumor response to atezolizumab, and median overall survival approached 15 months, first author Dr. Arjun V. Balar of the New York University Langone Medical Center and director of genitourinary medical oncology at the NYU Perlmutter Cancer Center, New York, reported in a session and press briefing.

“Overall, this therapy was efficacious and also very well tolerated,” he commented. “These data make a compelling argument for atezolizumab to be a potential new standard of care in patients with cisplatin-ineligible metastatic urothelial cancer. However, moreover, they could represent the beginning of a seismic shift in our treatment approach to all patients with metastatic disease, irrespective of their eligibility for cisplatin.”

Positive findings from the trial’s cohort 2, patients who had already received platinum-based chemotherapy for advanced disease, recently led to the agent’s approval by the Food and Drug Administration for use in that population.

Cohort 1 was initially set up as an exploratory study but was expanded, Dr. Balar explained. “I do think that there is a benefit there, but until we have comparative data, it’s going to be really hard to hold that against immunotherapy necessarily,” he acknowledged. “That being said, do I envision a future where there is PD-L1 and PD-1 targeted therapy as a front-line therapy? Yes, absolutely, I think we are headed in that direction. We just need the trials to show it.”

ASCO expert Dr. Charles Ryan, professor of clinical medicine and urology program leader, genitourinary medical oncology, at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, concurred, saying, “I think it is safe at this point to envision a future where PD-L1 therapy could be used in the front line, but we do need to do those confirmatory studies.

“I would just underscore that in this study, the importance is that this is cisplatin ineligible as opposed to carboplatin treated,” Dr. Ryan added. “Cisplatin is the only platinum in bladder cancer that is associated with a survival benefit, so this is a very significant point to make. A very substantial part of the bladder cancer population, many patients out there, are cisplatin ineligible due to a variety of reasons, because organ dysfunction is quite common in advanced urothelial cancer.”

Patients were entered into IMVigor210’s cohort 1 if they had impaired kidney function, peripheral neuropathy, moderate to severe hearing loss, or poor performance status, precluding the use of cisplatin.

All were treated with atezolizumab (Tecentriq) every 3 weeks until investigator-defined progression. To evaluate a potential biomarker for benefit, the investigators assessed PD-L1 expression on tumor-infiltrating immune cells by immunohistochemistry in archival tissue.

Study results showed that with a median follow-up of 14.4 months, the centrally confirmed overall response rate, the study’s primary endpoint, was 24% (7% of patients had a complete response and 17% had a partial response), Dr. Balar reported.

Complete responses were seen in all subgroups of patients stratified by PD-L1 expression. Fully 75% of all responses were still ongoing at the time of data cutoff, and the median duration of response has not yet been reached in any of the subgroups.

The median duration of overall survival was 14.8 months, and the 1-year rate of overall survival was 57%, although data for that endpoint are still immature. Survival also appeared to be similar regardless of PD-L1 expression.

Taken together, these efficacy findings compare favorably with those seen historically in similar patients treated with other agents in trials and in real-world settings, according to Dr. Balar.

Atezolizumab was well tolerated, with only 6% of patients experiencing an adverse event leading to trial discontinuation. Most events seen were of grade 1 or 2 severity; a single patient had a grade 5 event (sepsis).

About 15% of patients had treatment-related grade 3 or 4 adverse events, about the same as the rate seen in cohort 2. The most common were fatigue and an increase in liver enzymes.

Overall, 14% of patients had an immune-mediated adverse event requiring corticosteroid treatment. “Notably, no patients required any other immunosuppression beyond steroids for the management of an immune-related adverse event,” he reported

The PD-L1 analyses in the trial had some limitations, Dr. Balar said. “PD-L1 testing continues to be the most hotly contested issue,” he said. “Obviously, the immune system is very dynamic, and we were testing something in archival specimens, in a static environment, so there are obviously all the caveats there.”

Some data have suggested that mutational burden may help identify the patient subset who will benefit. However, “to be able to make your decision in the clinic, those types of readouts need to be timely …, and I think that’s the gap,” he commented. “So in the future, is the right biomarker PD-1 or PD-L1? My hunch is no, that is probably not the right biomarker, there are probably better ones, and those are being worked on.”

Dr. Balar disclosed that he has a consulting or advisory role with Cerulean Pharma, Dendreon, Pfizer, and Roche/Genentech. The trial was sponsored by Hoffmann-La Roche. Ventana Medical Systems assisted with PD-L1 testing.

CHICAGO – The immune checkpoint inhibitor atezolizumab is efficacious when used as first-line therapy for advanced urothelial carcinoma, according to a study reported at the annual meeting of the American Society of Clinical Oncology.

The study – cohort 1 of the IMvigor210 trial – was conducted among 119 cisplatin-ineligible patients with metastatic or locally advanced disease. All were treated with the antibody atezolizumab, which targets PD-L1 (programmed death–ligand 1), a negative regulator of the immune system, and thereby promotes the antitumor immune response.

Nearly a quarter of patients had a tumor response to atezolizumab, and median overall survival approached 15 months, first author Dr. Arjun V. Balar of the New York University Langone Medical Center and director of genitourinary medical oncology at the NYU Perlmutter Cancer Center, New York, reported in a session and press briefing.

“Overall, this therapy was efficacious and also very well tolerated,” he commented. “These data make a compelling argument for atezolizumab to be a potential new standard of care in patients with cisplatin-ineligible metastatic urothelial cancer. However, moreover, they could represent the beginning of a seismic shift in our treatment approach to all patients with metastatic disease, irrespective of their eligibility for cisplatin.”

Positive findings from the trial’s cohort 2, patients who had already received platinum-based chemotherapy for advanced disease, recently led to the agent’s approval by the Food and Drug Administration for use in that population.

Cohort 1 was initially set up as an exploratory study but was expanded, Dr. Balar explained. “I do think that there is a benefit there, but until we have comparative data, it’s going to be really hard to hold that against immunotherapy necessarily,” he acknowledged. “That being said, do I envision a future where there is PD-L1 and PD-1 targeted therapy as a front-line therapy? Yes, absolutely, I think we are headed in that direction. We just need the trials to show it.”

ASCO expert Dr. Charles Ryan, professor of clinical medicine and urology program leader, genitourinary medical oncology, at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, concurred, saying, “I think it is safe at this point to envision a future where PD-L1 therapy could be used in the front line, but we do need to do those confirmatory studies.

“I would just underscore that in this study, the importance is that this is cisplatin ineligible as opposed to carboplatin treated,” Dr. Ryan added. “Cisplatin is the only platinum in bladder cancer that is associated with a survival benefit, so this is a very significant point to make. A very substantial part of the bladder cancer population, many patients out there, are cisplatin ineligible due to a variety of reasons, because organ dysfunction is quite common in advanced urothelial cancer.”

Patients were entered into IMVigor210’s cohort 1 if they had impaired kidney function, peripheral neuropathy, moderate to severe hearing loss, or poor performance status, precluding the use of cisplatin.

All were treated with atezolizumab (Tecentriq) every 3 weeks until investigator-defined progression. To evaluate a potential biomarker for benefit, the investigators assessed PD-L1 expression on tumor-infiltrating immune cells by immunohistochemistry in archival tissue.

Study results showed that with a median follow-up of 14.4 months, the centrally confirmed overall response rate, the study’s primary endpoint, was 24% (7% of patients had a complete response and 17% had a partial response), Dr. Balar reported.

Complete responses were seen in all subgroups of patients stratified by PD-L1 expression. Fully 75% of all responses were still ongoing at the time of data cutoff, and the median duration of response has not yet been reached in any of the subgroups.

The median duration of overall survival was 14.8 months, and the 1-year rate of overall survival was 57%, although data for that endpoint are still immature. Survival also appeared to be similar regardless of PD-L1 expression.

Taken together, these efficacy findings compare favorably with those seen historically in similar patients treated with other agents in trials and in real-world settings, according to Dr. Balar.

