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End-of-life cancer care by country
in the intensive care unit
A study of end-of-life cancer care practices in 7 countries suggests the US has the lowest proportion of deaths in the hospital and the lowest number of days in the hospital for patients in their last 6 months of life.
However, the US performed poorly in other aspects of care, particularly intensive care unit admissions and hospital expenditures.
The other countries included in the study were Belgium, Canada, England, Germany, the Netherlands, and Norway.
The research was published in JAMA.
Ezekiel J. Emanuel, MD, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues examined patterns of care, healthcare utilization, and expenditures for dying cancer patients in the 7 aforementioned countries.
The researchers first analyzed data from 2010 that included subjects older than 65 years of age who died with cancer.
The proportion of patients who died in the hospital was 22.2% in the US, 29.4% in the Netherlands, 38.3% in Germany, 41.7% in England, 44.7% in Norway, 51.2% in Belgium, and 52.1% in Canada.
In the last 180 days of life, the mean number of days in the hospital per capita was 27.7 in Belgium, 24.8 in Norway, 21.7 in Germany, 19 in Canada, 18.3 in England, 17.8 in the Netherlands, and 10.7 in the US.
The proportion of patients admitted to the intensive care unit in their last 180 days of life was 40.3% in the US, 18.5% in Belgium, 15.2% in Canada, 10.2% in the Netherlands, and 8.2% in Germany. Data were not available for England and Norway.
In the last 180 days of life, average per capita hospital expenditures (in USD) were higher in Canada ($21,840), Norway ($19,783), and the US ($18,500), intermediate in Germany ($16,221) and Belgium ($15,699), and lowest in the Netherlands ($10,936) and England ($9342).
Analyses that included decedents of any age, decedents older than 65 years of age with lung cancer, and decedents older than 65 years in the US and Germany from 2012 showed similar results.
The researchers said this suggests the differences observed were driven more by end-of-life care practices and organization rather than differences in cohort identification. 
in the intensive care unit
A study of end-of-life cancer care practices in 7 countries suggests the US has the lowest proportion of deaths in the hospital and the lowest number of days in the hospital for patients in their last 6 months of life.
However, the US performed poorly in other aspects of care, particularly intensive care unit admissions and hospital expenditures.
The other countries included in the study were Belgium, Canada, England, Germany, the Netherlands, and Norway.
The research was published in JAMA.
Ezekiel J. Emanuel, MD, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues examined patterns of care, healthcare utilization, and expenditures for dying cancer patients in the 7 aforementioned countries.
The researchers first analyzed data from 2010 that included subjects older than 65 years of age who died with cancer.
The proportion of patients who died in the hospital was 22.2% in the US, 29.4% in the Netherlands, 38.3% in Germany, 41.7% in England, 44.7% in Norway, 51.2% in Belgium, and 52.1% in Canada.
In the last 180 days of life, the mean number of days in the hospital per capita was 27.7 in Belgium, 24.8 in Norway, 21.7 in Germany, 19 in Canada, 18.3 in England, 17.8 in the Netherlands, and 10.7 in the US.
The proportion of patients admitted to the intensive care unit in their last 180 days of life was 40.3% in the US, 18.5% in Belgium, 15.2% in Canada, 10.2% in the Netherlands, and 8.2% in Germany. Data were not available for England and Norway.
In the last 180 days of life, average per capita hospital expenditures (in USD) were higher in Canada ($21,840), Norway ($19,783), and the US ($18,500), intermediate in Germany ($16,221) and Belgium ($15,699), and lowest in the Netherlands ($10,936) and England ($9342).
Analyses that included decedents of any age, decedents older than 65 years of age with lung cancer, and decedents older than 65 years in the US and Germany from 2012 showed similar results.
The researchers said this suggests the differences observed were driven more by end-of-life care practices and organization rather than differences in cohort identification.
in the intensive care unit
A study of end-of-life cancer care practices in 7 countries suggests the US has the lowest proportion of deaths in the hospital and the lowest number of days in the hospital for patients in their last 6 months of life.
However, the US performed poorly in other aspects of care, particularly intensive care unit admissions and hospital expenditures.
The other countries included in the study were Belgium, Canada, England, Germany, the Netherlands, and Norway.
The research was published in JAMA.
Ezekiel J. Emanuel, MD, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues examined patterns of care, healthcare utilization, and expenditures for dying cancer patients in the 7 aforementioned countries.
The researchers first analyzed data from 2010 that included subjects older than 65 years of age who died with cancer.
The proportion of patients who died in the hospital was 22.2% in the US, 29.4% in the Netherlands, 38.3% in Germany, 41.7% in England, 44.7% in Norway, 51.2% in Belgium, and 52.1% in Canada.
In the last 180 days of life, the mean number of days in the hospital per capita was 27.7 in Belgium, 24.8 in Norway, 21.7 in Germany, 19 in Canada, 18.3 in England, 17.8 in the Netherlands, and 10.7 in the US.
The proportion of patients admitted to the intensive care unit in their last 180 days of life was 40.3% in the US, 18.5% in Belgium, 15.2% in Canada, 10.2% in the Netherlands, and 8.2% in Germany. Data were not available for England and Norway.
In the last 180 days of life, average per capita hospital expenditures (in USD) were higher in Canada ($21,840), Norway ($19,783), and the US ($18,500), intermediate in Germany ($16,221) and Belgium ($15,699), and lowest in the Netherlands ($10,936) and England ($9342).
Analyses that included decedents of any age, decedents older than 65 years of age with lung cancer, and decedents older than 65 years in the US and Germany from 2012 showed similar results.
The researchers said this suggests the differences observed were driven more by end-of-life care practices and organization rather than differences in cohort identification.
Drug granted another breakthrough designation for CLL
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to the BCL-2 inhibitor venetoclax when given with rituximab to treat patients with relapsed or refractory chronic lymphocytic leukemia (CLL).
Venetoclax already had breakthrough designation from the FDA as single-agent treatment for patients with relapsed or refractory CLL and 17p deletion.
The drug was granted priority review for this indication as well.
Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.
The latest breakthrough designation for venetoclax is supported by a phase 2 study of the drug in combination with rituximab in patients with relapsed/refractory CLL. Results from this trial were presented at the 2015 ASH Annual Meeting (abstract 325).
Another phase 2 trial presented at that meeting (abstract LBA-6) showed that single-agent venetoclax is effective against CLL as well.
The drug has also proven active against other hematologic malignancies, including acute myeloid lekemia and multiple myeloma.
However, venetoclax has been shown to pose a risk of tumor lysis syndrome (TLS). In fact, TLS-related deaths temporarily halted enrollment in trials of venetoclax. But researchers discovered ways to reduce the risk of TLS, and the trials continued.
Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to the BCL-2 inhibitor venetoclax when given with rituximab to treat patients with relapsed or refractory chronic lymphocytic leukemia (CLL).
Venetoclax already had breakthrough designation from the FDA as single-agent treatment for patients with relapsed or refractory CLL and 17p deletion.
The drug was granted priority review for this indication as well.
Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.
The latest breakthrough designation for venetoclax is supported by a phase 2 study of the drug in combination with rituximab in patients with relapsed/refractory CLL. Results from this trial were presented at the 2015 ASH Annual Meeting (abstract 325).
Another phase 2 trial presented at that meeting (abstract LBA-6) showed that single-agent venetoclax is effective against CLL as well.
The drug has also proven active against other hematologic malignancies, including acute myeloid lekemia and multiple myeloma.
However, venetoclax has been shown to pose a risk of tumor lysis syndrome (TLS). In fact, TLS-related deaths temporarily halted enrollment in trials of venetoclax. But researchers discovered ways to reduce the risk of TLS, and the trials continued.
Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to the BCL-2 inhibitor venetoclax when given with rituximab to treat patients with relapsed or refractory chronic lymphocytic leukemia (CLL).
Venetoclax already had breakthrough designation from the FDA as single-agent treatment for patients with relapsed or refractory CLL and 17p deletion.
The drug was granted priority review for this indication as well.
Breakthrough therapy designation is designed to accelerate the development and review of medicines that demonstrate early clinical evidence of a substantial improvement over current treatment options for serious diseases.
The latest breakthrough designation for venetoclax is supported by a phase 2 study of the drug in combination with rituximab in patients with relapsed/refractory CLL. Results from this trial were presented at the 2015 ASH Annual Meeting (abstract 325).
Another phase 2 trial presented at that meeting (abstract LBA-6) showed that single-agent venetoclax is effective against CLL as well.
The drug has also proven active against other hematologic malignancies, including acute myeloid lekemia and multiple myeloma.
However, venetoclax has been shown to pose a risk of tumor lysis syndrome (TLS). In fact, TLS-related deaths temporarily halted enrollment in trials of venetoclax. But researchers discovered ways to reduce the risk of TLS, and the trials continued.
Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.
Protein may be therapeutic target for AML
and Matt McCormack, PhD
Photo courtesy of the
Walter and Eliza Hall
Institute of Medical Research
Preclinical research suggests the Hhex protein could be a cancer-specific therapeutic target for acute myeloid leukemia (AML).
Investigators discovered that loss of the Hhex protein halted leukemia cell growth and division in vitro and in vivo, but normal cells were unaffected by the loss of Hhex.
Matt McCormack, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and his colleagues relayed these findings in Genes and Development.
“There is an urgent need for new therapies to treat AML,” Dr McCormack said. “We showed blocking the Hhex protein could put the brakes on leukemia growth and completely eliminate AML in preclinical models. This could be targeted by new drugs to treat AML in humans.”
Specifically, the investigators found that Hhex was overexpressed in human AML, and the protein was essential for the maintenance of AML driven by the oncogenic fusion protein MLL-ENL and its downstream effectors, HoxA9 and Meis1.
However, Hhex was not required for normal myelopoiesis.
“Hhex is only essential for the leukemic cells, meaning we could target and treat leukemia without toxic effects on normal cells, avoiding many of the serious side effects that come with standard cancer treatments,” Dr McCormack said.
“We also know that most people with AML have increased levels of Hhex, often associated with adverse outcomes, further indicating it is an important target for new AML drugs.”
Dr McCormack and his colleagues also attempted to determine the mechanism by which Hhex promotes AML.
They found the protein represses the tumor suppressors p16INK4a and p19ARF in leukemic stem cells by regulating the Polycomb-repressive complex 2 (PRC2). They said that Hhex binds to the Cdkn2a locus and directly interacts with PRC2 to enable H3K27me3-mediated epigenetic repression.
“Hhex works by recruiting epigenetic factors to growth-control genes, effectively silencing them,” said author Ben Shields, PhD, also of the Walter and Eliza Hall Institute.
“This allows the leukemia cells to reproduce and accumulate more damage, contributing to the speed of AML progression.”
Dr McCormack said that although drugs inhibiting epigenetic modification have been tested against AML in the past, they have caused significant toxicity because their targets are also required for normal blood cell function.
“Unlike the epigenetic factors targeted previously, Hhex only regulates a small number of genes and is dispensable for normal blood cells,” Dr McCormack reiterated.
“This gives us a rare opportunity to kill AML cells without causing many side effects. We now hope to identify the critical regions of the Hhex protein that enable it to function, which will allow us to design much-needed new drugs to treat AML.”
and Matt McCormack, PhD
Photo courtesy of the
Walter and Eliza Hall
Institute of Medical Research
Preclinical research suggests the Hhex protein could be a cancer-specific therapeutic target for acute myeloid leukemia (AML).
Investigators discovered that loss of the Hhex protein halted leukemia cell growth and division in vitro and in vivo, but normal cells were unaffected by the loss of Hhex.
Matt McCormack, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and his colleagues relayed these findings in Genes and Development.
“There is an urgent need for new therapies to treat AML,” Dr McCormack said. “We showed blocking the Hhex protein could put the brakes on leukemia growth and completely eliminate AML in preclinical models. This could be targeted by new drugs to treat AML in humans.”
Specifically, the investigators found that Hhex was overexpressed in human AML, and the protein was essential for the maintenance of AML driven by the oncogenic fusion protein MLL-ENL and its downstream effectors, HoxA9 and Meis1.
However, Hhex was not required for normal myelopoiesis.
“Hhex is only essential for the leukemic cells, meaning we could target and treat leukemia without toxic effects on normal cells, avoiding many of the serious side effects that come with standard cancer treatments,” Dr McCormack said.
“We also know that most people with AML have increased levels of Hhex, often associated with adverse outcomes, further indicating it is an important target for new AML drugs.”
Dr McCormack and his colleagues also attempted to determine the mechanism by which Hhex promotes AML.
They found the protein represses the tumor suppressors p16INK4a and p19ARF in leukemic stem cells by regulating the Polycomb-repressive complex 2 (PRC2). They said that Hhex binds to the Cdkn2a locus and directly interacts with PRC2 to enable H3K27me3-mediated epigenetic repression.
“Hhex works by recruiting epigenetic factors to growth-control genes, effectively silencing them,” said author Ben Shields, PhD, also of the Walter and Eliza Hall Institute.
“This allows the leukemia cells to reproduce and accumulate more damage, contributing to the speed of AML progression.”
Dr McCormack said that although drugs inhibiting epigenetic modification have been tested against AML in the past, they have caused significant toxicity because their targets are also required for normal blood cell function.
“Unlike the epigenetic factors targeted previously, Hhex only regulates a small number of genes and is dispensable for normal blood cells,” Dr McCormack reiterated.
“This gives us a rare opportunity to kill AML cells without causing many side effects. We now hope to identify the critical regions of the Hhex protein that enable it to function, which will allow us to design much-needed new drugs to treat AML.”
and Matt McCormack, PhD
Photo courtesy of the
Walter and Eliza Hall
Institute of Medical Research
Preclinical research suggests the Hhex protein could be a cancer-specific therapeutic target for acute myeloid leukemia (AML).
Investigators discovered that loss of the Hhex protein halted leukemia cell growth and division in vitro and in vivo, but normal cells were unaffected by the loss of Hhex.
Matt McCormack, PhD, of the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia, and his colleagues relayed these findings in Genes and Development.
“There is an urgent need for new therapies to treat AML,” Dr McCormack said. “We showed blocking the Hhex protein could put the brakes on leukemia growth and completely eliminate AML in preclinical models. This could be targeted by new drugs to treat AML in humans.”
Specifically, the investigators found that Hhex was overexpressed in human AML, and the protein was essential for the maintenance of AML driven by the oncogenic fusion protein MLL-ENL and its downstream effectors, HoxA9 and Meis1.
However, Hhex was not required for normal myelopoiesis.
“Hhex is only essential for the leukemic cells, meaning we could target and treat leukemia without toxic effects on normal cells, avoiding many of the serious side effects that come with standard cancer treatments,” Dr McCormack said.
“We also know that most people with AML have increased levels of Hhex, often associated with adverse outcomes, further indicating it is an important target for new AML drugs.”
Dr McCormack and his colleagues also attempted to determine the mechanism by which Hhex promotes AML.
