User login
Appalachia has higher cancer incidence than rest of US
receiving chemotherapy
Photo by Rhoda Baer
New research suggests that people living in the Appalachian region of the US are more likely to develop cancer than people in the rest of the country.
The study showed that Appalachians had a significantly higher incidence of cancer overall and higher rates of many solid tumor malignancies.
However, lymphoma rates were similar between Appalachians and non-Appalachians, and Appalachians had a significantly lower rate of myeloma.
This research was published in Cancer Epidemiology, Biomarkers & Prevention.
“The Appalachian region, which extends from parts of New York to Mississippi, spans 420 counties in 13 US states, and about 25 million people reside in this area,” said study author Reda Wilson, MPH, of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.
“This region is primarily made up of rural areas, with persistent poverty levels that are at least 20%, which is higher than the national average.”
In 2007, the CDC’s National Program of Cancer Registries (NPCR) published a comprehensive evaluation of cancer incidence rates in Appalachia between 2001 and 2003.
The data showed higher cancer rates in Appalachia than in the rest of the US. However, this publication had some shortcomings, including data that were not available for analysis.
“The current analyses reported here were performed to update the earlier evaluation by expanding the diagnosis years from 2004 to 2011 and including data on 100% of the Appalachian and non-Appalachian populations,” Wilson said.
For this study, Wilson and her colleagues used data from the NPCR and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Together, NPCR and SEER cover 100% of the US population.
The researchers analyzed the Appalachian population by region (north, central, and south Appalachia), gender, race (black and white only), and Appalachian Regional Commission-designated economic status (distressed, at-risk, transitional, competitive, and attainment). And the team compared these data with data on the non-Appalachian population.
The results showed that cancer incidence rates (IRs) were elevated among Appalachians regardless of how they were categorized. The IRs were per 100,000 people, age-adjusted to the 2000 US standard population.
The IR for all cancers was 565.8 for males in Appalachia and 543.0 for non-Appalachian males (P<0.05). And the cancer IRs for females were 428.7 in Appalachia and 418.2 outside the region (P<0.05).
There was no significant difference between the regions in IRs for lymphomas. The Hodgkin lymphoma IRs were 3.1 in Appalachian males, 3.2 in non-Appalachian males, and 2.5 for females in both regions.
The non-Hodgkin lymphoma IRs were 23.3 in Appalachian males, 23.4 in non-Appalachian males, 16.4 in Appalachian females, and 16.3 in non-Appalachian females.
Myeloma IRs were significantly lower in Appalachia (P<0.05). The myeloma IRs were 7.3 in Appalachian males, 7.5 in non-Appalachian males, 4.7 in Appalachian females, and 4.9 in non-Appalachian females.
There was no significant difference in leukemia IRs among males, but females in Appalachia had a significantly higher leukemia IR (P<0.05). The leukemia IRs were 16.9 in Appalachian males, 16.7 in non-Appalachian males, 10.4 in Appalachian females, and 10.2 in non-Appalachian females.
“Appalachia continues to have higher cancer incidence rates than the rest of the country,” Wilson said. “But a promising finding is that we’re seeing the gap narrow in the incidence rates between Appalachia and non-Appalachia since the 2007 analysis, with the exception of cancers of the oral cavity and pharynx, larynx, lung and bronchus, and thyroid.”
“This study helps identify types of cancer in the Appalachian region that could be reduced through more evidence-based screening and detection. Our study also emphasizes the importance of lifestyle changes needed to prevent and reduce cancer burden.”
The researchers noted that this study did not differentiate urban versus rural areas within each county, and data on screening and risk factors were based on self-reported responses.
Furthermore, cancer IRs were calculated for all ages combined and were not evaluated by age groups. Future analyses will be targeted toward capturing these finer details, Wilson said. 
receiving chemotherapy
Photo by Rhoda Baer
New research suggests that people living in the Appalachian region of the US are more likely to develop cancer than people in the rest of the country.
The study showed that Appalachians had a significantly higher incidence of cancer overall and higher rates of many solid tumor malignancies.
However, lymphoma rates were similar between Appalachians and non-Appalachians, and Appalachians had a significantly lower rate of myeloma.
This research was published in Cancer Epidemiology, Biomarkers & Prevention.
“The Appalachian region, which extends from parts of New York to Mississippi, spans 420 counties in 13 US states, and about 25 million people reside in this area,” said study author Reda Wilson, MPH, of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.
“This region is primarily made up of rural areas, with persistent poverty levels that are at least 20%, which is higher than the national average.”
In 2007, the CDC’s National Program of Cancer Registries (NPCR) published a comprehensive evaluation of cancer incidence rates in Appalachia between 2001 and 2003.
The data showed higher cancer rates in Appalachia than in the rest of the US. However, this publication had some shortcomings, including data that were not available for analysis.
“The current analyses reported here were performed to update the earlier evaluation by expanding the diagnosis years from 2004 to 2011 and including data on 100% of the Appalachian and non-Appalachian populations,” Wilson said.
For this study, Wilson and her colleagues used data from the NPCR and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Together, NPCR and SEER cover 100% of the US population.
The researchers analyzed the Appalachian population by region (north, central, and south Appalachia), gender, race (black and white only), and Appalachian Regional Commission-designated economic status (distressed, at-risk, transitional, competitive, and attainment). And the team compared these data with data on the non-Appalachian population.
The results showed that cancer incidence rates (IRs) were elevated among Appalachians regardless of how they were categorized. The IRs were per 100,000 people, age-adjusted to the 2000 US standard population.
The IR for all cancers was 565.8 for males in Appalachia and 543.0 for non-Appalachian males (P<0.05). And the cancer IRs for females were 428.7 in Appalachia and 418.2 outside the region (P<0.05).
There was no significant difference between the regions in IRs for lymphomas. The Hodgkin lymphoma IRs were 3.1 in Appalachian males, 3.2 in non-Appalachian males, and 2.5 for females in both regions.
The non-Hodgkin lymphoma IRs were 23.3 in Appalachian males, 23.4 in non-Appalachian males, 16.4 in Appalachian females, and 16.3 in non-Appalachian females.
Myeloma IRs were significantly lower in Appalachia (P<0.05). The myeloma IRs were 7.3 in Appalachian males, 7.5 in non-Appalachian males, 4.7 in Appalachian females, and 4.9 in non-Appalachian females.
There was no significant difference in leukemia IRs among males, but females in Appalachia had a significantly higher leukemia IR (P<0.05). The leukemia IRs were 16.9 in Appalachian males, 16.7 in non-Appalachian males, 10.4 in Appalachian females, and 10.2 in non-Appalachian females.
“Appalachia continues to have higher cancer incidence rates than the rest of the country,” Wilson said. “But a promising finding is that we’re seeing the gap narrow in the incidence rates between Appalachia and non-Appalachia since the 2007 analysis, with the exception of cancers of the oral cavity and pharynx, larynx, lung and bronchus, and thyroid.”
“This study helps identify types of cancer in the Appalachian region that could be reduced through more evidence-based screening and detection. Our study also emphasizes the importance of lifestyle changes needed to prevent and reduce cancer burden.”
The researchers noted that this study did not differentiate urban versus rural areas within each county, and data on screening and risk factors were based on self-reported responses.
Furthermore, cancer IRs were calculated for all ages combined and were not evaluated by age groups. Future analyses will be targeted toward capturing these finer details, Wilson said.
receiving chemotherapy
Photo by Rhoda Baer
New research suggests that people living in the Appalachian region of the US are more likely to develop cancer than people in the rest of the country.
The study showed that Appalachians had a significantly higher incidence of cancer overall and higher rates of many solid tumor malignancies.
However, lymphoma rates were similar between Appalachians and non-Appalachians, and Appalachians had a significantly lower rate of myeloma.
This research was published in Cancer Epidemiology, Biomarkers & Prevention.
“The Appalachian region, which extends from parts of New York to Mississippi, spans 420 counties in 13 US states, and about 25 million people reside in this area,” said study author Reda Wilson, MPH, of the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.
“This region is primarily made up of rural areas, with persistent poverty levels that are at least 20%, which is higher than the national average.”
In 2007, the CDC’s National Program of Cancer Registries (NPCR) published a comprehensive evaluation of cancer incidence rates in Appalachia between 2001 and 2003.
The data showed higher cancer rates in Appalachia than in the rest of the US. However, this publication had some shortcomings, including data that were not available for analysis.
“The current analyses reported here were performed to update the earlier evaluation by expanding the diagnosis years from 2004 to 2011 and including data on 100% of the Appalachian and non-Appalachian populations,” Wilson said.
For this study, Wilson and her colleagues used data from the NPCR and the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Together, NPCR and SEER cover 100% of the US population.
The researchers analyzed the Appalachian population by region (north, central, and south Appalachia), gender, race (black and white only), and Appalachian Regional Commission-designated economic status (distressed, at-risk, transitional, competitive, and attainment). And the team compared these data with data on the non-Appalachian population.
The results showed that cancer incidence rates (IRs) were elevated among Appalachians regardless of how they were categorized. The IRs were per 100,000 people, age-adjusted to the 2000 US standard population.
The IR for all cancers was 565.8 for males in Appalachia and 543.0 for non-Appalachian males (P<0.05). And the cancer IRs for females were 428.7 in Appalachia and 418.2 outside the region (P<0.05).
There was no significant difference between the regions in IRs for lymphomas. The Hodgkin lymphoma IRs were 3.1 in Appalachian males, 3.2 in non-Appalachian males, and 2.5 for females in both regions.