Atezolizumab was well tolerated, with only 6% of patients experiencing an adverse event leading to trial discontinuation. Most events seen were of grade 1 or 2 severity; a single patient had a grade 5 event (sepsis).

About 15% of patients had treatment-related grade 3 or 4 adverse events, about the same as the rate seen in cohort 2. The most common were fatigue and an increase in liver enzymes.

Overall, 14% of patients had an immune-mediated adverse event requiring corticosteroid treatment. “Notably, no patients required any other immunosuppression beyond steroids for the management of an immune-related adverse event,” he reported

The PD-L1 analyses in the trial had some limitations, Dr. Balar said. “PD-L1 testing continues to be the most hotly contested issue,” he said. “Obviously, the immune system is very dynamic, and we were testing something in archival specimens, in a static environment, so there are obviously all the caveats there.”

Some data have suggested that mutational burden may help identify the patient subset who will benefit. However, “to be able to make your decision in the clinic, those types of readouts need to be timely …, and I think that’s the gap,” he commented. “So in the future, is the right biomarker PD-1 or PD-L1? My hunch is no, that is probably not the right biomarker, there are probably better ones, and those are being worked on.”

Dr. Balar disclosed that he has a consulting or advisory role with Cerulean Pharma, Dendreon, Pfizer, and Roche/Genentech. The trial was sponsored by Hoffmann-La Roche. Ventana Medical Systems assisted with PD-L1 testing.

CHICAGO – The immune checkpoint inhibitor atezolizumab is efficacious when used as first-line therapy for advanced urothelial carcinoma, according to a study reported at the annual meeting of the American Society of Clinical Oncology.

The study – cohort 1 of the IMvigor210 trial – was conducted among 119 cisplatin-ineligible patients with metastatic or locally advanced disease. All were treated with the antibody atezolizumab, which targets PD-L1 (programmed death–ligand 1), a negative regulator of the immune system, and thereby promotes the antitumor immune response.

Nearly a quarter of patients had a tumor response to atezolizumab, and median overall survival approached 15 months, first author Dr. Arjun V. Balar of the New York University Langone Medical Center and director of genitourinary medical oncology at the NYU Perlmutter Cancer Center, New York, reported in a session and press briefing.

“Overall, this therapy was efficacious and also very well tolerated,” he commented. “These data make a compelling argument for atezolizumab to be a potential new standard of care in patients with cisplatin-ineligible metastatic urothelial cancer. However, moreover, they could represent the beginning of a seismic shift in our treatment approach to all patients with metastatic disease, irrespective of their eligibility for cisplatin.”

Positive findings from the trial’s cohort 2, patients who had already received platinum-based chemotherapy for advanced disease, recently led to the agent’s approval by the Food and Drug Administration for use in that population.

Cohort 1 was initially set up as an exploratory study but was expanded, Dr. Balar explained. “I do think that there is a benefit there, but until we have comparative data, it’s going to be really hard to hold that against immunotherapy necessarily,” he acknowledged. “That being said, do I envision a future where there is PD-L1 and PD-1 targeted therapy as a front-line therapy? Yes, absolutely, I think we are headed in that direction. We just need the trials to show it.”

ASCO expert Dr. Charles Ryan, professor of clinical medicine and urology program leader, genitourinary medical oncology, at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, concurred, saying, “I think it is safe at this point to envision a future where PD-L1 therapy could be used in the front line, but we do need to do those confirmatory studies.

“I would just underscore that in this study, the importance is that this is cisplatin ineligible as opposed to carboplatin treated,” Dr. Ryan added. “Cisplatin is the only platinum in bladder cancer that is associated with a survival benefit, so this is a very significant point to make. A very substantial part of the bladder cancer population, many patients out there, are cisplatin ineligible due to a variety of reasons, because organ dysfunction is quite common in advanced urothelial cancer.”

Patients were entered into IMVigor210’s cohort 1 if they had impaired kidney function, peripheral neuropathy, moderate to severe hearing loss, or poor performance status, precluding the use of cisplatin.

All were treated with atezolizumab (Tecentriq) every 3 weeks until investigator-defined progression. To evaluate a potential biomarker for benefit, the investigators assessed PD-L1 expression on tumor-infiltrating immune cells by immunohistochemistry in archival tissue.

Study results showed that with a median follow-up of 14.4 months, the centrally confirmed overall response rate, the study’s primary endpoint, was 24% (7% of patients had a complete response and 17% had a partial response), Dr. Balar reported.

Complete responses were seen in all subgroups of patients stratified by PD-L1 expression. Fully 75% of all responses were still ongoing at the time of data cutoff, and the median duration of response has not yet been reached in any of the subgroups.

The median duration of overall survival was 14.8 months, and the 1-year rate of overall survival was 57%, although data for that endpoint are still immature. Survival also appeared to be similar regardless of PD-L1 expression.

Taken together, these efficacy findings compare favorably with those seen historically in similar patients treated with other agents in trials and in real-world settings, according to Dr. Balar.

Atezolizumab was well tolerated, with only 6% of patients experiencing an adverse event leading to trial discontinuation. Most events seen were of grade 1 or 2 severity; a single patient had a grade 5 event (sepsis).

About 15% of patients had treatment-related grade 3 or 4 adverse events, about the same as the rate seen in cohort 2. The most common were fatigue and an increase in liver enzymes.

Overall, 14% of patients had an immune-mediated adverse event requiring corticosteroid treatment. “Notably, no patients required any other immunosuppression beyond steroids for the management of an immune-related adverse event,” he reported

The PD-L1 analyses in the trial had some limitations, Dr. Balar said. “PD-L1 testing continues to be the most hotly contested issue,” he said. “Obviously, the immune system is very dynamic, and we were testing something in archival specimens, in a static environment, so there are obviously all the caveats there.”

Some data have suggested that mutational burden may help identify the patient subset who will benefit. However, “to be able to make your decision in the clinic, those types of readouts need to be timely …, and I think that’s the gap,” he commented. “So in the future, is the right biomarker PD-1 or PD-L1? My hunch is no, that is probably not the right biomarker, there are probably better ones, and those are being worked on.”

Dr. Balar disclosed that he has a consulting or advisory role with Cerulean Pharma, Dendreon, Pfizer, and Roche/Genentech. The trial was sponsored by Hoffmann-La Roche. Ventana Medical Systems assisted with PD-L1 testing.

CHICAGO – Extending adjuvant aromatase inhibitor (AI) therapy from 5 years to 10 years further reduces the risk of recurrence and new breast cancer in postmenopausal women treated for early disease, according to findings of the MA17.R trial.

In the phase III trial conducted by the Canadian Cancer Trials Group and the North American Breast Cancer Group, 1,918 postmenopausal women who had completed about 5 years of AI therapy (preceded by tamoxifen in the majority of cases) were randomized to take the AI letrozole or to stop therapy by taking placebo for an additional 5 years.

Compared with peers who stopped, women who continued AI therapy for 5 more years had a 34% lower risk of recurrence or contralateral breast cancer, investigators reported in sessions and a press briefing at the annual meeting of the American Society of Clinical Oncology. The trade-off was a small increase in the rates of skeletal adverse events such as fractures; quality of life was essentially unaffected.

“MA17.R is the first study to show the benefit of extending an adjuvant aromatase inhibitor beyond 5 years,” commented lead investigator Paul E. Goss, M.D., director of the Breast Cancer Research Program at the Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston. “Unlike many anticancer therapies, aromatase inhibitors are readily accessible around the world, and therefore, our results will further improve the outcome of many women with breast cancer.”

The disease-free survival curves will likely separate further, given a “legacy effect” of endocrine therapy that persists after it ends, he predicted. “And I think overall survival will eventually become positive in MA.17R. … The Food and Drug Administration has taken the opinion that overall survival follows disease-free survival like night follows day for endocrine therapies, and I think they are correct, I think that’s what we see in all the trials.”