They found the protein represses the tumor suppressors p16INK4a and p19ARF in leukemic stem cells by regulating the Polycomb-repressive complex 2 (PRC2). They said that Hhex binds to the Cdkn2a locus and directly interacts with PRC2 to enable H3K27me3-mediated epigenetic repression.
“Hhex works by recruiting epigenetic factors to growth-control genes, effectively silencing them,” said author Ben Shields, PhD, also of the Walter and Eliza Hall Institute.
“This allows the leukemia cells to reproduce and accumulate more damage, contributing to the speed of AML progression.”
Dr McCormack said that although drugs inhibiting epigenetic modification have been tested against AML in the past, they have caused significant toxicity because their targets are also required for normal blood cell function.
“Unlike the epigenetic factors targeted previously, Hhex only regulates a small number of genes and is dispensable for normal blood cells,” Dr McCormack reiterated.
“This gives us a rare opportunity to kill AML cells without causing many side effects. We now hope to identify the critical regions of the Hhex protein that enable it to function, which will allow us to design much-needed new drugs to treat AML.”
FDA approves maintenance therapy for CLL
Photo courtesy of GSK
The US Food and Drug Administration (FDA) has approved the use of ofatumumab (Arzerra) as maintenance therapy for patients with chronic lymphocytic leukemia (CLL).
The drug can now be given for an extended period to patients who are in complete or partial response after receiving at least 2 lines of therapy for recurrent or progressive CLL.
Ofatumumab is also FDA-approved as a single agent to treat CLL that is refractory to fludarabine and alemtuzumab.
And the drug is approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.
The FDA granted the new approval for ofatumumab based on an interim analysis of the PROLONG study. The results suggested that ofatumumab maintenance can improve progression-free survival (PFS) in CLL patients when compared to observation.
Ofatumumab is marketed as Arzerra under a collaboration agreement between Genmab and Novartis. For more details on ofatumumab, see the full prescribing information.
PROLONG trial
The PROLONG trial was designed to compare ofatumumab maintenance to no further treatment in patients with a complete or partial response after second- or third-line treatment for CLL. Interim results of the study were presented at ASH 2014.
These results—in 474 patients—suggested that ofatumumab can significantly improve PFS. The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance therapy (P<0.0001).
There was no significant difference in the median overall survival, which was not reached in either treatment arm.
The researchers said there were no unexpected safety findings. The most common adverse events (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection.
Photo courtesy of GSK
The US Food and Drug Administration (FDA) has approved the use of ofatumumab (Arzerra) as maintenance therapy for patients with chronic lymphocytic leukemia (CLL).
The drug can now be given for an extended period to patients who are in complete or partial response after receiving at least 2 lines of therapy for recurrent or progressive CLL.
Ofatumumab is also FDA-approved as a single agent to treat CLL that is refractory to fludarabine and alemtuzumab.
And the drug is approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.
The FDA granted the new approval for ofatumumab based on an interim analysis of the PROLONG study. The results suggested that ofatumumab maintenance can improve progression-free survival (PFS) in CLL patients when compared to observation.
Ofatumumab is marketed as Arzerra under a collaboration agreement between Genmab and Novartis. For more details on ofatumumab, see the full prescribing information.
PROLONG trial
The PROLONG trial was designed to compare ofatumumab maintenance to no further treatment in patients with a complete or partial response after second- or third-line treatment for CLL. Interim results of the study were presented at ASH 2014.
These results—in 474 patients—suggested that ofatumumab can significantly improve PFS. The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance therapy (P<0.0001).
There was no significant difference in the median overall survival, which was not reached in either treatment arm.
The researchers said there were no unexpected safety findings. The most common adverse events (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection.
Photo courtesy of GSK
The US Food and Drug Administration (FDA) has approved the use of ofatumumab (Arzerra) as maintenance therapy for patients with chronic lymphocytic leukemia (CLL).
The drug can now be given for an extended period to patients who are in complete or partial response after receiving at least 2 lines of therapy for recurrent or progressive CLL.
Ofatumumab is also FDA-approved as a single agent to treat CLL that is refractory to fludarabine and alemtuzumab.
And the drug is approved for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.
The FDA granted the new approval for ofatumumab based on an interim analysis of the PROLONG study. The results suggested that ofatumumab maintenance can improve progression-free survival (PFS) in CLL patients when compared to observation.
Ofatumumab is marketed as Arzerra under a collaboration agreement between Genmab and Novartis. For more details on ofatumumab, see the full prescribing information.
PROLONG trial
The PROLONG trial was designed to compare ofatumumab maintenance to no further treatment in patients with a complete or partial response after second- or third-line treatment for CLL. Interim results of the study were presented at ASH 2014.
These results—in 474 patients—suggested that ofatumumab can significantly improve PFS. The median PFS was about 29 months in patients who received ofatumumab and about 15 months for patients who did not receive maintenance therapy (P<0.0001).
There was no significant difference in the median overall survival, which was not reached in either treatment arm.
The researchers said there were no unexpected safety findings. The most common adverse events (≥10%) were infusion reactions, neutropenia, and upper respiratory tract infection.
Drug approved to treat ALL in EU
The European Commission has granted marketing authorization for pegaspargase (Oncaspar) to be used as part of combination antineoplastic therapy for pediatric and adult patients with acute lymphoblastic leukemia (ALL).
The approval means the drug can be marketed for this indication in the 28 member countries of the European Union (EU), as well as Iceland, Liechtenstein, and Norway.
Pegaspargase was already approved for use in Argentina, Belarus, Germany, Kazakhstan, Poland, Russia, Ukraine, and the US.
“Oncaspar has been used as an integral component of the treatment regimen for pediatric and adult patients with ALL for many years, in Europe and worldwide,” said Martin Schrappe, of Schleswig-Holstein University Hospital in Kiel, Germany.
“Today’s marketing authorization will ensure that more patients across the EU will benefit from access to Oncaspar as part of a standard of care regimen.”
The drug is being developed by Baxalta Incorporated.
First-line ALL
Researchers have evaluated the safety and effectiveness of pegaspargase in a study of 118 pediatric patients (ages 1 to 9) with newly diagnosed ALL. The patients were randomized 1:1 to pegaspargase or native E coli L-asparaginase, both as part of combination therapy.
Asparagine depletion (magnitude and duration) was similar between the 2 treatment arms. Event-free survival rates were also similar (about 80% in both arms), but the study was not designed to evaluate differences in event-free survival.
Grade 3/4 adverse events occurring in the pegaspargase and native E coli L-asparaginase arms, respectively, were abnormal liver tests (5% and 8%), elevated transaminases (3% and 7%), hyperbilirubinemia (2% and 2%), hyperglycemia (5% and 3%), central nervous system thrombosis (3% and 3%), coagulopathy (2% and 5%), pancreatitis (2% and 2%), and clinical allergic reactions to asparaginase (2% and 0%).
Previously treated ALL
Researchers have evaluated the effectiveness of pegaspargase in 4 open-label studies of patients with a history of prior clinical allergic reaction to asparaginase. The studies enrolled a total of 42 patients with multiply relapsed acute leukemia (39 with ALL).
Patients received pegaspargase as a single agent or as part of multi-agent chemotherapy. The re-induction response rate was 50%—36% complete responses and 14% partial responses. Three responses occurred in patients who received single-agent pegaspargase.
Adverse event information on pegaspargase in relapsed ALL has been compiled from 5 clinical trials. The studies enrolled a total of 174 patients with relapsed ALL who received pegaspargase as a single agent or as part of combination therapy.