The non-Hodgkin lymphoma IRs were 23.3 in Appalachian males, 23.4 in non-Appalachian males, 16.4 in Appalachian females, and 16.3 in non-Appalachian females.
Myeloma IRs were significantly lower in Appalachia (P<0.05). The myeloma IRs were 7.3 in Appalachian males, 7.5 in non-Appalachian males, 4.7 in Appalachian females, and 4.9 in non-Appalachian females.
There was no significant difference in leukemia IRs among males, but females in Appalachia had a significantly higher leukemia IR (P<0.05). The leukemia IRs were 16.9 in Appalachian males, 16.7 in non-Appalachian males, 10.4 in Appalachian females, and 10.2 in non-Appalachian females.
“Appalachia continues to have higher cancer incidence rates than the rest of the country,” Wilson said. “But a promising finding is that we’re seeing the gap narrow in the incidence rates between Appalachia and non-Appalachia since the 2007 analysis, with the exception of cancers of the oral cavity and pharynx, larynx, lung and bronchus, and thyroid.”
“This study helps identify types of cancer in the Appalachian region that could be reduced through more evidence-based screening and detection. Our study also emphasizes the importance of lifestyle changes needed to prevent and reduce cancer burden.”
The researchers noted that this study did not differentiate urban versus rural areas within each county, and data on screening and risk factors were based on self-reported responses.
Furthermore, cancer IRs were calculated for all ages combined and were not evaluated by age groups. Future analyses will be targeted toward capturing these finer details, Wilson said.
NICE recommends panobinostat for multiple myeloma
Photo courtesy of Novartis
The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.
In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.
NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.
NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.
Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.
The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.
Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each.
Photo courtesy of Novartis
The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.
In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.
NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.
NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.
Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.
The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.
Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each.
Photo courtesy of Novartis
The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending panobinostat (Farydak) be made available on the National Health Service.
In the European Union, panobinostat is approved for use in combination with bortezomib and dexamethasone to treat adults with relapsed and/or refractory multiple myeloma who have received at least 2 prior treatment regimens, including bortezomib and an immunomodulatory agent.
NICE’s recommendation of panobinostat is contingent upon the drug being provided with the discount agreed upon in the patient access scheme.
NICE previously issued a guidance in which it did not recommend panobinostat, but the drug’s manufacturer, Novartis, submitted a revised economic analysis that allowed NICE to recommend the drug.
Novartis has agreed to a patient access scheme with the Department of Health. This scheme provides a discount to the list price of panobinostat, with the discount applied at the point of purchase or invoice.
The level of the discount is commercial in confidence, but the Department of Health said this patient access scheme does not constitute an excessive administrative burden on the National Health Service.
Panobinostat costs £776 per 20 mg tablet. The recommended starting dose is 20 mg, taken orally once a day, on days 1, 3, 5, 8, 10, and 12 of a 21-day cycle. Patients should receive panobinostat for 8 cycles. If they show clinical benefit, they should continue the treatment for 4 additional cycles of 6 weeks each.
FDA expands approved use of MM drug
Photo courtesy of Amgen
The US Food and Drug Administration (FDA) has approved the use of carfilzomib (Kyprolis) in combination with dexamethasone or lenalidomide plus dexamethasone to treat patients with relapsed or refractory multiple myeloma (MM) who have received 1 to 3 prior lines of therapy.
The FDA also approved use of carfilzomib as a single agent to treat patients with relapsed or refractory MM who have received 1 or more lines of therapy.
This decision converts to full approval the initial accelerated approval granted for single-agent carfilzomib in July 2012.
In July 2015, the FDA approved the use of carfilzomib in combination with lenalidomide and dexamethasone for the treatment of patients with relapsed MM who have received 1 to 3 prior lines of therapy.
The latest approval of carfilzomib is based on results from the phase 3 ENDEAVOR study.
Trial results
The ENDEAVOR trial included 929 MM patients whose disease had relapsed after 1 to 3 prior therapeutic regimens. The patients received either carfilzomib plus dexamethasone (n=464) or bortezomib plus dexamethasone (n=465) until disease progression.
The primary endpoint was progression-free survival. The median was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm. The hazard ratio was 0.53 (P<0.0001).
Overall survival data are not yet mature and continue to be monitored.
Treatment discontinuation due to adverse events and on-study deaths were comparable between the 2 treatment arms.
However, a number of known adverse events were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).
Carfilzomib is marketed as Kyprolis by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, with the exception of Japan. For more information on the drug, visit www.kyprolis.com.
Photo courtesy of Amgen
The US Food and Drug Administration (FDA) has approved the use of carfilzomib (Kyprolis) in combination with dexamethasone or lenalidomide plus dexamethasone to treat patients with relapsed or refractory multiple myeloma (MM) who have received 1 to 3 prior lines of therapy.
The FDA also approved use of carfilzomib as a single agent to treat patients with relapsed or refractory MM who have received 1 or more lines of therapy.
This decision converts to full approval the initial accelerated approval granted for single-agent carfilzomib in July 2012.
In July 2015, the FDA approved the use of carfilzomib in combination with lenalidomide and dexamethasone for the treatment of patients with relapsed MM who have received 1 to 3 prior lines of therapy.
The latest approval of carfilzomib is based on results from the phase 3 ENDEAVOR study.
Trial results
The ENDEAVOR trial included 929 MM patients whose disease had relapsed after 1 to 3 prior therapeutic regimens. The patients received either carfilzomib plus dexamethasone (n=464) or bortezomib plus dexamethasone (n=465) until disease progression.
The primary endpoint was progression-free survival. The median was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm. The hazard ratio was 0.53 (P<0.0001).
Overall survival data are not yet mature and continue to be monitored.
Treatment discontinuation due to adverse events and on-study deaths were comparable between the 2 treatment arms.
However, a number of known adverse events were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).
Carfilzomib is marketed as Kyprolis by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, with the exception of Japan. For more information on the drug, visit www.kyprolis.com.
Photo courtesy of Amgen
The US Food and Drug Administration (FDA) has approved the use of carfilzomib (Kyprolis) in combination with dexamethasone or lenalidomide plus dexamethasone to treat patients with relapsed or refractory multiple myeloma (MM) who have received 1 to 3 prior lines of therapy.
The FDA also approved use of carfilzomib as a single agent to treat patients with relapsed or refractory MM who have received 1 or more lines of therapy.
This decision converts to full approval the initial accelerated approval granted for single-agent carfilzomib in July 2012.
In July 2015, the FDA approved the use of carfilzomib in combination with lenalidomide and dexamethasone for the treatment of patients with relapsed MM who have received 1 to 3 prior lines of therapy.
The latest approval of carfilzomib is based on results from the phase 3 ENDEAVOR study.
Trial results
The ENDEAVOR trial included 929 MM patients whose disease had relapsed after 1 to 3 prior therapeutic regimens. The patients received either carfilzomib plus dexamethasone (n=464) or bortezomib plus dexamethasone (n=465) until disease progression.
The primary endpoint was progression-free survival. The median was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm. The hazard ratio was 0.53 (P<0.0001).
Overall survival data are not yet mature and continue to be monitored.
Treatment discontinuation due to adverse events and on-study deaths were comparable between the 2 treatment arms.
However, a number of known adverse events were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).
Carfilzomib is marketed as Kyprolis by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, with the exception of Japan. For more information on the drug, visit www.kyprolis.com.
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.
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.
Making sense of the expanded myeloma treatment landscape
ORLANDO – The moment the Food and Drug Administration approved daratumumab, ixazomib, and elotuzumab in rapid-fire succession over 15 days in November 2015, Dr. S. Vincent Rajkumar’s phone started ringing.
As with other multiple myeloma experts, three common questions kept cropping up:
• For previously untreated patients, should we add bortezomib to lenalidomide plus dexamethasone (Rd) based on the S0777 results?
• For previously treated patients, should we add ixazomib or elotuzumab to Rd?
• Should we add daratumumab to frontline therapy right out of the box?
Daratumumab (Darzalex), ixazomib (Ninlaro), and elotuzumab (Empliciti) are welcome additions to the armamentarium, but the problem with this plethora of riches is that numerous treatments already exist for frontline multiple myeloma, observed Dr. Rajkumar, professor of medicine at the Mayo Clinic in Rochester, Minn.
In fact, the National Comprehensive Cancer Network guidelines list 22 possible newly diagnosed myeloma regimens that can be potentially recommended for patients.
“This definitely leads to confusion in the community. And this was the result of the fact that we didn’t have a single, good randomized trial with a survival benefit of a modern therapy against another modern therapy,” Dr. Rajkumar said at the annual meeting of the American Society of Hematology during a joint FDA/ASH symposium on the three newly approved agents.
This quandary was solved at ASH with phase III randomized data from the Southwest Oncology Group S0777 study showing a significant overall survival advantage with a triplet of bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) followed by continuous Rd maintenance compared with Rd alone and ongoing maintenance in untreated patients who did not intend to receive stem cell transplant, he said.
Median overall survival was 75 months for the triplet vs. 64 months for the Rd doublet (hazard ratio, 0.709; two-sided log-rank P = .0250), and median PFS 43 months vs. 30 months (HR, 0.712; one-sided P = .0018), study author Dr. Brian Durie, of Cedars-Sinai Comprehensive Cancer Center in Los Angeles, reported (Abstract 25).
The VRd triplet is already in use in the United States, but based on the S0777 results, many groups, including the Mayo Clinic, have changed treatment guidelines and now “prefer bortezomib, len-dex for frontline therapy, not just in transplant candidates, but also in non-transplant candidates,” Dr. Rajkumar said.