Implications

It remains unclear how patients should be managed after 10 years of an AI, according to Dr. Goss. “That’s uncharted waters,” he elaborated. “We know from the curve of the natural history of this disease that it chronically relapses, and we continue to see patients 25 years after their primary diagnosis with a recurrence.” Some data in mice suggest there may be benefit from continuing the AI until recurrence. “I don’t think that would be entered into in clinical practice as a rule, because there is no clinical trial of that,” he said. “But this data will now take the aromatase inhibitors out to 10 years.”

The MA.17R trial’s findings show that extended duration of AI therapy is “clinically valuable,” according to ASCO expert Harold J. Burstein, M.D., Ph.D., a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at the Harvard Medical School in Boston. He predicted the findings will have at least two consequences.

“One is tremendous interest in longer durations of therapy with the AI, but also some tailoring of treatment based on how the patient has fared with their therapy and on their baseline risk of recurrence. So women who have less risky cancer will probably be less inclined to pursue these longer durations, and women who have higher-risk cancers will be more inclined,” he explained.

Also, “women who have finished 5 years of an AI without any prior tamoxifen I think are going to be very compelled by these data, whereas women who have had 5 years of tamoxifen, 5 years of an AI, and are already 10 years out probably get less benefit numerically from yet longer duration of therapy,” he added. “And we are certainly not at the point of saying that women should be on these drugs for the rest of their lives.”

MA.17R design

Postmenopausal women were eligible for MA.17R if they had undergone resection of hormone receptor–positive early breast cancer and had already completed about 5 years of therapy with any of the three AIs currently on the market. In the large majority of cases, they also had previously received tamoxifen.

Many of the women came from the parent MA.17 trial, which tested an initial 5 years of letrozole (brand name Femara) against placebo after tamoxifen therapy. Longer-term results of that trial, previously reported (J Clin Oncol. 2012;30:718-21), showed that this duration of letrozole had a significant disease-free survival benefit (hazard ratio, .52) and overall survival benefit (HR, .61).

In the MA.17R trial, the women were randomized to letrozole or a placebo for an additional 5 years, with a primary endpoint of disease-free survival and secondary endpoints including safety and quality of life.

Efficacy and safety

After a median follow-up of 6.3 years, the 5-year rate of disease-free survival was 95% with letrozole and 91% with placebo, according to results reported by Dr. Goss in a plenary session at the meeting and simultaneously published (N Engl J Med. 2016. June 5 doi: 10.1056/NEJMoa1604700).

The difference translated to a more than one-third reduction in the risk of disease recurrence or the occurrence of contralateral breast cancer (HR, .66; P = .01). Roughly three-fourths of recurrences were distant.

The groups did not differ significantly with respect to the rate of overall survival, which was 93% with letrozole and 94% with placebo.

The annual incidence of contralateral breast cancer was sharply lower in the letrozole group, at 0.21%, than in the placebo group, at 0.49%, translating to a more than one-half reduction in this risk of this outcome (HR, .42; P = .007).

No new toxicities or emergent symptoms were noted from extending AI therapy, according to Dr. Goss. However, the letrozole group significantly more commonly experienced bone pain (18% vs. 14%), bone fractures (14% vs. 9%), and new-onset osteoporosis (11% vs. 6%). Therefore, “bone health remains important for risk-benefit consideration,” he said.

Patient-reported outcomes

In a separate session and the press briefing, Dr. Julie Lemieux, a researcher at the Centre Hospitalier affilié Universitaire de Québec, reported the trial’s patient-reported outcomes, ascertained from questionnaires completed at baseline and annually out to 5 years.

In general, both the letrozole and placebo groups had small deteriorations over time in global quality of life as assessed from summary scores on the mental and physical scales of the 36-item Short Form Health Survey (SF-36). But both also had small improvements over time in scores on the Menopause-Specific Quality of Life (MENQOL) scale.

When compared, the two groups were statistically indistinguishable on most of these measures. The only significant difference was greater worsening in the letrozole group on the role function-physical subscale of the SF-36, which pertains to difficulty performing work or physical activity due to physical health. However, the difference averaged just 3.2 points, which fell short of the 5 points that the investigators considered clinically important.

“The limitation of this analysis was that it was a highly selected population. All of these women had already tolerated 5 years of an aromatase inhibitor, and about 70% had received 5 years of tamoxifen before,” Dr. Lemieux commented. “Also, they were clinical trial participants.”

Nonetheless, these findings “are very reassuring for those women who want a longer duration of adjuvant endocrine therapy that they can expect a preserved quality of life,” she concluded.

Dr. Goss disclosed that he had no relevant conflicts of interest. Dr. Lemieux disclosed that she had no relevant conflicts of interest. The trial received support from Novartis.

CHICAGO – Extending adjuvant aromatase inhibitor (AI) therapy from 5 years to 10 years further reduces the risk of recurrence and new breast cancer in postmenopausal women treated for early disease, according to findings of the MA17.R trial.

In the phase III trial conducted by the Canadian Cancer Trials Group and the North American Breast Cancer Group, 1,918 postmenopausal women who had completed about 5 years of AI therapy (preceded by tamoxifen in the majority of cases) were randomized to take the AI letrozole or to stop therapy by taking placebo for an additional 5 years.

Compared with peers who stopped, women who continued AI therapy for 5 more years had a 34% lower risk of recurrence or contralateral breast cancer, investigators reported in sessions and a press briefing at the annual meeting of the American Society of Clinical Oncology. The trade-off was a small increase in the rates of skeletal adverse events such as fractures; quality of life was essentially unaffected.

“MA17.R is the first study to show the benefit of extending an adjuvant aromatase inhibitor beyond 5 years,” commented lead investigator Paul E. Goss, M.D., director of the Breast Cancer Research Program at the Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston. “Unlike many anticancer therapies, aromatase inhibitors are readily accessible around the world, and therefore, our results will further improve the outcome of many women with breast cancer.”

The disease-free survival curves will likely separate further, given a “legacy effect” of endocrine therapy that persists after it ends, he predicted. “And I think overall survival will eventually become positive in MA.17R. … The Food and Drug Administration has taken the opinion that overall survival follows disease-free survival like night follows day for endocrine therapies, and I think they are correct, I think that’s what we see in all the trials.”

Implications

It remains unclear how patients should be managed after 10 years of an AI, according to Dr. Goss. “That’s uncharted waters,” he elaborated. “We know from the curve of the natural history of this disease that it chronically relapses, and we continue to see patients 25 years after their primary diagnosis with a recurrence.” Some data in mice suggest there may be benefit from continuing the AI until recurrence. “I don’t think that would be entered into in clinical practice as a rule, because there is no clinical trial of that,” he said. “But this data will now take the aromatase inhibitors out to 10 years.”

The MA.17R trial’s findings show that extended duration of AI therapy is “clinically valuable,” according to ASCO expert Harold J. Burstein, M.D., Ph.D., a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at the Harvard Medical School in Boston. He predicted the findings will have at least two consequences.

“One is tremendous interest in longer durations of therapy with the AI, but also some tailoring of treatment based on how the patient has fared with their therapy and on their baseline risk of recurrence. So women who have less risky cancer will probably be less inclined to pursue these longer durations, and women who have higher-risk cancers will be more inclined,” he explained.

Also, “women who have finished 5 years of an AI without any prior tamoxifen I think are going to be very compelled by these data, whereas women who have had 5 years of tamoxifen, 5 years of an AI, and are already 10 years out probably get less benefit numerically from yet longer duration of therapy,” he added. “And we are certainly not at the point of saying that women should be on these drugs for the rest of their lives.”

MA.17R design

Postmenopausal women were eligible for MA.17R if they had undergone resection of hormone receptor–positive early breast cancer and had already completed about 5 years of therapy with any of the three AIs currently on the market. In the large majority of cases, they also had previously received tamoxifen.

Many of the women came from the parent MA.17 trial, which tested an initial 5 years of letrozole (brand name Femara) against placebo after tamoxifen therapy. Longer-term results of that trial, previously reported (J Clin Oncol. 2012;30:718-21), showed that this duration of letrozole had a significant disease-free survival benefit (hazard ratio, .52) and overall survival benefit (HR, .61).