Sixty-two of the patients had prior hypersensitivity reactions to asparaginase, and 112 did not. Allergic reactions to pegaspargase occurred in 32% of previously hypersensitive patients and 10% of non-hypersensitive patients.
The most common adverse events observed in patients who received pegaspargase were clinical allergic reactions, elevated transaminases, hyperbilirubinemia, and coagulopathies.
The most common serious adverse events due to pegaspargase were thrombosis (4%), hyperglycemia requiring insulin therapy (3%), and pancreatitis (1%).
For more details on these trials and pegaspargase in general, see the product information.
The European Commission has granted marketing authorization for pegaspargase (Oncaspar) to be used as part of combination antineoplastic therapy for pediatric and adult patients with acute lymphoblastic leukemia (ALL).
The approval means the drug can be marketed for this indication in the 28 member countries of the European Union (EU), as well as Iceland, Liechtenstein, and Norway.
Pegaspargase was already approved for use in Argentina, Belarus, Germany, Kazakhstan, Poland, Russia, Ukraine, and the US.
“Oncaspar has been used as an integral component of the treatment regimen for pediatric and adult patients with ALL for many years, in Europe and worldwide,” said Martin Schrappe, of Schleswig-Holstein University Hospital in Kiel, Germany.
“Today’s marketing authorization will ensure that more patients across the EU will benefit from access to Oncaspar as part of a standard of care regimen.”
The drug is being developed by Baxalta Incorporated.
First-line ALL
Researchers have evaluated the safety and effectiveness of pegaspargase in a study of 118 pediatric patients (ages 1 to 9) with newly diagnosed ALL. The patients were randomized 1:1 to pegaspargase or native E coli L-asparaginase, both as part of combination therapy.
Asparagine depletion (magnitude and duration) was similar between the 2 treatment arms. Event-free survival rates were also similar (about 80% in both arms), but the study was not designed to evaluate differences in event-free survival.
Grade 3/4 adverse events occurring in the pegaspargase and native E coli L-asparaginase arms, respectively, were abnormal liver tests (5% and 8%), elevated transaminases (3% and 7%), hyperbilirubinemia (2% and 2%), hyperglycemia (5% and 3%), central nervous system thrombosis (3% and 3%), coagulopathy (2% and 5%), pancreatitis (2% and 2%), and clinical allergic reactions to asparaginase (2% and 0%).
Previously treated ALL
Researchers have evaluated the effectiveness of pegaspargase in 4 open-label studies of patients with a history of prior clinical allergic reaction to asparaginase. The studies enrolled a total of 42 patients with multiply relapsed acute leukemia (39 with ALL).
Patients received pegaspargase as a single agent or as part of multi-agent chemotherapy. The re-induction response rate was 50%—36% complete responses and 14% partial responses. Three responses occurred in patients who received single-agent pegaspargase.
Adverse event information on pegaspargase in relapsed ALL has been compiled from 5 clinical trials. The studies enrolled a total of 174 patients with relapsed ALL who received pegaspargase as a single agent or as part of combination therapy.
Sixty-two of the patients had prior hypersensitivity reactions to asparaginase, and 112 did not. Allergic reactions to pegaspargase occurred in 32% of previously hypersensitive patients and 10% of non-hypersensitive patients.
The most common adverse events observed in patients who received pegaspargase were clinical allergic reactions, elevated transaminases, hyperbilirubinemia, and coagulopathies.
The most common serious adverse events due to pegaspargase were thrombosis (4%), hyperglycemia requiring insulin therapy (3%), and pancreatitis (1%).
For more details on these trials and pegaspargase in general, see the product information.
The European Commission has granted marketing authorization for pegaspargase (Oncaspar) to be used as part of combination antineoplastic therapy for pediatric and adult patients with acute lymphoblastic leukemia (ALL).
The approval means the drug can be marketed for this indication in the 28 member countries of the European Union (EU), as well as Iceland, Liechtenstein, and Norway.
Pegaspargase was already approved for use in Argentina, Belarus, Germany, Kazakhstan, Poland, Russia, Ukraine, and the US.
“Oncaspar has been used as an integral component of the treatment regimen for pediatric and adult patients with ALL for many years, in Europe and worldwide,” said Martin Schrappe, of Schleswig-Holstein University Hospital in Kiel, Germany.
“Today’s marketing authorization will ensure that more patients across the EU will benefit from access to Oncaspar as part of a standard of care regimen.”
The drug is being developed by Baxalta Incorporated.
First-line ALL
Researchers have evaluated the safety and effectiveness of pegaspargase in a study of 118 pediatric patients (ages 1 to 9) with newly diagnosed ALL. The patients were randomized 1:1 to pegaspargase or native E coli L-asparaginase, both as part of combination therapy.
Asparagine depletion (magnitude and duration) was similar between the 2 treatment arms. Event-free survival rates were also similar (about 80% in both arms), but the study was not designed to evaluate differences in event-free survival.
Grade 3/4 adverse events occurring in the pegaspargase and native E coli L-asparaginase arms, respectively, were abnormal liver tests (5% and 8%), elevated transaminases (3% and 7%), hyperbilirubinemia (2% and 2%), hyperglycemia (5% and 3%), central nervous system thrombosis (3% and 3%), coagulopathy (2% and 5%), pancreatitis (2% and 2%), and clinical allergic reactions to asparaginase (2% and 0%).
Previously treated ALL
Researchers have evaluated the effectiveness of pegaspargase in 4 open-label studies of patients with a history of prior clinical allergic reaction to asparaginase. The studies enrolled a total of 42 patients with multiply relapsed acute leukemia (39 with ALL).
Patients received pegaspargase as a single agent or as part of multi-agent chemotherapy. The re-induction response rate was 50%—36% complete responses and 14% partial responses. Three responses occurred in patients who received single-agent pegaspargase.
Adverse event information on pegaspargase in relapsed ALL has been compiled from 5 clinical trials. The studies enrolled a total of 174 patients with relapsed ALL who received pegaspargase as a single agent or as part of combination therapy.
Sixty-two of the patients had prior hypersensitivity reactions to asparaginase, and 112 did not. Allergic reactions to pegaspargase occurred in 32% of previously hypersensitive patients and 10% of non-hypersensitive patients.
The most common adverse events observed in patients who received pegaspargase were clinical allergic reactions, elevated transaminases, hyperbilirubinemia, and coagulopathies.
The most common serious adverse events due to pegaspargase were thrombosis (4%), hyperglycemia requiring insulin therapy (3%), and pancreatitis (1%).
For more details on these trials and pegaspargase in general, see the product information.
Ofatumumab approved for extended treatment of CLL patients in complete or partial response
Ofatumumab has been approved for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive chronic lymphocytic leukemia (CLL), the U.S. Food and Drug Administration announced on Jan. 19.
Ofatumumab (Arzerra Injection, Novartis Pharmaceuticals) was previously approved for treatment-naive patients with CLL for whom fludarabine-based therapy was considered inappropriate and for patients with CLL refractory to fludarabine and alemtuzumab.
Approval of the new indication was based on the results of a randomized, open-label trial that found improved progression-free survival with ofatumumab as compared with observation in patients whose disease had a complete or partial response after at least two lines of prior therapy, the FDA said in a press release.
In the study, 238 patients were randomized to ofatumumab and 236 to observation. Patients in the ofatumumab arm had received a range of two to five prior therapies. The median progression-free survival was significantly longer with ofatumumab at 29.4 months (95% confidence interval, 26.2-34.2) than with observation at 15.2 months (95% CI, 11.8-18.8).
Of patients treated with ofatumumab, 33% reported serious adverse reactions. The most common were pneumonia, pyrexia, and neutropenia (including febrile neutropenia).