In countries where VRd is not possible, bortezomib, thalidomide, and dexamethasone (VTd) is a second option.
Rd is an appropriate therapy for non-transplant candidates who are frail or aged 75 years or older, he said, adding that there is no need to add bortezomib for patients already on Rd and doing well.
“If your patient is doing well on a doublet, leave them alone,” Dr. Rajkumar advised.
Similarly, for patients with relapsed myeloma who are doing well on Rd, there isn’t “an urgent need” to add ixazomib or elotuzumab, but rather, he said, “We can reserve those for when the patient progresses.”
Ixazomib is approved in combination with Rd after at least one prior therapy, but the oral proteasome inhibitor may have a role in the frontline treatment of standard-risk patients. It is a very simple regimen, just three pills a month, and “the side effect profile is outstanding; virtually difficult to tell who’s taking placebo and who’s taking drug,” Dr. Rajkumar observed.
In addition, some patients may not have access to bortezomib because of insurance reasons or can’t drive to the clinic once a week to get the shot, while others may be too frail to get an intravenous or subcutaneous shot or may have neuropathy.
“For whatever reason, I think it is reasonable to keep in mind that we may have a situation where we can use ixazomib/len-dex in clinical practice if the patient’s best interests so dictate,” he said.
For high-risk patients (deletion 17p or translocations t(4;14), t(14;16), t(14;20), VRd or VTd are obvious upfront choices. Based on four phase II trials and the ASPIRE results in the relapsed and refractory setting, however, the Mayo Clinic has already decided that the recently approved second-generation proteasome inhibitor carfilzomib (Kyprolis) plus Rd is also worth considering.
Adding a monoclonal antibody such as elotuzumab or daratumumab to a VRd triplet or ixazomib, lenalidomide, and dexamethasone (IRd) triplet may be another way to improve outcomes in high-risk patients, who still die with a median overall survival of 3 years, Dr. Rajkumar said. This strategy is already being used in the ongoing SWOG S1211 study.
For maintenance therapy after VRd or VTd and autologous stem cell transplant, he recommended lenalidomide for standard-risk patients and bortezomib-based maintenance for high-risk patients, but said ixazomib-based maintenance with the addition of monoclonal antibodies may also have a role in high-risk patients.
What may be more important going forward is how these three drugs will be used in clinical trials, Dr. Rajkumar observed.
“We’d rather put all patients on clinical trials than any of the recommendations I made,” he said. “The problem is that clinical trials have to be appropriately designed.”
Several phase III trials are already ongoing comparing a doublet versus a triplet (IRd vs. Rd, elotuzumab-Rd vs. Rd, and daratumumab-Rd vs. Rd) in the frontline setting, so the key question for future trials is which triplet: VRd, KRd, elotuzumab-Rd, or daratumumab-Rd, and to what endpoint.
Progression-free survival can remain a primary endpoint for comparing two triplets in the frontline, but PFS alone is not enough in the maintenance setting and investigators should look to other primary endpoints such as PFS2, PFS1 vs. PFS2, overall survival with a higher type 1 error than currently used, or PFS plus validated patient-reported or quality of life outcomes, Dr. Rajkumar said.
Relapsed/refractory disease
Speaking on how the three new agents fit into the relapsed or refractory space,Dr. Paul Richardson, of Dana-Farber Cancer Institute, Boston, said three-drug platforms are emerging as a standard of care for relapsed or refractory disease after studies have shown time and time again they are better than doublets.
He highlighted phase III data reported at ASH by Dr. Philippe Moreau from TOURMALINE-MM1 (Abstract 727) showing a 35% improvement in PFS with weekly oral ixazomib plus lenalidomide-dexamethasone vs. Rd alone in relapsed and/or refractory multiple myeloma.
This translated into a median 6-month gain in PFS compared with an almost 9-month PFS benefit seen in ASPIRE with carfilzomib plus Rd, but cross-trial comparisons should be approached with some caution and both hazard ratios were very robust, he said. In addition, as previously observed, ixazomib is remarkably well tolerated.
“I think ixazomib, particularly in older patients and particularly in patients with high-risk disease, will be very useful in the context of the three-drug or even greater combinations. So there’s a strong rationale for its use,” Dr. Richardson said.
He went on to say that elotuzumab has shown remarkable anti-myeloma activity in the relapsed and refractory setting, improving both the overall response rate and PFS when used in combination with Ld vs. Ld alone in the ELOQUENT-2 trial. Updated results from ELOQUENT-2 were presented at the ASH meeting (Abstract 28).
A PFS benefit was also seen when elotuzumab was added to bortezomib and dexamethasone, with a 24% reduction in the risk of disease progression or death reported in a study presented at ASH by myeloma expert Dr. Antonio Palumbo (Abstract 510).
“My point in showing this is that when you think of elotuzumab being used with lenalidomide and dexamethasone in relapse, many of our patients are actually on them as maintenance when it occurs, therefore elotuzumab may have a role in combination, for example, with proteasome inhibitors in this same setting,” Dr. Richardson said.
Several pomalidomide-based triple therapy combinations have been evaluated in advanced relapsed or refractory myeloma, with a phase II study (Abstract 506) reported that morning at ASH showing the third-generation immunomodulatory drug (IMiD) pomalidomide induced responses in 60% of heavily pretreated patients when partnered with pembrolizumab and dexamethasone.
Combination strategies with daratumumab are also very provocative, particularly in the context of IMiDs, he noted. A phase Ib study reported in the same early morning session by Dr. Ajai Chari (Abstract 508) had a “very encouraging” overall response rate of 71% with daratumumab plus pomalidomide and dexamethasone in heavily pretreated patients, including 43% very good partial responses or better, and an overall response rate of 67% among double-refractory patients.
“Daratumumab and elotuzumab, in my view, as first-in-class monoclonal antibodies, are paradigm-changing agents,” Dr. Richardson concluded. “They provide us with this mutation-driven ability to overdrive the impact of those mutations and the important point is that they prescribe an entirely non-crossresistant strategy that can be easily added to existing platforms of drugs.”
Dr. Rajkumar reported discussion of off-label drug use for elotuzumab, daratumumab, ixazomib, and carfilzomib in untreated myeloma, maintenance, and early relapse. Dr. Richardson reported membership on a board of directors or advisory committee for Millennium Takeda, Celgene, Janssen, Bristol-Myers Squibb, and Novartis, and research funding from Millennium Takeda and Celgene.
ORLANDO – The moment the Food and Drug Administration approved daratumumab, ixazomib, and elotuzumab in rapid-fire succession over 15 days in November 2015, Dr. S. Vincent Rajkumar’s phone started ringing.
As with other multiple myeloma experts, three common questions kept cropping up:
• For previously untreated patients, should we add bortezomib to lenalidomide plus dexamethasone (Rd) based on the S0777 results?
• For previously treated patients, should we add ixazomib or elotuzumab to Rd?
• Should we add daratumumab to frontline therapy right out of the box?
Daratumumab (Darzalex), ixazomib (Ninlaro), and elotuzumab (Empliciti) are welcome additions to the armamentarium, but the problem with this plethora of riches is that numerous treatments already exist for frontline multiple myeloma, observed Dr. Rajkumar, professor of medicine at the Mayo Clinic in Rochester, Minn.
In fact, the National Comprehensive Cancer Network guidelines list 22 possible newly diagnosed myeloma regimens that can be potentially recommended for patients.
“This definitely leads to confusion in the community. And this was the result of the fact that we didn’t have a single, good randomized trial with a survival benefit of a modern therapy against another modern therapy,” Dr. Rajkumar said at the annual meeting of the American Society of Hematology during a joint FDA/ASH symposium on the three newly approved agents.
This quandary was solved at ASH with phase III randomized data from the Southwest Oncology Group S0777 study showing a significant overall survival advantage with a triplet of bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) followed by continuous Rd maintenance compared with Rd alone and ongoing maintenance in untreated patients who did not intend to receive stem cell transplant, he said.
Median overall survival was 75 months for the triplet vs. 64 months for the Rd doublet (hazard ratio, 0.709; two-sided log-rank P = .0250), and median PFS 43 months vs. 30 months (HR, 0.712; one-sided P = .0018), study author Dr. Brian Durie, of Cedars-Sinai Comprehensive Cancer Center in Los Angeles, reported (Abstract 25).
The VRd triplet is already in use in the United States, but based on the S0777 results, many groups, including the Mayo Clinic, have changed treatment guidelines and now “prefer bortezomib, len-dex for frontline therapy, not just in transplant candidates, but also in non-transplant candidates,” Dr. Rajkumar said.
In countries where VRd is not possible, bortezomib, thalidomide, and dexamethasone (VTd) is a second option.
Rd is an appropriate therapy for non-transplant candidates who are frail or aged 75 years or older, he said, adding that there is no need to add bortezomib for patients already on Rd and doing well.
“If your patient is doing well on a doublet, leave them alone,” Dr. Rajkumar advised.
Similarly, for patients with relapsed myeloma who are doing well on Rd, there isn’t “an urgent need” to add ixazomib or elotuzumab, but rather, he said, “We can reserve those for when the patient progresses.”
Ixazomib is approved in combination with Rd after at least one prior therapy, but the oral proteasome inhibitor may have a role in the frontline treatment of standard-risk patients. It is a very simple regimen, just three pills a month, and “the side effect profile is outstanding; virtually difficult to tell who’s taking placebo and who’s taking drug,” Dr. Rajkumar observed.