In the MA.17R trial, the women were randomized to letrozole or a placebo for an additional 5 years, with a primary endpoint of disease-free survival and secondary endpoints including safety and quality of life.

Efficacy and safety

After a median follow-up of 6.3 years, the 5-year rate of disease-free survival was 95% with letrozole and 91% with placebo, according to results reported by Dr. Goss in a plenary session at the meeting and simultaneously published (N Engl J Med. 2016. June 5 doi: 10.1056/NEJMoa1604700).

The difference translated to a more than one-third reduction in the risk of disease recurrence or the occurrence of contralateral breast cancer (HR, .66; P = .01). Roughly three-fourths of recurrences were distant.

The groups did not differ significantly with respect to the rate of overall survival, which was 93% with letrozole and 94% with placebo.

The annual incidence of contralateral breast cancer was sharply lower in the letrozole group, at 0.21%, than in the placebo group, at 0.49%, translating to a more than one-half reduction in this risk of this outcome (HR, .42; P = .007).

No new toxicities or emergent symptoms were noted from extending AI therapy, according to Dr. Goss. However, the letrozole group significantly more commonly experienced bone pain (18% vs. 14%), bone fractures (14% vs. 9%), and new-onset osteoporosis (11% vs. 6%). Therefore, “bone health remains important for risk-benefit consideration,” he said.

Patient-reported outcomes

In a separate session and the press briefing, Dr. Julie Lemieux, a researcher at the Centre Hospitalier affilié Universitaire de Québec, reported the trial’s patient-reported outcomes, ascertained from questionnaires completed at baseline and annually out to 5 years.

In general, both the letrozole and placebo groups had small deteriorations over time in global quality of life as assessed from summary scores on the mental and physical scales of the 36-item Short Form Health Survey (SF-36). But both also had small improvements over time in scores on the Menopause-Specific Quality of Life (MENQOL) scale.

When compared, the two groups were statistically indistinguishable on most of these measures. The only significant difference was greater worsening in the letrozole group on the role function-physical subscale of the SF-36, which pertains to difficulty performing work or physical activity due to physical health. However, the difference averaged just 3.2 points, which fell short of the 5 points that the investigators considered clinically important.

“The limitation of this analysis was that it was a highly selected population. All of these women had already tolerated 5 years of an aromatase inhibitor, and about 70% had received 5 years of tamoxifen before,” Dr. Lemieux commented. “Also, they were clinical trial participants.”

Nonetheless, these findings “are very reassuring for those women who want a longer duration of adjuvant endocrine therapy that they can expect a preserved quality of life,” she concluded.

Dr. Goss disclosed that he had no relevant conflicts of interest. Dr. Lemieux disclosed that she had no relevant conflicts of interest. The trial received support from Novartis.

CHICAGO – Extending adjuvant aromatase inhibitor (AI) therapy from 5 years to 10 years further reduces the risk of recurrence and new breast cancer in postmenopausal women treated for early disease, according to findings of the MA17.R trial.

In the phase III trial conducted by the Canadian Cancer Trials Group and the North American Breast Cancer Group, 1,918 postmenopausal women who had completed about 5 years of AI therapy (preceded by tamoxifen in the majority of cases) were randomized to take the AI letrozole or to stop therapy by taking placebo for an additional 5 years.

Compared with peers who stopped, women who continued AI therapy for 5 more years had a 34% lower risk of recurrence or contralateral breast cancer, investigators reported in sessions and a press briefing at the annual meeting of the American Society of Clinical Oncology. The trade-off was a small increase in the rates of skeletal adverse events such as fractures; quality of life was essentially unaffected.

“MA17.R is the first study to show the benefit of extending an adjuvant aromatase inhibitor beyond 5 years,” commented lead investigator Paul E. Goss, M.D., director of the Breast Cancer Research Program at the Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston. “Unlike many anticancer therapies, aromatase inhibitors are readily accessible around the world, and therefore, our results will further improve the outcome of many women with breast cancer.”

The disease-free survival curves will likely separate further, given a “legacy effect” of endocrine therapy that persists after it ends, he predicted. “And I think overall survival will eventually become positive in MA.17R. … The Food and Drug Administration has taken the opinion that overall survival follows disease-free survival like night follows day for endocrine therapies, and I think they are correct, I think that’s what we see in all the trials.”

Implications

It remains unclear how patients should be managed after 10 years of an AI, according to Dr. Goss. “That’s uncharted waters,” he elaborated. “We know from the curve of the natural history of this disease that it chronically relapses, and we continue to see patients 25 years after their primary diagnosis with a recurrence.” Some data in mice suggest there may be benefit from continuing the AI until recurrence. “I don’t think that would be entered into in clinical practice as a rule, because there is no clinical trial of that,” he said. “But this data will now take the aromatase inhibitors out to 10 years.”

The MA.17R trial’s findings show that extended duration of AI therapy is “clinically valuable,” according to ASCO expert Harold J. Burstein, M.D., Ph.D., a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at the Harvard Medical School in Boston. He predicted the findings will have at least two consequences.

“One is tremendous interest in longer durations of therapy with the AI, but also some tailoring of treatment based on how the patient has fared with their therapy and on their baseline risk of recurrence. So women who have less risky cancer will probably be less inclined to pursue these longer durations, and women who have higher-risk cancers will be more inclined,” he explained.

Also, “women who have finished 5 years of an AI without any prior tamoxifen I think are going to be very compelled by these data, whereas women who have had 5 years of tamoxifen, 5 years of an AI, and are already 10 years out probably get less benefit numerically from yet longer duration of therapy,” he added. “And we are certainly not at the point of saying that women should be on these drugs for the rest of their lives.”

MA.17R design

Postmenopausal women were eligible for MA.17R if they had undergone resection of hormone receptor–positive early breast cancer and had already completed about 5 years of therapy with any of the three AIs currently on the market. In the large majority of cases, they also had previously received tamoxifen.

Many of the women came from the parent MA.17 trial, which tested an initial 5 years of letrozole (brand name Femara) against placebo after tamoxifen therapy. Longer-term results of that trial, previously reported (J Clin Oncol. 2012;30:718-21), showed that this duration of letrozole had a significant disease-free survival benefit (hazard ratio, .52) and overall survival benefit (HR, .61).

In the MA.17R trial, the women were randomized to letrozole or a placebo for an additional 5 years, with a primary endpoint of disease-free survival and secondary endpoints including safety and quality of life.

Efficacy and safety

After a median follow-up of 6.3 years, the 5-year rate of disease-free survival was 95% with letrozole and 91% with placebo, according to results reported by Dr. Goss in a plenary session at the meeting and simultaneously published (N Engl J Med. 2016. June 5 doi: 10.1056/NEJMoa1604700).

The difference translated to a more than one-third reduction in the risk of disease recurrence or the occurrence of contralateral breast cancer (HR, .66; P = .01). Roughly three-fourths of recurrences were distant.

The groups did not differ significantly with respect to the rate of overall survival, which was 93% with letrozole and 94% with placebo.

The annual incidence of contralateral breast cancer was sharply lower in the letrozole group, at 0.21%, than in the placebo group, at 0.49%, translating to a more than one-half reduction in this risk of this outcome (HR, .42; P = .007).

No new toxicities or emergent symptoms were noted from extending AI therapy, according to Dr. Goss. However, the letrozole group significantly more commonly experienced bone pain (18% vs. 14%), bone fractures (14% vs. 9%), and new-onset osteoporosis (11% vs. 6%). Therefore, “bone health remains important for risk-benefit consideration,” he said.

Patient-reported outcomes

In a separate session and the press briefing, Dr. Julie Lemieux, a researcher at the Centre Hospitalier affilié Universitaire de Québec, reported the trial’s patient-reported outcomes, ascertained from questionnaires completed at baseline and annually out to 5 years.

In general, both the letrozole and placebo groups had small deteriorations over time in global quality of life as assessed from summary scores on the mental and physical scales of the 36-item Short Form Health Survey (SF-36). But both also had small improvements over time in scores on the Menopause-Specific Quality of Life (MENQOL) scale.