The recommended dose and schedule for ofatumumab therapy is 300 mg by intravenous infusion on day 1 followed by 1,000 mg on day 8, and then 7 weeks later, and then every 8 weeks thereafter for up to a maximum of 2 years.
Full prescribing information is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125326s062lbl.pdf.
Ofatumumab has been approved for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive chronic lymphocytic leukemia (CLL), the U.S. Food and Drug Administration announced on Jan. 19.
Ofatumumab (Arzerra Injection, Novartis Pharmaceuticals) was previously approved for treatment-naive patients with CLL for whom fludarabine-based therapy was considered inappropriate and for patients with CLL refractory to fludarabine and alemtuzumab.
Approval of the new indication was based on the results of a randomized, open-label trial that found improved progression-free survival with ofatumumab as compared with observation in patients whose disease had a complete or partial response after at least two lines of prior therapy, the FDA said in a press release.
In the study, 238 patients were randomized to ofatumumab and 236 to observation. Patients in the ofatumumab arm had received a range of two to five prior therapies. The median progression-free survival was significantly longer with ofatumumab at 29.4 months (95% confidence interval, 26.2-34.2) than with observation at 15.2 months (95% CI, 11.8-18.8).
Of patients treated with ofatumumab, 33% reported serious adverse reactions. The most common were pneumonia, pyrexia, and neutropenia (including febrile neutropenia).
The recommended dose and schedule for ofatumumab therapy is 300 mg by intravenous infusion on day 1 followed by 1,000 mg on day 8, and then 7 weeks later, and then every 8 weeks thereafter for up to a maximum of 2 years.
Full prescribing information is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125326s062lbl.pdf.
Ofatumumab has been approved for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive chronic lymphocytic leukemia (CLL), the U.S. Food and Drug Administration announced on Jan. 19.
Ofatumumab (Arzerra Injection, Novartis Pharmaceuticals) was previously approved for treatment-naive patients with CLL for whom fludarabine-based therapy was considered inappropriate and for patients with CLL refractory to fludarabine and alemtuzumab.
Approval of the new indication was based on the results of a randomized, open-label trial that found improved progression-free survival with ofatumumab as compared with observation in patients whose disease had a complete or partial response after at least two lines of prior therapy, the FDA said in a press release.
In the study, 238 patients were randomized to ofatumumab and 236 to observation. Patients in the ofatumumab arm had received a range of two to five prior therapies. The median progression-free survival was significantly longer with ofatumumab at 29.4 months (95% confidence interval, 26.2-34.2) than with observation at 15.2 months (95% CI, 11.8-18.8).
Of patients treated with ofatumumab, 33% reported serious adverse reactions. The most common were pneumonia, pyrexia, and neutropenia (including febrile neutropenia).
The recommended dose and schedule for ofatumumab therapy is 300 mg by intravenous infusion on day 1 followed by 1,000 mg on day 8, and then 7 weeks later, and then every 8 weeks thereafter for up to a maximum of 2 years.
Full prescribing information is available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125326s062lbl.pdf.
CIPN persists in female cancer survivors
Photo courtesy of NIH
SAN FRANCISCO—A study of female cancer survivors indicates that many still have chemotherapy-induced peripheral neuropathy (CIPN) symptoms years after completing cancer treatment.
In addition, CIPN was associated with worse physical functioning, poorer mobility, and a higher risk of falls.
Although more research is needed, investigators believe these findings may inform rehabilitation and fall prevention interventions for people with CIPN.
The findings were presented at the 2016 Cancer Survivorship Symposium (abstract 130*).
“We can’t dismiss neuropathy as a treatment side effect that goes away because symptoms persist for years in nearly half of women,” said Kerri M. Winters-Stone, PhD, of Oregon Health and Science University in Portland.
“While there are no effective treatments for this side effect, rehabilitative exercise programs may preserve physical functioning and mobility in the presence of neuropathy to help prevent falls and resulting injuries.”
For this study, Dr Winters-Stone and her colleagues assessed data from 512 women enrolled in exercise intervention trials designed to address fractures and falls in female cancer survivors. Most of the women had breast cancer, but there were also cases of lung, colorectal, ovarian, and hematologic cancers.
At an average of 6 years post-cancer diagnosis, 46% of the women (n=238) still reported some symptoms of CIPN, such as loss of feeling in their hands and feet.
The investigators noted significant relationships (P<0.01) between CIPN severity and gait speed, Physical Performance Battery score, self-reported physical functioning, and self-reported disability.
The team also compared measures of physical functioning in the women with CIPN to measures in women without CIPN (n=274). This analysis was adjusted for cancer type and time since diagnosis.
There was a significant difference (P<0.01) between the groups in one measure of lower-extremity fitness but not another. Namely, it took CIPN-positive women significantly longer to rise out of a chair (tested 5 times each). But women in both groups fared similarly on a test measuring maximal leg press strength.
The investigators also tested the women on mobility and physical functioning. The CIPN-positive women fared significantly worse than CIPN-negative women (P<0.01) when it came to walking speed, step number, stride length, percentage of gait cycle in double support, and Physical Performance Battery score. However, there was no significant difference between the groups with regard to base of support.
Finally, CIPN-positive women were significantly more likely than CIPN-negative women to report poor physical function and disability (P<0.01 for both). And CIPN-positive women had a higher rate of falls in the last year (P<0.01).
The investigators said women with CIPN have specific underlying impairments that put them at risk for falls, which may be different from the impairments that occur with other conditions or old age.
For example, CIPN does not cause muscle weakness, but it has a distinct effect on movement and gait patterns.
The team noted that the women with CIPN had difficulty rising from a chair, possibly because their brains do not get enough information from their feet about how quickly or forcefully to stand up.
Based on these findings, the investigators argued that commonly recommended exercise, such as walking, may be safer for women with CIPN when done on a treadmill with handrails because their altered gait puts them at an increased risk of falling.
The team also said that machine-based resistance training may not be beneficial because neuropathy does not appear to decrease leg strength. Instead, rehabilitation efforts should focus on improving balance during upright movement and specific gait training.
Furthermore, the investigators believe that, if the symptoms of CIPN are detected early, cancer treatments could potentially be changed to prevent these debilitating problems or early rehabilitation interventions could be started.
In addition, Dr Winters-Stone and her research team are developing a smartphone-driven device that patients can use to detect and quantify symptoms of neuropathy, such as gait and balance impairments.
*Data in the abstract differ from the presentation.
Photo courtesy of NIH
SAN FRANCISCO—A study of female cancer survivors indicates that many still have chemotherapy-induced peripheral neuropathy (CIPN) symptoms years after completing cancer treatment.
In addition, CIPN was associated with worse physical functioning, poorer mobility, and a higher risk of falls.
Although more research is needed, investigators believe these findings may inform rehabilitation and fall prevention interventions for people with CIPN.
The findings were presented at the 2016 Cancer Survivorship Symposium (abstract 130*).
“We can’t dismiss neuropathy as a treatment side effect that goes away because symptoms persist for years in nearly half of women,” said Kerri M. Winters-Stone, PhD, of Oregon Health and Science University in Portland.
“While there are no effective treatments for this side effect, rehabilitative exercise programs may preserve physical functioning and mobility in the presence of neuropathy to help prevent falls and resulting injuries.”
For this study, Dr Winters-Stone and her colleagues assessed data from 512 women enrolled in exercise intervention trials designed to address fractures and falls in female cancer survivors. Most of the women had breast cancer, but there were also cases of lung, colorectal, ovarian, and hematologic cancers.