In addition, some patients may not have access to bortezomib because of insurance reasons or can’t drive to the clinic once a week to get the shot, while others may be too frail to get an intravenous or subcutaneous shot or may have neuropathy.
“For whatever reason, I think it is reasonable to keep in mind that we may have a situation where we can use ixazomib/len-dex in clinical practice if the patient’s best interests so dictate,” he said.
For high-risk patients (deletion 17p or translocations t(4;14), t(14;16), t(14;20), VRd or VTd are obvious upfront choices. Based on four phase II trials and the ASPIRE results in the relapsed and refractory setting, however, the Mayo Clinic has already decided that the recently approved second-generation proteasome inhibitor carfilzomib (Kyprolis) plus Rd is also worth considering.
Adding a monoclonal antibody such as elotuzumab or daratumumab to a VRd triplet or ixazomib, lenalidomide, and dexamethasone (IRd) triplet may be another way to improve outcomes in high-risk patients, who still die with a median overall survival of 3 years, Dr. Rajkumar said. This strategy is already being used in the ongoing SWOG S1211 study.
For maintenance therapy after VRd or VTd and autologous stem cell transplant, he recommended lenalidomide for standard-risk patients and bortezomib-based maintenance for high-risk patients, but said ixazomib-based maintenance with the addition of monoclonal antibodies may also have a role in high-risk patients.
What may be more important going forward is how these three drugs will be used in clinical trials, Dr. Rajkumar observed.
“We’d rather put all patients on clinical trials than any of the recommendations I made,” he said. “The problem is that clinical trials have to be appropriately designed.”
Several phase III trials are already ongoing comparing a doublet versus a triplet (IRd vs. Rd, elotuzumab-Rd vs. Rd, and daratumumab-Rd vs. Rd) in the frontline setting, so the key question for future trials is which triplet: VRd, KRd, elotuzumab-Rd, or daratumumab-Rd, and to what endpoint.
Progression-free survival can remain a primary endpoint for comparing two triplets in the frontline, but PFS alone is not enough in the maintenance setting and investigators should look to other primary endpoints such as PFS2, PFS1 vs. PFS2, overall survival with a higher type 1 error than currently used, or PFS plus validated patient-reported or quality of life outcomes, Dr. Rajkumar said.
Relapsed/refractory disease
Speaking on how the three new agents fit into the relapsed or refractory space,Dr. Paul Richardson, of Dana-Farber Cancer Institute, Boston, said three-drug platforms are emerging as a standard of care for relapsed or refractory disease after studies have shown time and time again they are better than doublets.
He highlighted phase III data reported at ASH by Dr. Philippe Moreau from TOURMALINE-MM1 (Abstract 727) showing a 35% improvement in PFS with weekly oral ixazomib plus lenalidomide-dexamethasone vs. Rd alone in relapsed and/or refractory multiple myeloma.
This translated into a median 6-month gain in PFS compared with an almost 9-month PFS benefit seen in ASPIRE with carfilzomib plus Rd, but cross-trial comparisons should be approached with some caution and both hazard ratios were very robust, he said. In addition, as previously observed, ixazomib is remarkably well tolerated.
“I think ixazomib, particularly in older patients and particularly in patients with high-risk disease, will be very useful in the context of the three-drug or even greater combinations. So there’s a strong rationale for its use,” Dr. Richardson said.
He went on to say that elotuzumab has shown remarkable anti-myeloma activity in the relapsed and refractory setting, improving both the overall response rate and PFS when used in combination with Ld vs. Ld alone in the ELOQUENT-2 trial. Updated results from ELOQUENT-2 were presented at the ASH meeting (Abstract 28).
A PFS benefit was also seen when elotuzumab was added to bortezomib and dexamethasone, with a 24% reduction in the risk of disease progression or death reported in a study presented at ASH by myeloma expert Dr. Antonio Palumbo (Abstract 510).
“My point in showing this is that when you think of elotuzumab being used with lenalidomide and dexamethasone in relapse, many of our patients are actually on them as maintenance when it occurs, therefore elotuzumab may have a role in combination, for example, with proteasome inhibitors in this same setting,” Dr. Richardson said.
Several pomalidomide-based triple therapy combinations have been evaluated in advanced relapsed or refractory myeloma, with a phase II study (Abstract 506) reported that morning at ASH showing the third-generation immunomodulatory drug (IMiD) pomalidomide induced responses in 60% of heavily pretreated patients when partnered with pembrolizumab and dexamethasone.
Combination strategies with daratumumab are also very provocative, particularly in the context of IMiDs, he noted. A phase Ib study reported in the same early morning session by Dr. Ajai Chari (Abstract 508) had a “very encouraging” overall response rate of 71% with daratumumab plus pomalidomide and dexamethasone in heavily pretreated patients, including 43% very good partial responses or better, and an overall response rate of 67% among double-refractory patients.
“Daratumumab and elotuzumab, in my view, as first-in-class monoclonal antibodies, are paradigm-changing agents,” Dr. Richardson concluded. “They provide us with this mutation-driven ability to overdrive the impact of those mutations and the important point is that they prescribe an entirely non-crossresistant strategy that can be easily added to existing platforms of drugs.”
Dr. Rajkumar reported discussion of off-label drug use for elotuzumab, daratumumab, ixazomib, and carfilzomib in untreated myeloma, maintenance, and early relapse. Dr. Richardson reported membership on a board of directors or advisory committee for Millennium Takeda, Celgene, Janssen, Bristol-Myers Squibb, and Novartis, and research funding from Millennium Takeda and Celgene.
ORLANDO – The moment the Food and Drug Administration approved daratumumab, ixazomib, and elotuzumab in rapid-fire succession over 15 days in November 2015, Dr. S. Vincent Rajkumar’s phone started ringing.
As with other multiple myeloma experts, three common questions kept cropping up:
• For previously untreated patients, should we add bortezomib to lenalidomide plus dexamethasone (Rd) based on the S0777 results?
• For previously treated patients, should we add ixazomib or elotuzumab to Rd?
• Should we add daratumumab to frontline therapy right out of the box?
Daratumumab (Darzalex), ixazomib (Ninlaro), and elotuzumab (Empliciti) are welcome additions to the armamentarium, but the problem with this plethora of riches is that numerous treatments already exist for frontline multiple myeloma, observed Dr. Rajkumar, professor of medicine at the Mayo Clinic in Rochester, Minn.
In fact, the National Comprehensive Cancer Network guidelines list 22 possible newly diagnosed myeloma regimens that can be potentially recommended for patients.
“This definitely leads to confusion in the community. And this was the result of the fact that we didn’t have a single, good randomized trial with a survival benefit of a modern therapy against another modern therapy,” Dr. Rajkumar said at the annual meeting of the American Society of Hematology during a joint FDA/ASH symposium on the three newly approved agents.
This quandary was solved at ASH with phase III randomized data from the Southwest Oncology Group S0777 study showing a significant overall survival advantage with a triplet of bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) followed by continuous Rd maintenance compared with Rd alone and ongoing maintenance in untreated patients who did not intend to receive stem cell transplant, he said.
Median overall survival was 75 months for the triplet vs. 64 months for the Rd doublet (hazard ratio, 0.709; two-sided log-rank P = .0250), and median PFS 43 months vs. 30 months (HR, 0.712; one-sided P = .0018), study author Dr. Brian Durie, of Cedars-Sinai Comprehensive Cancer Center in Los Angeles, reported (Abstract 25).
The VRd triplet is already in use in the United States, but based on the S0777 results, many groups, including the Mayo Clinic, have changed treatment guidelines and now “prefer bortezomib, len-dex for frontline therapy, not just in transplant candidates, but also in non-transplant candidates,” Dr. Rajkumar said.
In countries where VRd is not possible, bortezomib, thalidomide, and dexamethasone (VTd) is a second option.
Rd is an appropriate therapy for non-transplant candidates who are frail or aged 75 years or older, he said, adding that there is no need to add bortezomib for patients already on Rd and doing well.
“If your patient is doing well on a doublet, leave them alone,” Dr. Rajkumar advised.
Similarly, for patients with relapsed myeloma who are doing well on Rd, there isn’t “an urgent need” to add ixazomib or elotuzumab, but rather, he said, “We can reserve those for when the patient progresses.”
Ixazomib is approved in combination with Rd after at least one prior therapy, but the oral proteasome inhibitor may have a role in the frontline treatment of standard-risk patients. It is a very simple regimen, just three pills a month, and “the side effect profile is outstanding; virtually difficult to tell who’s taking placebo and who’s taking drug,” Dr. Rajkumar observed.
In addition, some patients may not have access to bortezomib because of insurance reasons or can’t drive to the clinic once a week to get the shot, while others may be too frail to get an intravenous or subcutaneous shot or may have neuropathy.
“For whatever reason, I think it is reasonable to keep in mind that we may have a situation where we can use ixazomib/len-dex in clinical practice if the patient’s best interests so dictate,” he said.
For high-risk patients (deletion 17p or translocations t(4;14), t(14;16), t(14;20), VRd or VTd are obvious upfront choices. Based on four phase II trials and the ASPIRE results in the relapsed and refractory setting, however, the Mayo Clinic has already decided that the recently approved second-generation proteasome inhibitor carfilzomib (Kyprolis) plus Rd is also worth considering.
Adding a monoclonal antibody such as elotuzumab or daratumumab to a VRd triplet or ixazomib, lenalidomide, and dexamethasone (IRd) triplet may be another way to improve outcomes in high-risk patients, who still die with a median overall survival of 3 years, Dr. Rajkumar said. This strategy is already being used in the ongoing SWOG S1211 study.