When compared, the two groups were statistically indistinguishable on most of these measures. The only significant difference was greater worsening in the letrozole group on the role function-physical subscale of the SF-36, which pertains to difficulty performing work or physical activity due to physical health. However, the difference averaged just 3.2 points, which fell short of the 5 points that the investigators considered clinically important.

“The limitation of this analysis was that it was a highly selected population. All of these women had already tolerated 5 years of an aromatase inhibitor, and about 70% had received 5 years of tamoxifen before,” Dr. Lemieux commented. “Also, they were clinical trial participants.”

Nonetheless, these findings “are very reassuring for those women who want a longer duration of adjuvant endocrine therapy that they can expect a preserved quality of life,” she concluded.

Dr. Goss disclosed that he had no relevant conflicts of interest. Dr. Lemieux disclosed that she had no relevant conflicts of interest. The trial received support from Novartis.

CHICAGO – Adding daratumumab to the current two-drug standard of care for relapsed or refractory multiple myeloma dramatically improves outcomes, according to results of an interim analysis of the phase III CASTOR trial.

When added to bortezomib and dexamethasone, the anti-CD38 antibody, which has both direct and indirect antimyeloma activity, reduced the risk of progression or death by 61%, with little increase in toxicity, investigators reported in a plenary session and press briefing at the annual meeting of the American Society of Clinical Oncology.

This magnitude of benefit is “unprecedented in randomized studies that compare novel treatments for relapsed, refractory multiple myeloma,” contended lead investigator Dr. Antonio Palumbo, chief of the multiple myeloma unit at the University of Torino, Italy.

“We hope this [daratumumab combination for myeloma] will be the translation of R-CHOP for lymphoma,” he added, referring to the addition of rituximab to an established backbone regimen. “Daratumumab-DVd [bortezomib-dexamethasone] might be considered today a new standard of care for relapsed and refractory multiple myeloma.”

At present, daratumumab is approved by the Food and Drug Administration for use only after patients have received at least three other therapies, Dr. Palumbo said.

“This study will open the opportunity to have a combination approach after diagnosis, therefore, at first relapse,” he commented, while noting that sufficient evidence should be obtained before using a drug for a new indication. “It’s very important to move as fast as we can this combination into the early phases of disease, where there is the major impact, even from a cost-efficacy point of view.”

The CASTOR findings add to evidence suggesting that daratumumab is synergistic with other myeloma therapies, according to invited discussant Dr. Paul G. Richardson, the R.J. Corman Professor of Medicine, Harvard Medical School, Boston, and the clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston.

“What I think is particularly impressive is the effect on the one-prior-line-of-treatment stratum,” he said, where the reduction in risk of progression or death was 69% with the addition of daratumumab.

Findings from the POLLUX trial, soon to be presented at another meeting, show a similar benefit when daratumumab is added to lenalidomide and dexamethasone in this setting, yielding a 63% reduction in the risk of events, according to Dr. Richardson. Additionally, other anti-CD38 antibodies and immune checkpoint inhibitors are being studied in this disease.

“I would first and foremost emphasize that this is not a zero-sum game. We need all of these drugs and all of these combinations to fight this disease,” he maintained, reviewing the many options now available. “But truly, the advent of the monoclonal antibody platform in this setting has resulted in hazard ratios that are unprecedented,” he agreed.

In CASTOR, 498 patients were randomized evenly to eight cycles of bortezomib (Velcade) plus dexamethasone, either alone or with the addition of daratumumab (Darzalex) given concurrently and then as monotherapy after completion of those cycles.

In the interim analysis, conducted at a median follow-up of about 7 months, the trial met its primary endpoint of progression-free survival: the median time to an event had not been reached with the daratumumab three-drug therapy but was 7.2 months with the standard two-drug therapy (hazard ratio, 0.39; P less than .0001). The difference translated to a more than doubling of the 1-year rate of progression-free survival (60.7% vs. 26.9%).

Benefit was generally consistent across patient subgroups stratified by disease characteristics and previous treatments, although greater impact was seen among the subgroups having earlier-stage or less heavily pretreated disease.

On the basis of these interim findings, patients in the standard therapy arm were allowed to cross over to get daratumumab, according to Dr. Palumbo.

The triple regimen was also associated with a higher overall response rate (83% vs. 63%; P less than .0001) as well as deeper responses, with a doubling in rates of both very good partial response (VGPR) or better and complete response (CR) or better.

“More patients do achieve a profound cytoreduction,” Dr. Palumbo said. “The remission duration is almost [tripled] in patients with a CR or VGPR versus patients with a minimal response or partial response.”

Data for overall survival are not yet mature, but at the time of the analysis, there was also a trend toward fewer deaths with daratumumab than without it (hazard ratio, 0.77).

“Daratumumab did not significantly increase any toxicity that was already present with the combination of bortezomib and dexamethasone,” Dr. Palumbo reported.

The three-drug regimen yielded somewhat higher rates of treatment-emergent thrombocytopenia (59% vs. 44%) and sensory peripheral neuropathy (47% vs. 38%). However, “this was mainly due to the fact that the experimental arm was longer exposed to bortezomib in comparison to the control arm that had a higher proportion of early progressions,” he explained. Additionally, the increase in thrombocytopenia did not translate into increased bleeding.

Forty-five percent of patients in the daratumumab arm had an infusion-related reaction, but nearly all reactions were limited to the first infusion.

The rate of discontinuation because of treatment-emergent adverse events was 7% with daratumumab and 9% without it.

Dr. Palumbo disclosed that he has a consulting or advisory role with and receives honoraria and research funding (institutional) from Genmab, Janssen-Cilag, and Takeda. The trial was sponsored by Janssen Research & Development.

CHICAGO – Adding daratumumab to the current two-drug standard of care for relapsed or refractory multiple myeloma dramatically improves outcomes, according to results of an interim analysis of the phase III CASTOR trial.

When added to bortezomib and dexamethasone, the anti-CD38 antibody, which has both direct and indirect antimyeloma activity, reduced the risk of progression or death by 61%, with little increase in toxicity, investigators reported in a plenary session and press briefing at the annual meeting of the American Society of Clinical Oncology.

This magnitude of benefit is “unprecedented in randomized studies that compare novel treatments for relapsed, refractory multiple myeloma,” contended lead investigator Dr. Antonio Palumbo, chief of the multiple myeloma unit at the University of Torino, Italy.

“We hope this [daratumumab combination for myeloma] will be the translation of R-CHOP for lymphoma,” he added, referring to the addition of rituximab to an established backbone regimen. “Daratumumab-DVd [bortezomib-dexamethasone] might be considered today a new standard of care for relapsed and refractory multiple myeloma.”

At present, daratumumab is approved by the Food and Drug Administration for use only after patients have received at least three other therapies, Dr. Palumbo said.

“This study will open the opportunity to have a combination approach after diagnosis, therefore, at first relapse,” he commented, while noting that sufficient evidence should be obtained before using a drug for a new indication. “It’s very important to move as fast as we can this combination into the early phases of disease, where there is the major impact, even from a cost-efficacy point of view.”

The CASTOR findings add to evidence suggesting that daratumumab is synergistic with other myeloma therapies, according to invited discussant Dr. Paul G. Richardson, the R.J. Corman Professor of Medicine, Harvard Medical School, Boston, and the clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston.

“What I think is particularly impressive is the effect on the one-prior-line-of-treatment stratum,” he said, where the reduction in risk of progression or death was 69% with the addition of daratumumab.

Findings from the POLLUX trial, soon to be presented at another meeting, show a similar benefit when daratumumab is added to lenalidomide and dexamethasone in this setting, yielding a 63% reduction in the risk of events, according to Dr. Richardson. Additionally, other anti-CD38 antibodies and immune checkpoint inhibitors are being studied in this disease.

“I would first and foremost emphasize that this is not a zero-sum game. We need all of these drugs and all of these combinations to fight this disease,” he maintained, reviewing the many options now available. “But truly, the advent of the monoclonal antibody platform in this setting has resulted in hazard ratios that are unprecedented,” he agreed.