At an average of 6 years post-cancer diagnosis, 46% of the women (n=238) still reported some symptoms of CIPN, such as loss of feeling in their hands and feet.
The investigators noted significant relationships (P<0.01) between CIPN severity and gait speed, Physical Performance Battery score, self-reported physical functioning, and self-reported disability.
The team also compared measures of physical functioning in the women with CIPN to measures in women without CIPN (n=274). This analysis was adjusted for cancer type and time since diagnosis.
There was a significant difference (P<0.01) between the groups in one measure of lower-extremity fitness but not another. Namely, it took CIPN-positive women significantly longer to rise out of a chair (tested 5 times each). But women in both groups fared similarly on a test measuring maximal leg press strength.
The investigators also tested the women on mobility and physical functioning. The CIPN-positive women fared significantly worse than CIPN-negative women (P<0.01) when it came to walking speed, step number, stride length, percentage of gait cycle in double support, and Physical Performance Battery score. However, there was no significant difference between the groups with regard to base of support.
Finally, CIPN-positive women were significantly more likely than CIPN-negative women to report poor physical function and disability (P<0.01 for both). And CIPN-positive women had a higher rate of falls in the last year (P<0.01).
The investigators said women with CIPN have specific underlying impairments that put them at risk for falls, which may be different from the impairments that occur with other conditions or old age.
For example, CIPN does not cause muscle weakness, but it has a distinct effect on movement and gait patterns.
The team noted that the women with CIPN had difficulty rising from a chair, possibly because their brains do not get enough information from their feet about how quickly or forcefully to stand up.
Based on these findings, the investigators argued that commonly recommended exercise, such as walking, may be safer for women with CIPN when done on a treadmill with handrails because their altered gait puts them at an increased risk of falling.
The team also said that machine-based resistance training may not be beneficial because neuropathy does not appear to decrease leg strength. Instead, rehabilitation efforts should focus on improving balance during upright movement and specific gait training.
Furthermore, the investigators believe that, if the symptoms of CIPN are detected early, cancer treatments could potentially be changed to prevent these debilitating problems or early rehabilitation interventions could be started.
In addition, Dr Winters-Stone and her research team are developing a smartphone-driven device that patients can use to detect and quantify symptoms of neuropathy, such as gait and balance impairments.
*Data in the abstract differ from the presentation.
Photo courtesy of NIH
SAN FRANCISCO—A study of female cancer survivors indicates that many still have chemotherapy-induced peripheral neuropathy (CIPN) symptoms years after completing cancer treatment.
In addition, CIPN was associated with worse physical functioning, poorer mobility, and a higher risk of falls.
Although more research is needed, investigators believe these findings may inform rehabilitation and fall prevention interventions for people with CIPN.
The findings were presented at the 2016 Cancer Survivorship Symposium (abstract 130*).
“We can’t dismiss neuropathy as a treatment side effect that goes away because symptoms persist for years in nearly half of women,” said Kerri M. Winters-Stone, PhD, of Oregon Health and Science University in Portland.
“While there are no effective treatments for this side effect, rehabilitative exercise programs may preserve physical functioning and mobility in the presence of neuropathy to help prevent falls and resulting injuries.”
For this study, Dr Winters-Stone and her colleagues assessed data from 512 women enrolled in exercise intervention trials designed to address fractures and falls in female cancer survivors. Most of the women had breast cancer, but there were also cases of lung, colorectal, ovarian, and hematologic cancers.
At an average of 6 years post-cancer diagnosis, 46% of the women (n=238) still reported some symptoms of CIPN, such as loss of feeling in their hands and feet.
The investigators noted significant relationships (P<0.01) between CIPN severity and gait speed, Physical Performance Battery score, self-reported physical functioning, and self-reported disability.
The team also compared measures of physical functioning in the women with CIPN to measures in women without CIPN (n=274). This analysis was adjusted for cancer type and time since diagnosis.
There was a significant difference (P<0.01) between the groups in one measure of lower-extremity fitness but not another. Namely, it took CIPN-positive women significantly longer to rise out of a chair (tested 5 times each). But women in both groups fared similarly on a test measuring maximal leg press strength.
The investigators also tested the women on mobility and physical functioning. The CIPN-positive women fared significantly worse than CIPN-negative women (P<0.01) when it came to walking speed, step number, stride length, percentage of gait cycle in double support, and Physical Performance Battery score. However, there was no significant difference between the groups with regard to base of support.
Finally, CIPN-positive women were significantly more likely than CIPN-negative women to report poor physical function and disability (P<0.01 for both). And CIPN-positive women had a higher rate of falls in the last year (P<0.01).
The investigators said women with CIPN have specific underlying impairments that put them at risk for falls, which may be different from the impairments that occur with other conditions or old age.
For example, CIPN does not cause muscle weakness, but it has a distinct effect on movement and gait patterns.
The team noted that the women with CIPN had difficulty rising from a chair, possibly because their brains do not get enough information from their feet about how quickly or forcefully to stand up.
Based on these findings, the investigators argued that commonly recommended exercise, such as walking, may be safer for women with CIPN when done on a treadmill with handrails because their altered gait puts them at an increased risk of falling.
The team also said that machine-based resistance training may not be beneficial because neuropathy does not appear to decrease leg strength. Instead, rehabilitation efforts should focus on improving balance during upright movement and specific gait training.
Furthermore, the investigators believe that, if the symptoms of CIPN are detected early, cancer treatments could potentially be changed to prevent these debilitating problems or early rehabilitation interventions could be started.
In addition, Dr Winters-Stone and her research team are developing a smartphone-driven device that patients can use to detect and quantify symptoms of neuropathy, such as gait and balance impairments.
*Data in the abstract differ from the presentation.
Cancer survival tied to reduction in treatment
Photo by Bill Branson
Results of a large study suggest that long-term survivors of childhood cancer are living longer, partly due to a reduction in the use of certain treatments.
The 15-year death rate among the more than 34,000 childhood cancer survivors studied decreased steadily from 1970 onward.
And this decline coincided with changes in pediatric cancer therapy, including reductions in the use and dose of radiation therapy and anthracyclines.
These therapies are known to put cancer survivors at increased risk for developing second malignancies, heart failure, and other serious health problems.
“This study is the first to show that younger survivors from more recent treatment eras are less likely to die from the late effects of cancer treatment and more likely to enjoy longer lives,” said study author Greg Armstrong, MD, of St. Jude Children's Research Hospital in Memphis, Tennessee.
He and his colleagues reported these results in NEJM.
The study included 34,033 subjects who had been diagnosed with cancer and received treatment between 1970 and 1999 when they were age 20 or younger. All patients lived at least 5 years after their cancers were discovered and were considered long-term survivors.
Changes in mortality
At a median follow-up of 21 years (range, 5 to 38), there were 3958 deaths. Forty-one percent of deaths (n=1618) were considered health-related. This included 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes.
The 15-year death rate (death from any cause) fell from 12.4% in the early 1970s to 6% in the 1990s (P<0.001). During the same period, the rate of death from health-related causes fell from 3.5% to 2.1% (P<0.001).
The researchers said there were significant reductions across treatment eras in the rates of death from any health-related cause among patients with acute lymphoblastic leukemia (ALL), Hodgkin lymphoma (HL), Wilms’ tumor, and astrocytoma, but not among patients with other cancers.
The rate of health-related death among ALL patients fell from 3.2% in the early 1970s to 2.1% in the 1990s (P<0.001). The rate fell from 5.3% to 2.6% (P=0.006) for HL patients, from 2.6% to 0.4% (P=0.005) for Wilms’ tumor patients, and from 4.7% to 1.8% (P=0.02) for astrocytoma patients.