For maintenance therapy after VRd or VTd and autologous stem cell transplant, he recommended lenalidomide for standard-risk patients and bortezomib-based maintenance for high-risk patients, but said ixazomib-based maintenance with the addition of monoclonal antibodies may also have a role in high-risk patients.
What may be more important going forward is how these three drugs will be used in clinical trials, Dr. Rajkumar observed.
“We’d rather put all patients on clinical trials than any of the recommendations I made,” he said. “The problem is that clinical trials have to be appropriately designed.”
Several phase III trials are already ongoing comparing a doublet versus a triplet (IRd vs. Rd, elotuzumab-Rd vs. Rd, and daratumumab-Rd vs. Rd) in the frontline setting, so the key question for future trials is which triplet: VRd, KRd, elotuzumab-Rd, or daratumumab-Rd, and to what endpoint.
Progression-free survival can remain a primary endpoint for comparing two triplets in the frontline, but PFS alone is not enough in the maintenance setting and investigators should look to other primary endpoints such as PFS2, PFS1 vs. PFS2, overall survival with a higher type 1 error than currently used, or PFS plus validated patient-reported or quality of life outcomes, Dr. Rajkumar said.
Relapsed/refractory disease
Speaking on how the three new agents fit into the relapsed or refractory space,Dr. Paul Richardson, of Dana-Farber Cancer Institute, Boston, said three-drug platforms are emerging as a standard of care for relapsed or refractory disease after studies have shown time and time again they are better than doublets.
He highlighted phase III data reported at ASH by Dr. Philippe Moreau from TOURMALINE-MM1 (Abstract 727) showing a 35% improvement in PFS with weekly oral ixazomib plus lenalidomide-dexamethasone vs. Rd alone in relapsed and/or refractory multiple myeloma.
This translated into a median 6-month gain in PFS compared with an almost 9-month PFS benefit seen in ASPIRE with carfilzomib plus Rd, but cross-trial comparisons should be approached with some caution and both hazard ratios were very robust, he said. In addition, as previously observed, ixazomib is remarkably well tolerated.
“I think ixazomib, particularly in older patients and particularly in patients with high-risk disease, will be very useful in the context of the three-drug or even greater combinations. So there’s a strong rationale for its use,” Dr. Richardson said.
He went on to say that elotuzumab has shown remarkable anti-myeloma activity in the relapsed and refractory setting, improving both the overall response rate and PFS when used in combination with Ld vs. Ld alone in the ELOQUENT-2 trial. Updated results from ELOQUENT-2 were presented at the ASH meeting (Abstract 28).
A PFS benefit was also seen when elotuzumab was added to bortezomib and dexamethasone, with a 24% reduction in the risk of disease progression or death reported in a study presented at ASH by myeloma expert Dr. Antonio Palumbo (Abstract 510).
“My point in showing this is that when you think of elotuzumab being used with lenalidomide and dexamethasone in relapse, many of our patients are actually on them as maintenance when it occurs, therefore elotuzumab may have a role in combination, for example, with proteasome inhibitors in this same setting,” Dr. Richardson said.
Several pomalidomide-based triple therapy combinations have been evaluated in advanced relapsed or refractory myeloma, with a phase II study (Abstract 506) reported that morning at ASH showing the third-generation immunomodulatory drug (IMiD) pomalidomide induced responses in 60% of heavily pretreated patients when partnered with pembrolizumab and dexamethasone.
Combination strategies with daratumumab are also very provocative, particularly in the context of IMiDs, he noted. A phase Ib study reported in the same early morning session by Dr. Ajai Chari (Abstract 508) had a “very encouraging” overall response rate of 71% with daratumumab plus pomalidomide and dexamethasone in heavily pretreated patients, including 43% very good partial responses or better, and an overall response rate of 67% among double-refractory patients.
“Daratumumab and elotuzumab, in my view, as first-in-class monoclonal antibodies, are paradigm-changing agents,” Dr. Richardson concluded. “They provide us with this mutation-driven ability to overdrive the impact of those mutations and the important point is that they prescribe an entirely non-crossresistant strategy that can be easily added to existing platforms of drugs.”
Dr. Rajkumar reported discussion of off-label drug use for elotuzumab, daratumumab, ixazomib, and carfilzomib in untreated myeloma, maintenance, and early relapse. Dr. Richardson reported membership on a board of directors or advisory committee for Millennium Takeda, Celgene, Janssen, Bristol-Myers Squibb, and Novartis, and research funding from Millennium Takeda and Celgene.
EXPERT ANALYSIS FROM ASH 2015
Daratumumab clinically active, well tolerated in heavily treated multiple myeloma
In patients with multiple myeloma who were treated with at least three prior therapies (median five), daratumumab demonstrated substantial clinical activity and was well tolerated, investigators reported in the Lancet.
Overall response rates were observed in 31 of 106 people (ORR 29.2%; 95% confidence interval, 20.8-38.9), stringent complete responses in 3, and very good partial responses in 10 people. In total, 87 patients (82%) had received more than three lines of therapy: all patients had been treated previously with proteasome inhibitors and immunomodulatory drugs, and dexamethasone. In addition, 103 (97%) were refractory to the last line of therapy before study enrollment, and 95% were refractory to the most recent proteasome inhibitors and immunomodulatory drugs.
“Resistance to any previous therapy had no effect on the activity of daratumumab, lending support to a novel mechanism of action, but these findings need to be confirmed in larger studies,” wrote Dr. Sagar Lonial, executive vice chair of the department of hematology medical oncology, Emory University, Atlanta, and colleagues (Lancet. 2016 Jan 7. doi: 10.1016/S0140-6736[15]01120-4).
Daratumumab was well tolerated. The most common hematologic treatment-emergent adverse events of any grade were anemia (33%), thrombocytopenia (25%), and neutropenia (23%). The overall favorable safety profile makes it a promising candidate for combination regimens, and the monoclonal IgG1 antibody has shown early activity in combination with lenalidomide and dexamethasone, according to the researchers.
The open-label, multicenter, phase II trial included 106 patients who received daratumumab 16 mg/kg. The median time since initial diagnosis was 4.8 years (1.1-23.8 years), median number of previous therapies was 5 (2-14), and 80% of patients had received autologous stem cell transplantation.
In patients with multiple myeloma who were treated with at least three prior therapies (median five), daratumumab demonstrated substantial clinical activity and was well tolerated, investigators reported in the Lancet.
Overall response rates were observed in 31 of 106 people (ORR 29.2%; 95% confidence interval, 20.8-38.9), stringent complete responses in 3, and very good partial responses in 10 people. In total, 87 patients (82%) had received more than three lines of therapy: all patients had been treated previously with proteasome inhibitors and immunomodulatory drugs, and dexamethasone. In addition, 103 (97%) were refractory to the last line of therapy before study enrollment, and 95% were refractory to the most recent proteasome inhibitors and immunomodulatory drugs.
“Resistance to any previous therapy had no effect on the activity of daratumumab, lending support to a novel mechanism of action, but these findings need to be confirmed in larger studies,” wrote Dr. Sagar Lonial, executive vice chair of the department of hematology medical oncology, Emory University, Atlanta, and colleagues (Lancet. 2016 Jan 7. doi: 10.1016/S0140-6736[15]01120-4).
Daratumumab was well tolerated. The most common hematologic treatment-emergent adverse events of any grade were anemia (33%), thrombocytopenia (25%), and neutropenia (23%). The overall favorable safety profile makes it a promising candidate for combination regimens, and the monoclonal IgG1 antibody has shown early activity in combination with lenalidomide and dexamethasone, according to the researchers.
The open-label, multicenter, phase II trial included 106 patients who received daratumumab 16 mg/kg. The median time since initial diagnosis was 4.8 years (1.1-23.8 years), median number of previous therapies was 5 (2-14), and 80% of patients had received autologous stem cell transplantation.
In patients with multiple myeloma who were treated with at least three prior therapies (median five), daratumumab demonstrated substantial clinical activity and was well tolerated, investigators reported in the Lancet.
Overall response rates were observed in 31 of 106 people (ORR 29.2%; 95% confidence interval, 20.8-38.9), stringent complete responses in 3, and very good partial responses in 10 people. In total, 87 patients (82%) had received more than three lines of therapy: all patients had been treated previously with proteasome inhibitors and immunomodulatory drugs, and dexamethasone. In addition, 103 (97%) were refractory to the last line of therapy before study enrollment, and 95% were refractory to the most recent proteasome inhibitors and immunomodulatory drugs.
“Resistance to any previous therapy had no effect on the activity of daratumumab, lending support to a novel mechanism of action, but these findings need to be confirmed in larger studies,” wrote Dr. Sagar Lonial, executive vice chair of the department of hematology medical oncology, Emory University, Atlanta, and colleagues (Lancet. 2016 Jan 7. doi: 10.1016/S0140-6736[15]01120-4).
Daratumumab was well tolerated. The most common hematologic treatment-emergent adverse events of any grade were anemia (33%), thrombocytopenia (25%), and neutropenia (23%). The overall favorable safety profile makes it a promising candidate for combination regimens, and the monoclonal IgG1 antibody has shown early activity in combination with lenalidomide and dexamethasone, according to the researchers.
The open-label, multicenter, phase II trial included 106 patients who received daratumumab 16 mg/kg. The median time since initial diagnosis was 4.8 years (1.1-23.8 years), median number of previous therapies was 5 (2-14), and 80% of patients had received autologous stem cell transplantation.
FROM THE LANCET
Key clinical point: Daratumumab monotherapy was clinically active and well tolerated in patients with multiple myeloma who were treated with at least three prior therapies.