In CASTOR, 498 patients were randomized evenly to eight cycles of bortezomib (Velcade) plus dexamethasone, either alone or with the addition of daratumumab (Darzalex) given concurrently and then as monotherapy after completion of those cycles.

In the interim analysis, conducted at a median follow-up of about 7 months, the trial met its primary endpoint of progression-free survival: the median time to an event had not been reached with the daratumumab three-drug therapy but was 7.2 months with the standard two-drug therapy (hazard ratio, 0.39; P less than .0001). The difference translated to a more than doubling of the 1-year rate of progression-free survival (60.7% vs. 26.9%).

Benefit was generally consistent across patient subgroups stratified by disease characteristics and previous treatments, although greater impact was seen among the subgroups having earlier-stage or less heavily pretreated disease.

On the basis of these interim findings, patients in the standard therapy arm were allowed to cross over to get daratumumab, according to Dr. Palumbo.

The triple regimen was also associated with a higher overall response rate (83% vs. 63%; P less than .0001) as well as deeper responses, with a doubling in rates of both very good partial response (VGPR) or better and complete response (CR) or better.

“More patients do achieve a profound cytoreduction,” Dr. Palumbo said. “The remission duration is almost [tripled] in patients with a CR or VGPR versus patients with a minimal response or partial response.”

Data for overall survival are not yet mature, but at the time of the analysis, there was also a trend toward fewer deaths with daratumumab than without it (hazard ratio, 0.77).

“Daratumumab did not significantly increase any toxicity that was already present with the combination of bortezomib and dexamethasone,” Dr. Palumbo reported.

The three-drug regimen yielded somewhat higher rates of treatment-emergent thrombocytopenia (59% vs. 44%) and sensory peripheral neuropathy (47% vs. 38%). However, “this was mainly due to the fact that the experimental arm was longer exposed to bortezomib in comparison to the control arm that had a higher proportion of early progressions,” he explained. Additionally, the increase in thrombocytopenia did not translate into increased bleeding.

Forty-five percent of patients in the daratumumab arm had an infusion-related reaction, but nearly all reactions were limited to the first infusion.

The rate of discontinuation because of treatment-emergent adverse events was 7% with daratumumab and 9% without it.

Dr. Palumbo disclosed that he has a consulting or advisory role with and receives honoraria and research funding (institutional) from Genmab, Janssen-Cilag, and Takeda. The trial was sponsored by Janssen Research & Development.

CHICAGO – Adding daratumumab to the current two-drug standard of care for relapsed or refractory multiple myeloma dramatically improves outcomes, according to results of an interim analysis of the phase III CASTOR trial.

When added to bortezomib and dexamethasone, the anti-CD38 antibody, which has both direct and indirect antimyeloma activity, reduced the risk of progression or death by 61%, with little increase in toxicity, investigators reported in a plenary session and press briefing at the annual meeting of the American Society of Clinical Oncology.

This magnitude of benefit is “unprecedented in randomized studies that compare novel treatments for relapsed, refractory multiple myeloma,” contended lead investigator Dr. Antonio Palumbo, chief of the multiple myeloma unit at the University of Torino, Italy.

“We hope this [daratumumab combination for myeloma] will be the translation of R-CHOP for lymphoma,” he added, referring to the addition of rituximab to an established backbone regimen. “Daratumumab-DVd [bortezomib-dexamethasone] might be considered today a new standard of care for relapsed and refractory multiple myeloma.”

At present, daratumumab is approved by the Food and Drug Administration for use only after patients have received at least three other therapies, Dr. Palumbo said.

“This study will open the opportunity to have a combination approach after diagnosis, therefore, at first relapse,” he commented, while noting that sufficient evidence should be obtained before using a drug for a new indication. “It’s very important to move as fast as we can this combination into the early phases of disease, where there is the major impact, even from a cost-efficacy point of view.”

The CASTOR findings add to evidence suggesting that daratumumab is synergistic with other myeloma therapies, according to invited discussant Dr. Paul G. Richardson, the R.J. Corman Professor of Medicine, Harvard Medical School, Boston, and the clinical program leader and director of clinical research at the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston.

“What I think is particularly impressive is the effect on the one-prior-line-of-treatment stratum,” he said, where the reduction in risk of progression or death was 69% with the addition of daratumumab.

Findings from the POLLUX trial, soon to be presented at another meeting, show a similar benefit when daratumumab is added to lenalidomide and dexamethasone in this setting, yielding a 63% reduction in the risk of events, according to Dr. Richardson. Additionally, other anti-CD38 antibodies and immune checkpoint inhibitors are being studied in this disease.

“I would first and foremost emphasize that this is not a zero-sum game. We need all of these drugs and all of these combinations to fight this disease,” he maintained, reviewing the many options now available. “But truly, the advent of the monoclonal antibody platform in this setting has resulted in hazard ratios that are unprecedented,” he agreed.

In CASTOR, 498 patients were randomized evenly to eight cycles of bortezomib (Velcade) plus dexamethasone, either alone or with the addition of daratumumab (Darzalex) given concurrently and then as monotherapy after completion of those cycles.

In the interim analysis, conducted at a median follow-up of about 7 months, the trial met its primary endpoint of progression-free survival: the median time to an event had not been reached with the daratumumab three-drug therapy but was 7.2 months with the standard two-drug therapy (hazard ratio, 0.39; P less than .0001). The difference translated to a more than doubling of the 1-year rate of progression-free survival (60.7% vs. 26.9%).

Benefit was generally consistent across patient subgroups stratified by disease characteristics and previous treatments, although greater impact was seen among the subgroups having earlier-stage or less heavily pretreated disease.

On the basis of these interim findings, patients in the standard therapy arm were allowed to cross over to get daratumumab, according to Dr. Palumbo.

The triple regimen was also associated with a higher overall response rate (83% vs. 63%; P less than .0001) as well as deeper responses, with a doubling in rates of both very good partial response (VGPR) or better and complete response (CR) or better.

“More patients do achieve a profound cytoreduction,” Dr. Palumbo said. “The remission duration is almost [tripled] in patients with a CR or VGPR versus patients with a minimal response or partial response.”

Data for overall survival are not yet mature, but at the time of the analysis, there was also a trend toward fewer deaths with daratumumab than without it (hazard ratio, 0.77).

“Daratumumab did not significantly increase any toxicity that was already present with the combination of bortezomib and dexamethasone,” Dr. Palumbo reported.

The three-drug regimen yielded somewhat higher rates of treatment-emergent thrombocytopenia (59% vs. 44%) and sensory peripheral neuropathy (47% vs. 38%). However, “this was mainly due to the fact that the experimental arm was longer exposed to bortezomib in comparison to the control arm that had a higher proportion of early progressions,” he explained. Additionally, the increase in thrombocytopenia did not translate into increased bleeding.

Forty-five percent of patients in the daratumumab arm had an infusion-related reaction, but nearly all reactions were limited to the first infusion.

The rate of discontinuation because of treatment-emergent adverse events was 7% with daratumumab and 9% without it.

Dr. Palumbo disclosed that he has a consulting or advisory role with and receives honoraria and research funding (institutional) from Genmab, Janssen-Cilag, and Takeda. The trial was sponsored by Janssen Research & Development.

SAN FRANCISCO – Mechanically ventilated patients in the intensive care unit (ICU) have poorer outcomes if extubated during the night instead of during the day, finds a retrospective cohort study reported at an international conference of the American Thoracic Society.

Overall, 20.1% of the nearly 98,000 adult patients studied were extubated during nighttime hours, between 7:00 p.m. and 7:00 a.m., according to data presented in a session and a related press conference.

Compared with patients extubated during daytime hours, patients extubated during nighttime hours had higher rates of ICU and hospital death, with the absolute difference ranging from 1.0% to 5.1%. Additionally, among those mechanically ventilated for at least 12 hours, nighttime extubation was associated with an absolute 2% increase in the risk of reintubation.