The researchers said these reductions in mortality were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04).
Treatment changes
The overall use of anthracyclines fell from 73% in the 1970s to 42% in the 1990s. And the use of any radiation decreased from 77% to 41%.
The use of cranial radiotherapy for ALL fell from 85% to 19%. The use of abdominal radiotherapy for Wilms’ tumor decreased from 78% to 43%. And the use of chest radiotherapy for HL fell from 87% to 61%.
The researchers noted that temporal reductions in 15-year rates of death from health-related causes followed temporal reductions in therapeutic exposure for patients with ALL, HL, Wilms’ tumor, and astrocytoma.
However, when the team adjusted their analysis for therapy (eg, anthracycline dose), the effect of the treatment era on the relative rate of death from health-related causes was attenuated in ALL (unadjusted relative rate=0.88, adjusted relative rate=1.02) and Wilms’ tumor (0.68 and 0.80, respectively) but not in HL (0.79 in both models) and astrocytoma (0.81 and 0.82, respectively).
Still, the researchers said the results of this study suggest the strategy of lowering therapeutic exposure has contributed to the decline in late mortality among 5-year survivors of childhood cancer.
Photo by Bill Branson
Results of a large study suggest that long-term survivors of childhood cancer are living longer, partly due to a reduction in the use of certain treatments.
The 15-year death rate among the more than 34,000 childhood cancer survivors studied decreased steadily from 1970 onward.
And this decline coincided with changes in pediatric cancer therapy, including reductions in the use and dose of radiation therapy and anthracyclines.
These therapies are known to put cancer survivors at increased risk for developing second malignancies, heart failure, and other serious health problems.
“This study is the first to show that younger survivors from more recent treatment eras are less likely to die from the late effects of cancer treatment and more likely to enjoy longer lives,” said study author Greg Armstrong, MD, of St. Jude Children's Research Hospital in Memphis, Tennessee.
He and his colleagues reported these results in NEJM.
The study included 34,033 subjects who had been diagnosed with cancer and received treatment between 1970 and 1999 when they were age 20 or younger. All patients lived at least 5 years after their cancers were discovered and were considered long-term survivors.
Changes in mortality
At a median follow-up of 21 years (range, 5 to 38), there were 3958 deaths. Forty-one percent of deaths (n=1618) were considered health-related. This included 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes.
The 15-year death rate (death from any cause) fell from 12.4% in the early 1970s to 6% in the 1990s (P<0.001). During the same period, the rate of death from health-related causes fell from 3.5% to 2.1% (P<0.001).
The researchers said there were significant reductions across treatment eras in the rates of death from any health-related cause among patients with acute lymphoblastic leukemia (ALL), Hodgkin lymphoma (HL), Wilms’ tumor, and astrocytoma, but not among patients with other cancers.
The rate of health-related death among ALL patients fell from 3.2% in the early 1970s to 2.1% in the 1990s (P<0.001). The rate fell from 5.3% to 2.6% (P=0.006) for HL patients, from 2.6% to 0.4% (P=0.005) for Wilms’ tumor patients, and from 4.7% to 1.8% (P=0.02) for astrocytoma patients.
The researchers said these reductions in mortality were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04).
Treatment changes
The overall use of anthracyclines fell from 73% in the 1970s to 42% in the 1990s. And the use of any radiation decreased from 77% to 41%.
The use of cranial radiotherapy for ALL fell from 85% to 19%. The use of abdominal radiotherapy for Wilms’ tumor decreased from 78% to 43%. And the use of chest radiotherapy for HL fell from 87% to 61%.
The researchers noted that temporal reductions in 15-year rates of death from health-related causes followed temporal reductions in therapeutic exposure for patients with ALL, HL, Wilms’ tumor, and astrocytoma.
However, when the team adjusted their analysis for therapy (eg, anthracycline dose), the effect of the treatment era on the relative rate of death from health-related causes was attenuated in ALL (unadjusted relative rate=0.88, adjusted relative rate=1.02) and Wilms’ tumor (0.68 and 0.80, respectively) but not in HL (0.79 in both models) and astrocytoma (0.81 and 0.82, respectively).
Still, the researchers said the results of this study suggest the strategy of lowering therapeutic exposure has contributed to the decline in late mortality among 5-year survivors of childhood cancer.
Photo by Bill Branson
Results of a large study suggest that long-term survivors of childhood cancer are living longer, partly due to a reduction in the use of certain treatments.
The 15-year death rate among the more than 34,000 childhood cancer survivors studied decreased steadily from 1970 onward.
And this decline coincided with changes in pediatric cancer therapy, including reductions in the use and dose of radiation therapy and anthracyclines.
These therapies are known to put cancer survivors at increased risk for developing second malignancies, heart failure, and other serious health problems.
“This study is the first to show that younger survivors from more recent treatment eras are less likely to die from the late effects of cancer treatment and more likely to enjoy longer lives,” said study author Greg Armstrong, MD, of St. Jude Children's Research Hospital in Memphis, Tennessee.
He and his colleagues reported these results in NEJM.
The study included 34,033 subjects who had been diagnosed with cancer and received treatment between 1970 and 1999 when they were age 20 or younger. All patients lived at least 5 years after their cancers were discovered and were considered long-term survivors.
Changes in mortality
At a median follow-up of 21 years (range, 5 to 38), there were 3958 deaths. Forty-one percent of deaths (n=1618) were considered health-related. This included 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes.
The 15-year death rate (death from any cause) fell from 12.4% in the early 1970s to 6% in the 1990s (P<0.001). During the same period, the rate of death from health-related causes fell from 3.5% to 2.1% (P<0.001).
The researchers said there were significant reductions across treatment eras in the rates of death from any health-related cause among patients with acute lymphoblastic leukemia (ALL), Hodgkin lymphoma (HL), Wilms’ tumor, and astrocytoma, but not among patients with other cancers.
The rate of health-related death among ALL patients fell from 3.2% in the early 1970s to 2.1% in the 1990s (P<0.001). The rate fell from 5.3% to 2.6% (P=0.006) for HL patients, from 2.6% to 0.4% (P=0.005) for Wilms’ tumor patients, and from 4.7% to 1.8% (P=0.02) for astrocytoma patients.
The researchers said these reductions in mortality were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04).
Treatment changes
The overall use of anthracyclines fell from 73% in the 1970s to 42% in the 1990s. And the use of any radiation decreased from 77% to 41%.
The use of cranial radiotherapy for ALL fell from 85% to 19%. The use of abdominal radiotherapy for Wilms’ tumor decreased from 78% to 43%. And the use of chest radiotherapy for HL fell from 87% to 61%.
The researchers noted that temporal reductions in 15-year rates of death from health-related causes followed temporal reductions in therapeutic exposure for patients with ALL, HL, Wilms’ tumor, and astrocytoma.
However, when the team adjusted their analysis for therapy (eg, anthracycline dose), the effect of the treatment era on the relative rate of death from health-related causes was attenuated in ALL (unadjusted relative rate=0.88, adjusted relative rate=1.02) and Wilms’ tumor (0.68 and 0.80, respectively) but not in HL (0.79 in both models) and astrocytoma (0.81 and 0.82, respectively).
Still, the researchers said the results of this study suggest the strategy of lowering therapeutic exposure has contributed to the decline in late mortality among 5-year survivors of childhood cancer.
Predicting transformation from MDS to AML
Photo courtesy of
McMaster University
Research published in Cancer Cell suggests a molecular signature can be used to predict which patients with myelodysplastic syndromes (MDS) will develop acute myeloid leukemia (AML).