Major finding: In the 16 mg/kg group, 31 of 106 patients achieved an overall response rate (ORR 29.2%; 95% confidence interval, 20.8-38.9); 3 achieved a stringent complete response; 10 achieved a very good partial response.
Data source: The open-label, multicenter, phase II trial included 106 patients who received daratumumab 16 mg/kg.
Disclosures: Janssen Research & Development contributed to the design of the study. Dr. Lonial reported ties Bristol-Myers Squibb, Celgene, Janssen, Millennium, Novartis, and Onyx. Several of his coauthors reported ties to industry.
US cancer stats: The good and the bad
patient and her father
Photo by Rhoda Baer
The American Cancer Society’s 2016 report on cancer in the US suggests that, in recent years, overall trends in cancer incidence have remained stable for women and declined for men.
However, the rates of certain malignancies are on the rise. This includes some leukemia subtypes for men and women, as well as myeloma for men.
Leukemia is the leading cause of cancer death for men ages 20 to 39, but leukemia is no longer the leading cause of cancer death among children and adolescents (of both genders).
These and other data are included in the report, which is published in CA: A Cancer Journal for Clinicians.
The report estimates there will be 1,685,210 new cancer cases and 595,690 cancer deaths in the US in 2016. This includes 81,080 new lymphoma cases and 21,270 lymphoma deaths, 60,140 new leukemia cases and 24,400 leukemia deaths, and 30,330 new myeloma cases and 12,650 myeloma deaths.
Cancer incidence over time
The report suggests the overall cancer incidence for women has been stable from 1998 to 2012. But the incidence for men has declined by 3.1% per year from 2009 to 2012, with one-half of the drop in men due to recent rapid declines in prostate cancer diagnoses as prostate-specific antigen testing decreases.
Incidence rates increased from 2003 to 2012 among both men and women for some leukemia subtypes and for cancers of the tongue, tonsil, small intestine, liver, pancreas, kidney, renal pelvis, and thyroid.
Incidence rates increased in men for melanoma, myeloma, and cancers of the breast, testis, and oropharynx. Among women, incidence rates increased for cancers of the anus, vulva, and uterine corpus.
Cancer deaths
The rate of cancer deaths in the US has dropped 23% from its peak in 1991 to 2012. The incidence of cancer death was 215.1 per 100,000 in 1991 and 166.4 per 100,000 in 2012.
The decline is larger in men (28% since 1990) than in women (19% since 1991). Over the past decade of data, the rate dropped by 1.8% per year in men and 1.4% per year in women.
The decline in cancer death rates over the past 2 decades is driven by continued decreases in death rates for the 4 major cancer sites: lung, breast, prostate, and colon/rectum.
Breast cancer is the leading cause of cancer death in women ages 20 to 59, while lung cancer is the leading cause of cancer death in women 60 and older.
Among men, leukemia is the leading cause of cancer death for those ages 20 to 39, whereas lung cancer ranks first among men 40 and older.
Among children and adolescents (0-19), brain cancer has surpassed leukemia as the leading cause of cancer death, a result of more rapid therapeutic advances against leukemia.
The report also features an analysis of leading causes of death by state. It shows that, even as cancer remains the second leading cause of death nationwide, steep drops in deaths from heart disease have made cancer the leading cause of death in 21 states: Alaska, Arizona, Colorado, Delaware, Florida, Georgia, Idaho, Kansas, Maine, Massachusetts, Minnesota, Montana, Nebraska, New Hampshire, New Mexico, North Carolina, Oregon, South Carolina, Vermont, Virginia, and Washington.
In addition, cancer is the leading cause of death among adults ages 40 to 79 and among both Hispanics and Asian/Pacific Islanders, who together make up one-quarter of the US population.
Heart disease remains the top cause of death overall in the US. In 2012, there were 599,711 (24%) deaths from heart disease, compared to 582,623 (23%) deaths from cancer.
“We’re gratified to see cancer death rates continuing to drop,” said Otis W. Brawley, MD, chief medical officer of the American Cancer Society.
“But the fact that cancer is nonetheless becoming the top cause of death in many populations is a strong reminder that the fight is not over.”
patient and her father
Photo by Rhoda Baer
The American Cancer Society’s 2016 report on cancer in the US suggests that, in recent years, overall trends in cancer incidence have remained stable for women and declined for men.
However, the rates of certain malignancies are on the rise. This includes some leukemia subtypes for men and women, as well as myeloma for men.
Leukemia is the leading cause of cancer death for men ages 20 to 39, but leukemia is no longer the leading cause of cancer death among children and adolescents (of both genders).
These and other data are included in the report, which is published in CA: A Cancer Journal for Clinicians.
The report estimates there will be 1,685,210 new cancer cases and 595,690 cancer deaths in the US in 2016. This includes 81,080 new lymphoma cases and 21,270 lymphoma deaths, 60,140 new leukemia cases and 24,400 leukemia deaths, and 30,330 new myeloma cases and 12,650 myeloma deaths.
Cancer incidence over time
The report suggests the overall cancer incidence for women has been stable from 1998 to 2012. But the incidence for men has declined by 3.1% per year from 2009 to 2012, with one-half of the drop in men due to recent rapid declines in prostate cancer diagnoses as prostate-specific antigen testing decreases.
Incidence rates increased from 2003 to 2012 among both men and women for some leukemia subtypes and for cancers of the tongue, tonsil, small intestine, liver, pancreas, kidney, renal pelvis, and thyroid.
Incidence rates increased in men for melanoma, myeloma, and cancers of the breast, testis, and oropharynx. Among women, incidence rates increased for cancers of the anus, vulva, and uterine corpus.
Cancer deaths
The rate of cancer deaths in the US has dropped 23% from its peak in 1991 to 2012. The incidence of cancer death was 215.1 per 100,000 in 1991 and 166.4 per 100,000 in 2012.
The decline is larger in men (28% since 1990) than in women (19% since 1991). Over the past decade of data, the rate dropped by 1.8% per year in men and 1.4% per year in women.
The decline in cancer death rates over the past 2 decades is driven by continued decreases in death rates for the 4 major cancer sites: lung, breast, prostate, and colon/rectum.
Breast cancer is the leading cause of cancer death in women ages 20 to 59, while lung cancer is the leading cause of cancer death in women 60 and older.
Among men, leukemia is the leading cause of cancer death for those ages 20 to 39, whereas lung cancer ranks first among men 40 and older.
Among children and adolescents (0-19), brain cancer has surpassed leukemia as the leading cause of cancer death, a result of more rapid therapeutic advances against leukemia.
The report also features an analysis of leading causes of death by state. It shows that, even as cancer remains the second leading cause of death nationwide, steep drops in deaths from heart disease have made cancer the leading cause of death in 21 states: Alaska, Arizona, Colorado, Delaware, Florida, Georgia, Idaho, Kansas, Maine, Massachusetts, Minnesota, Montana, Nebraska, New Hampshire, New Mexico, North Carolina, Oregon, South Carolina, Vermont, Virginia, and Washington.
In addition, cancer is the leading cause of death among adults ages 40 to 79 and among both Hispanics and Asian/Pacific Islanders, who together make up one-quarter of the US population.
Heart disease remains the top cause of death overall in the US. In 2012, there were 599,711 (24%) deaths from heart disease, compared to 582,623 (23%) deaths from cancer.
“We’re gratified to see cancer death rates continuing to drop,” said Otis W. Brawley, MD, chief medical officer of the American Cancer Society.
“But the fact that cancer is nonetheless becoming the top cause of death in many populations is a strong reminder that the fight is not over.”
patient and her father
Photo by Rhoda Baer
The American Cancer Society’s 2016 report on cancer in the US suggests that, in recent years, overall trends in cancer incidence have remained stable for women and declined for men.
However, the rates of certain malignancies are on the rise. This includes some leukemia subtypes for men and women, as well as myeloma for men.
Leukemia is the leading cause of cancer death for men ages 20 to 39, but leukemia is no longer the leading cause of cancer death among children and adolescents (of both genders).
These and other data are included in the report, which is published in CA: A Cancer Journal for Clinicians.
The report estimates there will be 1,685,210 new cancer cases and 595,690 cancer deaths in the US in 2016. This includes 81,080 new lymphoma cases and 21,270 lymphoma deaths, 60,140 new leukemia cases and 24,400 leukemia deaths, and 30,330 new myeloma cases and 12,650 myeloma deaths.
Cancer incidence over time
The report suggests the overall cancer incidence for women has been stable from 1998 to 2012. But the incidence for men has declined by 3.1% per year from 2009 to 2012, with one-half of the drop in men due to recent rapid declines in prostate cancer diagnoses as prostate-specific antigen testing decreases.
Incidence rates increased from 2003 to 2012 among both men and women for some leukemia subtypes and for cancers of the tongue, tonsil, small intestine, liver, pancreas, kidney, renal pelvis, and thyroid.
Incidence rates increased in men for melanoma, myeloma, and cancers of the breast, testis, and oropharynx. Among women, incidence rates increased for cancers of the anus, vulva, and uterine corpus.
Cancer deaths
The rate of cancer deaths in the US has dropped 23% from its peak in 1991 to 2012. The incidence of cancer death was 215.1 per 100,000 in 1991 and 166.4 per 100,000 in 2012.
The decline is larger in men (28% since 1990) than in women (19% since 1991). Over the past decade of data, the rate dropped by 1.8% per year in men and 1.4% per year in women.