“I think this is the first large-scale study that looks at a practice that, although not as common as we thought it was, is still done about a fifth of the time and even with decreasing rates, is not a rare practice on our units,” commented lead author Dr. Hayley B. Gershengorn of the department of medicine (critical care) and the Saul R. Korey department of neurology at the Albert Einstein College of Medicine, New York.

“As we have increasing staffing [overnight] and maybe an increasing push to move people through our ICUs, we need to probably take some care because although we can’t demonstrate a causal link, it is quite concerning, this consistent finding of increased mortality and reintubation in these folks,” she said.

There are several possible reasons for the observed heightened risks of death and reintubation with nighttime extubation that could not be fully explored in the study, Dr. Gershengorn said.

“We were not able to identify the indication for extubation or discontinuation of mechanical ventilation. So one of the concerns that we have is that it’s probably more common that folks unintentionally extubate themselves or someone unintentionally extubates them overnight, when staffing is less,” she explained. “The other part, which we tried to adjust for but we don’t have perfect data on, is what is the staffing overnight,” including factors such as the ratio of nurses to patients and how many units an intensivist is covering, not just whether he or she is present.

“In terms of the reintubation risk being higher in the [group with longer duration of mechanical ventilation], the question I have is whether or not there is less comfort with somebody looking less well when there is less staff around, and whether or not there may be a quicker trigger to reintubate them if they don’t look so great,” she said.

The majority of intubated patients are unlikely to improve enough physiologically to prompt nighttime extubation rather than waiting until daytime, according to Dr. Gershengorn. But there are at least two groups whom clinicians might want to extubate at night.

One group is those who underwent elective surgery during the day. “They are waiting to come out of anesthesia, and the plan is to discontinue mechanical ventilation at the time that that occurs,” she explained. Another group is those who are agitated on the ventilator, require more sedation than usual, and suddenly awake at night. “These patients are really hard to keep comfortable. I can [sedate them] again and try this problem all over again tomorrow morning, or I can just bite the bullet and pull the tube out,” she said.

The investigators analyzed data from the Project IMPACT critical care medicine database, in which data are prospectively collected for benchmarking purposes. In all, they studied 97,844 mechanically ventilated adults from 165 medical and surgical ICUs across the United States between 2000 and 2009.

Results showed that nighttime extubation was more common among elective surgical patients, those coming from the operating room or a postanesthesia care unit, and those mechanically ventilated for less than 12 hours.

In a finding that Dr. Gershengorn described as surprising, there was a temporal trend by which the adjusted proportion of extubations performed at night actually decreased in more recent years during the study period.

The investigators next looked at outcomes among 10,279 propensity-matched pairs of patients, one member of the pair having been extubated during the night and the other having been extubated during the day.

Among those mechanically ventilated for less than 12 hours, nighttime extubation was associated with higher ICU mortality (5.6% vs. 4.6%; P = .025) and hospital mortality (8.3% vs. 7.0%; P = .014). Findings were inconsistent for length of stay, with nighttime extubation associated with a shorter ICU stay but a longer hospital stay.

Among patients mechanically ventilated for 12 hours or longer, those extubated during the night had a higher rate of reintubation (14.6% vs. 12.4%; P less than .001), as well as higher ICU mortality (11.2% vs. 6.1%; P less than .001) and hospital mortality (16.0% vs. 11.1%; P less than .001). Lengths of stay did not differ by extubation time of day in this group.

In sensitivity analyses, findings were similar when the definition of nighttime extubation was altered to the hours of midnight to 5 a.m. and when analyses were restricted to nonpalliative patients, according to Dr. Gershengorn, who disclosed that she had no relevant conflicts of interest.

SAN FRANCISCO – Mechanically ventilated patients in the intensive care unit (ICU) have poorer outcomes if extubated during the night instead of during the day, finds a retrospective cohort study reported at an international conference of the American Thoracic Society.

Overall, 20.1% of the nearly 98,000 adult patients studied were extubated during nighttime hours, between 7:00 p.m. and 7:00 a.m., according to data presented in a session and a related press conference.

Compared with patients extubated during daytime hours, patients extubated during nighttime hours had higher rates of ICU and hospital death, with the absolute difference ranging from 1.0% to 5.1%. Additionally, among those mechanically ventilated for at least 12 hours, nighttime extubation was associated with an absolute 2% increase in the risk of reintubation.

“I think this is the first large-scale study that looks at a practice that, although not as common as we thought it was, is still done about a fifth of the time and even with decreasing rates, is not a rare practice on our units,” commented lead author Dr. Hayley B. Gershengorn of the department of medicine (critical care) and the Saul R. Korey department of neurology at the Albert Einstein College of Medicine, New York.

“As we have increasing staffing [overnight] and maybe an increasing push to move people through our ICUs, we need to probably take some care because although we can’t demonstrate a causal link, it is quite concerning, this consistent finding of increased mortality and reintubation in these folks,” she said.

There are several possible reasons for the observed heightened risks of death and reintubation with nighttime extubation that could not be fully explored in the study, Dr. Gershengorn said.

“We were not able to identify the indication for extubation or discontinuation of mechanical ventilation. So one of the concerns that we have is that it’s probably more common that folks unintentionally extubate themselves or someone unintentionally extubates them overnight, when staffing is less,” she explained. “The other part, which we tried to adjust for but we don’t have perfect data on, is what is the staffing overnight,” including factors such as the ratio of nurses to patients and how many units an intensivist is covering, not just whether he or she is present.

“In terms of the reintubation risk being higher in the [group with longer duration of mechanical ventilation], the question I have is whether or not there is less comfort with somebody looking less well when there is less staff around, and whether or not there may be a quicker trigger to reintubate them if they don’t look so great,” she said.

The majority of intubated patients are unlikely to improve enough physiologically to prompt nighttime extubation rather than waiting until daytime, according to Dr. Gershengorn. But there are at least two groups whom clinicians might want to extubate at night.

One group is those who underwent elective surgery during the day. “They are waiting to come out of anesthesia, and the plan is to discontinue mechanical ventilation at the time that that occurs,” she explained. Another group is those who are agitated on the ventilator, require more sedation than usual, and suddenly awake at night. “These patients are really hard to keep comfortable. I can [sedate them] again and try this problem all over again tomorrow morning, or I can just bite the bullet and pull the tube out,” she said.

The investigators analyzed data from the Project IMPACT critical care medicine database, in which data are prospectively collected for benchmarking purposes. In all, they studied 97,844 mechanically ventilated adults from 165 medical and surgical ICUs across the United States between 2000 and 2009.

Results showed that nighttime extubation was more common among elective surgical patients, those coming from the operating room or a postanesthesia care unit, and those mechanically ventilated for less than 12 hours.

In a finding that Dr. Gershengorn described as surprising, there was a temporal trend by which the adjusted proportion of extubations performed at night actually decreased in more recent years during the study period.

The investigators next looked at outcomes among 10,279 propensity-matched pairs of patients, one member of the pair having been extubated during the night and the other having been extubated during the day.

Among those mechanically ventilated for less than 12 hours, nighttime extubation was associated with higher ICU mortality (5.6% vs. 4.6%; P = .025) and hospital mortality (8.3% vs. 7.0%; P = .014). Findings were inconsistent for length of stay, with nighttime extubation associated with a shorter ICU stay but a longer hospital stay.

Among patients mechanically ventilated for 12 hours or longer, those extubated during the night had a higher rate of reintubation (14.6% vs. 12.4%; P less than .001), as well as higher ICU mortality (11.2% vs. 6.1%; P less than .001) and hospital mortality (16.0% vs. 11.1%; P less than .001). Lengths of stay did not differ by extubation time of day in this group.

In sensitivity analyses, findings were similar when the definition of nighttime extubation was altered to the hours of midnight to 5 a.m. and when analyses were restricted to nonpalliative patients, according to Dr. Gershengorn, who disclosed that she had no relevant conflicts of interest.