Investigators found that progressive removal of glycogen synthase kinase-3 (GSK-3) signaling via GSK-3β deletion in hematopoietic stem cells (HSCs) results in an MDS-like state.
And when both GSK-3β and GSK-3α are deleted, AML develops.
“We’ve found that the transition from healthy to cancerous blood stem cells happens in clear, compartmentalized steps,” said study author Mick Bhatia, PhD, of McMaster University in Hamilton, Ontario, Canada. “We’ve identified 2 steps in that staircase.”
Specifically, the investigators found that deleting GSK-3β in HSCs led to the generation of self-renewing cells dubbed MDS-initiating cells. These cells proved capable of sustaining MDS in vivo.
Next, the team found that GSK-3β deletion drives Wnt/Akt/mTOR signaling and can induce AML in the absence of GSK-3α.
They noted that GSK-3α has no biological impact on hematopoiesis, but GSK-3α deletion is necessary for the evolution of MDS to AML that occurs in the absence of GSK-3β.
The investigators then defined a molecular signature of GSK-3β-deficient HSCs that could predict transformation to AML in patients with MDS.
The team tested the utility of this 63-gene signature using blood samples that were previously collected from patients with MDS, some of whom ultimately developed AML. The results showed the signature could accurately predict which patients would develop AML and which would not.
“[O]ur next step is to go beyond better predictive measures for the development of a blood cancer and use this predictive gene expression as a target for drugs to prevent AML from developing altogether,” Dr Bhatia said. “This will be part of a new era of genetic-based drug discovery.”
Photo courtesy of
McMaster University
Research published in Cancer Cell suggests a molecular signature can be used to predict which patients with myelodysplastic syndromes (MDS) will develop acute myeloid leukemia (AML).
Investigators found that progressive removal of glycogen synthase kinase-3 (GSK-3) signaling via GSK-3β deletion in hematopoietic stem cells (HSCs) results in an MDS-like state.
And when both GSK-3β and GSK-3α are deleted, AML develops.
“We’ve found that the transition from healthy to cancerous blood stem cells happens in clear, compartmentalized steps,” said study author Mick Bhatia, PhD, of McMaster University in Hamilton, Ontario, Canada. “We’ve identified 2 steps in that staircase.”
Specifically, the investigators found that deleting GSK-3β in HSCs led to the generation of self-renewing cells dubbed MDS-initiating cells. These cells proved capable of sustaining MDS in vivo.
Next, the team found that GSK-3β deletion drives Wnt/Akt/mTOR signaling and can induce AML in the absence of GSK-3α.
They noted that GSK-3α has no biological impact on hematopoiesis, but GSK-3α deletion is necessary for the evolution of MDS to AML that occurs in the absence of GSK-3β.
The investigators then defined a molecular signature of GSK-3β-deficient HSCs that could predict transformation to AML in patients with MDS.
The team tested the utility of this 63-gene signature using blood samples that were previously collected from patients with MDS, some of whom ultimately developed AML. The results showed the signature could accurately predict which patients would develop AML and which would not.
“[O]ur next step is to go beyond better predictive measures for the development of a blood cancer and use this predictive gene expression as a target for drugs to prevent AML from developing altogether,” Dr Bhatia said. “This will be part of a new era of genetic-based drug discovery.”
Photo courtesy of
McMaster University
Research published in Cancer Cell suggests a molecular signature can be used to predict which patients with myelodysplastic syndromes (MDS) will develop acute myeloid leukemia (AML).
Investigators found that progressive removal of glycogen synthase kinase-3 (GSK-3) signaling via GSK-3β deletion in hematopoietic stem cells (HSCs) results in an MDS-like state.
And when both GSK-3β and GSK-3α are deleted, AML develops.
“We’ve found that the transition from healthy to cancerous blood stem cells happens in clear, compartmentalized steps,” said study author Mick Bhatia, PhD, of McMaster University in Hamilton, Ontario, Canada. “We’ve identified 2 steps in that staircase.”
Specifically, the investigators found that deleting GSK-3β in HSCs led to the generation of self-renewing cells dubbed MDS-initiating cells. These cells proved capable of sustaining MDS in vivo.
Next, the team found that GSK-3β deletion drives Wnt/Akt/mTOR signaling and can induce AML in the absence of GSK-3α.
They noted that GSK-3α has no biological impact on hematopoiesis, but GSK-3α deletion is necessary for the evolution of MDS to AML that occurs in the absence of GSK-3β.
The investigators then defined a molecular signature of GSK-3β-deficient HSCs that could predict transformation to AML in patients with MDS.
The team tested the utility of this 63-gene signature using blood samples that were previously collected from patients with MDS, some of whom ultimately developed AML. The results showed the signature could accurately predict which patients would develop AML and which would not.
“[O]ur next step is to go beyond better predictive measures for the development of a blood cancer and use this predictive gene expression as a target for drugs to prevent AML from developing altogether,” Dr Bhatia said. “This will be part of a new era of genetic-based drug discovery.”
Venetoclax gets 79% overall response rate in high-risk CLL
ORLANDO – Venetoclax monotherapy achieved an overall response rate of 79% in a high-risk population of 107 patients with relapsed or refractory del(17p) chronic lymphocytic leukemia, Dr. Stephan Stilgenbauer reported in a late-breaking abstract at the annual meeting of the American Society of Hematology.
Of the 85 responders, the response was maintained at 1 year in 85%. Of the 45 patients assessed for minimal residual disease in the blood, 18 achieved MRD negativity. Ten of these 18 patients also had bone marrow assessments and six were MRD negative.
Dr. Stilgenbauer of the University of Ulm (Germany), discussed the implications of the phase II study findings in our exclusive interview at ASH, as well as phase III study plans and the use of venetoclax in combination therapies.
He receives honoraria or research funding from a wide range of companies, including AbbVie and Genentech, the companies collaborating on the development of venetoclax.
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ORLANDO – Venetoclax monotherapy achieved an overall response rate of 79% in a high-risk population of 107 patients with relapsed or refractory del(17p) chronic lymphocytic leukemia, Dr. Stephan Stilgenbauer reported in a late-breaking abstract at the annual meeting of the American Society of Hematology.
Of the 85 responders, the response was maintained at 1 year in 85%. Of the 45 patients assessed for minimal residual disease in the blood, 18 achieved MRD negativity. Ten of these 18 patients also had bone marrow assessments and six were MRD negative.
Dr. Stilgenbauer of the University of Ulm (Germany), discussed the implications of the phase II study findings in our exclusive interview at ASH, as well as phase III study plans and the use of venetoclax in combination therapies.
He receives honoraria or research funding from a wide range of companies, including AbbVie and Genentech, the companies collaborating on the development of venetoclax.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @maryjodales
ORLANDO – Venetoclax monotherapy achieved an overall response rate of 79% in a high-risk population of 107 patients with relapsed or refractory del(17p) chronic lymphocytic leukemia, Dr. Stephan Stilgenbauer reported in a late-breaking abstract at the annual meeting of the American Society of Hematology.
Of the 85 responders, the response was maintained at 1 year in 85%. Of the 45 patients assessed for minimal residual disease in the blood, 18 achieved MRD negativity. Ten of these 18 patients also had bone marrow assessments and six were MRD negative.
Dr. Stilgenbauer of the University of Ulm (Germany), discussed the implications of the phase II study findings in our exclusive interview at ASH, as well as phase III study plans and the use of venetoclax in combination therapies.
He receives honoraria or research funding from a wide range of companies, including AbbVie and Genentech, the companies collaborating on the development of venetoclax.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @maryjodales
AT ASH 2015