The decline in cancer death rates over the past 2 decades is driven by continued decreases in death rates for the 4 major cancer sites: lung, breast, prostate, and colon/rectum.
Breast cancer is the leading cause of cancer death in women ages 20 to 59, while lung cancer is the leading cause of cancer death in women 60 and older.
Among men, leukemia is the leading cause of cancer death for those ages 20 to 39, whereas lung cancer ranks first among men 40 and older.
Among children and adolescents (0-19), brain cancer has surpassed leukemia as the leading cause of cancer death, a result of more rapid therapeutic advances against leukemia.
The report also features an analysis of leading causes of death by state. It shows that, even as cancer remains the second leading cause of death nationwide, steep drops in deaths from heart disease have made cancer the leading cause of death in 21 states: Alaska, Arizona, Colorado, Delaware, Florida, Georgia, Idaho, Kansas, Maine, Massachusetts, Minnesota, Montana, Nebraska, New Hampshire, New Mexico, North Carolina, Oregon, South Carolina, Vermont, Virginia, and Washington.
In addition, cancer is the leading cause of death among adults ages 40 to 79 and among both Hispanics and Asian/Pacific Islanders, who together make up one-quarter of the US population.
Heart disease remains the top cause of death overall in the US. In 2012, there were 599,711 (24%) deaths from heart disease, compared to 582,623 (23%) deaths from cancer.
“We’re gratified to see cancer death rates continuing to drop,” said Otis W. Brawley, MD, chief medical officer of the American Cancer Society.
“But the fact that cancer is nonetheless becoming the top cause of death in many populations is a strong reminder that the fight is not over.”
Drug produces ‘encouraging efficacy’ in MM
© ASCO/Todd Buchanan
Single-agent daratumumab has exhibited “encouraging efficacy” and a “favorable safety profile” in patients with heavily pretreated and refractory multiple myeloma (MM), according to investigators from the phase 2 SIRIUS trial.
The drug produced an overall response rate of 30% in MM patients who had received 3 or more prior lines of therapy. The median progression-free survival was close to 4 months, and the median overall survival was nearly 18 months.
Thirty percent of patients had treatment-emergent serious adverse events (AEs), and 23% had grade 3 or 4 treatment-emergent serious AEs.
“This represents the first single-agent activity we have for a monoclonal antibody in treating multiple myeloma,” said study author Sagar Lonial, MD, of Emory University School of Medicine in Atlanta, Georgia.
“The future hope for daratumumab is in our ability to bring this active agent to earlier lines of therapy and combine it with drugs where you may get synergy.”
Dr Lonial and his colleagues reported results from the ongoing SIRIUS trial in The Lancet. Results from the trial were previously presented at the 2015 ASCO Annual Meeting. The research was funded by Janssen Research & Development, the company developing daratumumab.
In part 1 of the trial, 34 MM patients were randomized to receive either 8 mg/kg of daratumumab once every 4 weeks or 16 mg/kg once a week for 8 weeks, then once every 2 weeks for 16 weeks and once every 4 weeks after that, until disease progression or unacceptable toxicity.
In part 2, an additional 90 MM patients were enrolled and received 16 mg/kg of daratumumab on the same dosing schedule as in part 1.
Dr Lonial and his colleagues reported results for all patients who received 16 mg/kg of daratumumab. At the first interim analysis, the 8 mg/kg arm did not meet the criteria for expansion because the overall response rate was 11.1%.
The 106 patients who received the 16 mg/kg dose of daratumumab had received a median of 5 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug. Ninety-seven percent of these patients were refractory to their last line of therapy, and 95% were refractory to both a proteasome inhibitor and an immunomodulatory drug.
Response and survival
According to an independent review committee, 29.2% of patients responded to daratumumab. Eighteen patients had a partial response, 10 had a very good partial response, and 3 had a stringent complete response.
The median duration of response was 7.4 months, and the median time to first response was 1 month.
The median overall survival was 17.5 months, and the 12-month overall survival was 64.8%. The median progression-free survival was 3.7 months.
Safety
The most common AEs were fatigue (40%), anemia (33%), nausea (29%), thrombocytopenia (25%), neutropenia (23%), back pain (22%), and cough (21%). Thirty percent of patients experienced serious AEs, and 23% had serious grade 3/4 AEs.
Infusion-related reactions were reported in 42% of patients and were predominantly grade 1 or 2 (5% grade 3; no grade 4). The most common infusion-related reactions were nasal congestion (12%), throat irritation (7%), cough (6%), dyspnea (6%), chills (6%), and vomiting (6%)—all of which were treated with standard of care and slower infusion rates.
None of the patients discontinued daratumumab because of drug-related treatment-emergent AEs, infusion-related reactions, or death. However, 5% of patients discontinued treatment because of treatment-emergent AEs—2 cases of progressive disease and 1 case each of H1N1 influenza, hypercalcemia, and spinal cord compression.
Twenty-nine percent of patients died after treatment—27% due to progressive disease and 2% due to AEs. The 2 AEs were cardiorespiratory failure secondary to H1N1 influenza complications and general health deterioration secondary to complications of aspiration pneumonia.
© ASCO/Todd Buchanan
Single-agent daratumumab has exhibited “encouraging efficacy” and a “favorable safety profile” in patients with heavily pretreated and refractory multiple myeloma (MM), according to investigators from the phase 2 SIRIUS trial.
The drug produced an overall response rate of 30% in MM patients who had received 3 or more prior lines of therapy. The median progression-free survival was close to 4 months, and the median overall survival was nearly 18 months.
Thirty percent of patients had treatment-emergent serious adverse events (AEs), and 23% had grade 3 or 4 treatment-emergent serious AEs.
“This represents the first single-agent activity we have for a monoclonal antibody in treating multiple myeloma,” said study author Sagar Lonial, MD, of Emory University School of Medicine in Atlanta, Georgia.
“The future hope for daratumumab is in our ability to bring this active agent to earlier lines of therapy and combine it with drugs where you may get synergy.”
Dr Lonial and his colleagues reported results from the ongoing SIRIUS trial in The Lancet. Results from the trial were previously presented at the 2015 ASCO Annual Meeting. The research was funded by Janssen Research & Development, the company developing daratumumab.
In part 1 of the trial, 34 MM patients were randomized to receive either 8 mg/kg of daratumumab once every 4 weeks or 16 mg/kg once a week for 8 weeks, then once every 2 weeks for 16 weeks and once every 4 weeks after that, until disease progression or unacceptable toxicity.
In part 2, an additional 90 MM patients were enrolled and received 16 mg/kg of daratumumab on the same dosing schedule as in part 1.
Dr Lonial and his colleagues reported results for all patients who received 16 mg/kg of daratumumab. At the first interim analysis, the 8 mg/kg arm did not meet the criteria for expansion because the overall response rate was 11.1%.
The 106 patients who received the 16 mg/kg dose of daratumumab had received a median of 5 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug. Ninety-seven percent of these patients were refractory to their last line of therapy, and 95% were refractory to both a proteasome inhibitor and an immunomodulatory drug.
Response and survival
According to an independent review committee, 29.2% of patients responded to daratumumab. Eighteen patients had a partial response, 10 had a very good partial response, and 3 had a stringent complete response.
The median duration of response was 7.4 months, and the median time to first response was 1 month.
The median overall survival was 17.5 months, and the 12-month overall survival was 64.8%. The median progression-free survival was 3.7 months.
Safety
The most common AEs were fatigue (40%), anemia (33%), nausea (29%), thrombocytopenia (25%), neutropenia (23%), back pain (22%), and cough (21%). Thirty percent of patients experienced serious AEs, and 23% had serious grade 3/4 AEs.
Infusion-related reactions were reported in 42% of patients and were predominantly grade 1 or 2 (5% grade 3; no grade 4). The most common infusion-related reactions were nasal congestion (12%), throat irritation (7%), cough (6%), dyspnea (6%), chills (6%), and vomiting (6%)—all of which were treated with standard of care and slower infusion rates.
None of the patients discontinued daratumumab because of drug-related treatment-emergent AEs, infusion-related reactions, or death. However, 5% of patients discontinued treatment because of treatment-emergent AEs—2 cases of progressive disease and 1 case each of H1N1 influenza, hypercalcemia, and spinal cord compression.
Twenty-nine percent of patients died after treatment—27% due to progressive disease and 2% due to AEs. The 2 AEs were cardiorespiratory failure secondary to H1N1 influenza complications and general health deterioration secondary to complications of aspiration pneumonia.
© ASCO/Todd Buchanan
Single-agent daratumumab has exhibited “encouraging efficacy” and a “favorable safety profile” in patients with heavily pretreated and refractory multiple myeloma (MM), according to investigators from the phase 2 SIRIUS trial.
The drug produced an overall response rate of 30% in MM patients who had received 3 or more prior lines of therapy. The median progression-free survival was close to 4 months, and the median overall survival was nearly 18 months.
Thirty percent of patients had treatment-emergent serious adverse events (AEs), and 23% had grade 3 or 4 treatment-emergent serious AEs.
“This represents the first single-agent activity we have for a monoclonal antibody in treating multiple myeloma,” said study author Sagar Lonial, MD, of Emory University School of Medicine in Atlanta, Georgia.
“The future hope for daratumumab is in our ability to bring this active agent to earlier lines of therapy and combine it with drugs where you may get synergy.”
Dr Lonial and his colleagues reported results from the ongoing SIRIUS trial in The Lancet. Results from the trial were previously presented at the 2015 ASCO Annual Meeting. The research was funded by Janssen Research & Development, the company developing daratumumab.