SAN FRANCISCO – Mechanically ventilated patients in the intensive care unit (ICU) have poorer outcomes if extubated during the night instead of during the day, finds a retrospective cohort study reported at an international conference of the American Thoracic Society.

Overall, 20.1% of the nearly 98,000 adult patients studied were extubated during nighttime hours, between 7:00 p.m. and 7:00 a.m., according to data presented in a session and a related press conference.

Compared with patients extubated during daytime hours, patients extubated during nighttime hours had higher rates of ICU and hospital death, with the absolute difference ranging from 1.0% to 5.1%. Additionally, among those mechanically ventilated for at least 12 hours, nighttime extubation was associated with an absolute 2% increase in the risk of reintubation.

“I think this is the first large-scale study that looks at a practice that, although not as common as we thought it was, is still done about a fifth of the time and even with decreasing rates, is not a rare practice on our units,” commented lead author Dr. Hayley B. Gershengorn of the department of medicine (critical care) and the Saul R. Korey department of neurology at the Albert Einstein College of Medicine, New York.

“As we have increasing staffing [overnight] and maybe an increasing push to move people through our ICUs, we need to probably take some care because although we can’t demonstrate a causal link, it is quite concerning, this consistent finding of increased mortality and reintubation in these folks,” she said.

There are several possible reasons for the observed heightened risks of death and reintubation with nighttime extubation that could not be fully explored in the study, Dr. Gershengorn said.

“We were not able to identify the indication for extubation or discontinuation of mechanical ventilation. So one of the concerns that we have is that it’s probably more common that folks unintentionally extubate themselves or someone unintentionally extubates them overnight, when staffing is less,” she explained. “The other part, which we tried to adjust for but we don’t have perfect data on, is what is the staffing overnight,” including factors such as the ratio of nurses to patients and how many units an intensivist is covering, not just whether he or she is present.

“In terms of the reintubation risk being higher in the [group with longer duration of mechanical ventilation], the question I have is whether or not there is less comfort with somebody looking less well when there is less staff around, and whether or not there may be a quicker trigger to reintubate them if they don’t look so great,” she said.

The majority of intubated patients are unlikely to improve enough physiologically to prompt nighttime extubation rather than waiting until daytime, according to Dr. Gershengorn. But there are at least two groups whom clinicians might want to extubate at night.

One group is those who underwent elective surgery during the day. “They are waiting to come out of anesthesia, and the plan is to discontinue mechanical ventilation at the time that that occurs,” she explained. Another group is those who are agitated on the ventilator, require more sedation than usual, and suddenly awake at night. “These patients are really hard to keep comfortable. I can [sedate them] again and try this problem all over again tomorrow morning, or I can just bite the bullet and pull the tube out,” she said.

The investigators analyzed data from the Project IMPACT critical care medicine database, in which data are prospectively collected for benchmarking purposes. In all, they studied 97,844 mechanically ventilated adults from 165 medical and surgical ICUs across the United States between 2000 and 2009.

Results showed that nighttime extubation was more common among elective surgical patients, those coming from the operating room or a postanesthesia care unit, and those mechanically ventilated for less than 12 hours.

In a finding that Dr. Gershengorn described as surprising, there was a temporal trend by which the adjusted proportion of extubations performed at night actually decreased in more recent years during the study period.

The investigators next looked at outcomes among 10,279 propensity-matched pairs of patients, one member of the pair having been extubated during the night and the other having been extubated during the day.

Among those mechanically ventilated for less than 12 hours, nighttime extubation was associated with higher ICU mortality (5.6% vs. 4.6%; P = .025) and hospital mortality (8.3% vs. 7.0%; P = .014). Findings were inconsistent for length of stay, with nighttime extubation associated with a shorter ICU stay but a longer hospital stay.

Among patients mechanically ventilated for 12 hours or longer, those extubated during the night had a higher rate of reintubation (14.6% vs. 12.4%; P less than .001), as well as higher ICU mortality (11.2% vs. 6.1%; P less than .001) and hospital mortality (16.0% vs. 11.1%; P less than .001). Lengths of stay did not differ by extubation time of day in this group.

In sensitivity analyses, findings were similar when the definition of nighttime extubation was altered to the hours of midnight to 5 a.m. and when analyses were restricted to nonpalliative patients, according to Dr. Gershengorn, who disclosed that she had no relevant conflicts of interest.

CHICAGO – Atezolizumab, an antibody that targets PD-L1, achieves a median survival of 14.8 months in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma, according to findings of the IMvigor210 trial’s cohort 1. Researchers presented the findings this week at the annual meeting of the American Society of Clinical Oncology.

In an interview at the meeting, lead author Dr. Arjun Vasant Balar of the department of medicine at the New York University Langone Medical Center and director of genitourinary medical oncology at the NYU Perlmutter Cancer Center, discussed the study and its implications. In particular, he weighed in on key issues, such as whether PD-L1 status predicts benefit and where atezolizumab may ultimately fit into the treatment armamentarium for this disease.

tor@frontlinemedcom.com

On Twitter @OncologyPractic

CHICAGO – Atezolizumab, an antibody that targets PD-L1, achieves a median survival of 14.8 months in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma, according to findings of the IMvigor210 trial’s cohort 1. Researchers presented the findings this week at the annual meeting of the American Society of Clinical Oncology.

In an interview at the meeting, lead author Dr. Arjun Vasant Balar of the department of medicine at the New York University Langone Medical Center and director of genitourinary medical oncology at the NYU Perlmutter Cancer Center, discussed the study and its implications. In particular, he weighed in on key issues, such as whether PD-L1 status predicts benefit and where atezolizumab may ultimately fit into the treatment armamentarium for this disease.

tor@frontlinemedcom.com

On Twitter @OncologyPractic

CHICAGO – Atezolizumab, an antibody that targets PD-L1, achieves a median survival of 14.8 months in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma, according to findings of the IMvigor210 trial’s cohort 1. Researchers presented the findings this week at the annual meeting of the American Society of Clinical Oncology.

In an interview at the meeting, lead author Dr. Arjun Vasant Balar of the department of medicine at the New York University Langone Medical Center and director of genitourinary medical oncology at the NYU Perlmutter Cancer Center, discussed the study and its implications. In particular, he weighed in on key issues, such as whether PD-L1 status predicts benefit and where atezolizumab may ultimately fit into the treatment armamentarium for this disease.

tor@frontlinemedcom.com

On Twitter @OncologyPractic

CHICAGO – The phase III CASTOR trial tested addition of daratumumab—an anti-CD38 antibody—to bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Compared with the dual therapy, the triple therapy reduced the risk of progression or death by 61%, with little increase in toxicity, according to data reported at the annual meeting of the American Society of Clinical Oncology.

In an interview at the meeting, lead author Dr. Antonio Palumbo fielded key questions: Do some patients benefit more than others? Does the antibody prolong overall survival? And how much will it cost?

Dr. Palumbo is chief of the multiple myeloma Unit at the University of Torino, Italy.

CHICAGO – The phase III CASTOR trial tested addition of daratumumab—an anti-CD38 antibody—to bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Compared with the dual therapy, the triple therapy reduced the risk of progression or death by 61%, with little increase in toxicity, according to data reported at the annual meeting of the American Society of Clinical Oncology.

In an interview at the meeting, lead author Dr. Antonio Palumbo fielded key questions: Do some patients benefit more than others? Does the antibody prolong overall survival? And how much will it cost?

Dr. Palumbo is chief of the multiple myeloma Unit at the University of Torino, Italy.

CHICAGO – The phase III CASTOR trial tested addition of daratumumab—an anti-CD38 antibody—to bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Compared with the dual therapy, the triple therapy reduced the risk of progression or death by 61%, with little increase in toxicity, according to data reported at the annual meeting of the American Society of Clinical Oncology.

In an interview at the meeting, lead author Dr. Antonio Palumbo fielded key questions: Do some patients benefit more than others? Does the antibody prolong overall survival? And how much will it cost?

Dr. Palumbo is chief of the multiple myeloma Unit at the University of Torino, Italy.