In part 1 of the trial, 34 MM patients were randomized to receive either 8 mg/kg of daratumumab once every 4 weeks or 16 mg/kg once a week for 8 weeks, then once every 2 weeks for 16 weeks and once every 4 weeks after that, until disease progression or unacceptable toxicity.
In part 2, an additional 90 MM patients were enrolled and received 16 mg/kg of daratumumab on the same dosing schedule as in part 1.
Dr Lonial and his colleagues reported results for all patients who received 16 mg/kg of daratumumab. At the first interim analysis, the 8 mg/kg arm did not meet the criteria for expansion because the overall response rate was 11.1%.
The 106 patients who received the 16 mg/kg dose of daratumumab had received a median of 5 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug. Ninety-seven percent of these patients were refractory to their last line of therapy, and 95% were refractory to both a proteasome inhibitor and an immunomodulatory drug.
Response and survival
According to an independent review committee, 29.2% of patients responded to daratumumab. Eighteen patients had a partial response, 10 had a very good partial response, and 3 had a stringent complete response.
The median duration of response was 7.4 months, and the median time to first response was 1 month.
The median overall survival was 17.5 months, and the 12-month overall survival was 64.8%. The median progression-free survival was 3.7 months.
Safety
The most common AEs were fatigue (40%), anemia (33%), nausea (29%), thrombocytopenia (25%), neutropenia (23%), back pain (22%), and cough (21%). Thirty percent of patients experienced serious AEs, and 23% had serious grade 3/4 AEs.
Infusion-related reactions were reported in 42% of patients and were predominantly grade 1 or 2 (5% grade 3; no grade 4). The most common infusion-related reactions were nasal congestion (12%), throat irritation (7%), cough (6%), dyspnea (6%), chills (6%), and vomiting (6%)—all of which were treated with standard of care and slower infusion rates.
None of the patients discontinued daratumumab because of drug-related treatment-emergent AEs, infusion-related reactions, or death. However, 5% of patients discontinued treatment because of treatment-emergent AEs—2 cases of progressive disease and 1 case each of H1N1 influenza, hypercalcemia, and spinal cord compression.
Twenty-nine percent of patients died after treatment—27% due to progressive disease and 2% due to AEs. The 2 AEs were cardiorespiratory failure secondary to H1N1 influenza complications and general health deterioration secondary to complications of aspiration pneumonia.
Paste may reduce radiation-induced fibrosis
woman for radiation
Photo by Rhoda Baer
A topical paste can reduce fibrosis caused by radiation therapy, according to preclinical research published in The FASEB Journal.
The study addressed a type of fibrosis called radiation dermatitis, in which radiation applied to the skin causes the buildup of fibrotic tissue and skin thickening.
To test their topical paste, researchers mimicked the development of radiation dermatitis in mice.
They exposed the mice’s skin to a single dose of 40 Gy, an amount of radiation similar to what patients undergoing anticancer radiation typically receive over 5 weeks.
Some of the irradiated animals were wild-type mice, while others were genetically engineered to lack the A2A receptor (A2AR). The researchers had previously shown that occupancy of A2AR induces collagen production.
The wild-type mice went on to receive placebo or daily treatment with ZM241385, a paste made with the research team’s patented A2AR blocker. The paste contains 2.5 milligrams of active ingredient per milliliter of 3% carboxymethyl cellulose, a gum “binder.”
A month after exposure, wild-type mice that received placebo had a nearly 2-fold increase in the amount of collagen and skin thickness. These mice also experienced epithelial hyperplasia.
On the other hand, mice treated with ZM241385 accumulated only 10% more skin-thickening collagen. ZM241385 treatment reduced the number of myofibroblasts, collagen fibrils, proliferating keratinocytes, and angiogenesis when compared to placebo. And the paste prevented epithelial hyperplasia.
Like ZM241385-treated mice, A2AR knockout mice did not have the excessive collagen production and skin thickening observed in placebo-treated wild-type mice. The knockout mice also exhibited reductions in myofibroblast content, angiogenesis, and epithelial hyperplasia.
The researchers noted that radiation-induced changes in the dermis and epidermis were accompanied by an infiltrate of T cells, which was prevented in both ZM241385-treated and A2AR knockout mice.
“Our latest study is the first to demonstrate that blocking or deleting the A2A receptor can be useful in reducing radiation-induced scarring in skin,” said study author Bruce Cronstein, MD, of New York University School of Medicine in New York, New York.
“The study also suggests that adenosine A2A receptor antagonists may have broad applications as drug therapies for preventing fibrosis and scarring, not just in the liver but also in the skin.”
If further experiments prove successful, Dr Cronstein said, clinicians treating early stage cancers with radiation could eventually prescribe an A2AR inhibitor paste to prevent fibrosis. He said his team next plans to study the mechanism underlying A2AR’s role in fibrosis.
woman for radiation
Photo by Rhoda Baer
A topical paste can reduce fibrosis caused by radiation therapy, according to preclinical research published in The FASEB Journal.
The study addressed a type of fibrosis called radiation dermatitis, in which radiation applied to the skin causes the buildup of fibrotic tissue and skin thickening.
To test their topical paste, researchers mimicked the development of radiation dermatitis in mice.
They exposed the mice’s skin to a single dose of 40 Gy, an amount of radiation similar to what patients undergoing anticancer radiation typically receive over 5 weeks.
Some of the irradiated animals were wild-type mice, while others were genetically engineered to lack the A2A receptor (A2AR). The researchers had previously shown that occupancy of A2AR induces collagen production.
The wild-type mice went on to receive placebo or daily treatment with ZM241385, a paste made with the research team’s patented A2AR blocker. The paste contains 2.5 milligrams of active ingredient per milliliter of 3% carboxymethyl cellulose, a gum “binder.”
A month after exposure, wild-type mice that received placebo had a nearly 2-fold increase in the amount of collagen and skin thickness. These mice also experienced epithelial hyperplasia.
On the other hand, mice treated with ZM241385 accumulated only 10% more skin-thickening collagen. ZM241385 treatment reduced the number of myofibroblasts, collagen fibrils, proliferating keratinocytes, and angiogenesis when compared to placebo. And the paste prevented epithelial hyperplasia.
Like ZM241385-treated mice, A2AR knockout mice did not have the excessive collagen production and skin thickening observed in placebo-treated wild-type mice. The knockout mice also exhibited reductions in myofibroblast content, angiogenesis, and epithelial hyperplasia.
The researchers noted that radiation-induced changes in the dermis and epidermis were accompanied by an infiltrate of T cells, which was prevented in both ZM241385-treated and A2AR knockout mice.
“Our latest study is the first to demonstrate that blocking or deleting the A2A receptor can be useful in reducing radiation-induced scarring in skin,” said study author Bruce Cronstein, MD, of New York University School of Medicine in New York, New York.
“The study also suggests that adenosine A2A receptor antagonists may have broad applications as drug therapies for preventing fibrosis and scarring, not just in the liver but also in the skin.”
If further experiments prove successful, Dr Cronstein said, clinicians treating early stage cancers with radiation could eventually prescribe an A2AR inhibitor paste to prevent fibrosis. He said his team next plans to study the mechanism underlying A2AR’s role in fibrosis.
woman for radiation
Photo by Rhoda Baer
A topical paste can reduce fibrosis caused by radiation therapy, according to preclinical research published in The FASEB Journal.
The study addressed a type of fibrosis called radiation dermatitis, in which radiation applied to the skin causes the buildup of fibrotic tissue and skin thickening.
To test their topical paste, researchers mimicked the development of radiation dermatitis in mice.
They exposed the mice’s skin to a single dose of 40 Gy, an amount of radiation similar to what patients undergoing anticancer radiation typically receive over 5 weeks.
Some of the irradiated animals were wild-type mice, while others were genetically engineered to lack the A2A receptor (A2AR). The researchers had previously shown that occupancy of A2AR induces collagen production.
The wild-type mice went on to receive placebo or daily treatment with ZM241385, a paste made with the research team’s patented A2AR blocker. The paste contains 2.5 milligrams of active ingredient per milliliter of 3% carboxymethyl cellulose, a gum “binder.”
A month after exposure, wild-type mice that received placebo had a nearly 2-fold increase in the amount of collagen and skin thickness. These mice also experienced epithelial hyperplasia.
On the other hand, mice treated with ZM241385 accumulated only 10% more skin-thickening collagen. ZM241385 treatment reduced the number of myofibroblasts, collagen fibrils, proliferating keratinocytes, and angiogenesis when compared to placebo. And the paste prevented epithelial hyperplasia.
Like ZM241385-treated mice, A2AR knockout mice did not have the excessive collagen production and skin thickening observed in placebo-treated wild-type mice. The knockout mice also exhibited reductions in myofibroblast content, angiogenesis, and epithelial hyperplasia.
The researchers noted that radiation-induced changes in the dermis and epidermis were accompanied by an infiltrate of T cells, which was prevented in both ZM241385-treated and A2AR knockout mice.
“Our latest study is the first to demonstrate that blocking or deleting the A2A receptor can be useful in reducing radiation-induced scarring in skin,” said study author Bruce Cronstein, MD, of New York University School of Medicine in New York, New York.
“The study also suggests that adenosine A2A receptor antagonists may have broad applications as drug therapies for preventing fibrosis and scarring, not just in the liver but also in the skin.”
If further experiments prove successful, Dr Cronstein said, clinicians treating early stage cancers with radiation could eventually prescribe an A2AR inhibitor paste to prevent fibrosis. He said his team next plans to study the mechanism underlying A2AR’s role in fibrosis.