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Exercise during chemotherapy may yield long-term physical benefits
ORLANDO – Physical exercise during adjuvant chemotherapy may lead to improved physical activity and decreased fatigue years after the treatment is completed, results of a recent analysis suggest.
Four years after participating in an exercise program that took place during cancer treatment, patients reported more moderate-to-vigorous activity and less fatigue, compared with patients who did not participate in the program, according to long-term follow-up results presented at the Cancer Survivorship Symposium.
“We think that offering exercise during cancer treatment, including chemotherapy, is recommended and has beneficial short- and long-term effects on health,” said Anne M. May, PhD, of University Medical Center, Utrecht, the Netherlands.
Speaking in a press conference at the symposium, Dr. May described results of the analysis, which included 128 patients who had previously participated in PACT, a 237-patient randomized controlled trial evaluating a supervised exercise program versus usual care in patients undergoing adjuvant treatment for breast or colon cancer.
The 18-week exercise program included moderate- to high-intensity aerobic and strength training under physical therapist supervision for 60 minutes twice weekly, plus home-based physical activity for 30 minutes three times weekly.
At 4 years’ follow-up, patients in the exercise group reported on average 90 minutes of moderate-to-vigorous exercise per week, compared to an average of 70 minutes per week in the usual care group (P less than .05), Dr. May reported at the symposium, which was sponsored by the American Academy of Family Physicians, the American College of Physicians, and the American Society of Clinical Oncology.
There was also a trend toward decreased fatigue reported in the exercise vs. usual care group, though the finding did not reach statistical significance, she said.
It is “encouraging” to see that this exercise program had a long-term impact on patients’ physical activity levels, said ASCO expert Timothy Gilligan, MD, MSc.
“I think the public sometimes gets jaded because the nutritional recommendations seem to change every year, but if you look at the research on exercise in health … it’s interesting how consistent the data is that exercise really is good for us – if we can only get people to do it,” said Dr. Gilligan, who moderated the press conference.
Dr. May said she had no disclosures to report for the study, which was supported by grants from the Dutch Cancer Society, the Dutch Pink Ribbon Foundation, and the Netherlands Organization for Health Research.
SOURCE: May AM et al. Cancer Survivorship Symposium, Abstract 99.
ORLANDO – Physical exercise during adjuvant chemotherapy may lead to improved physical activity and decreased fatigue years after the treatment is completed, results of a recent analysis suggest.
Four years after participating in an exercise program that took place during cancer treatment, patients reported more moderate-to-vigorous activity and less fatigue, compared with patients who did not participate in the program, according to long-term follow-up results presented at the Cancer Survivorship Symposium.
“We think that offering exercise during cancer treatment, including chemotherapy, is recommended and has beneficial short- and long-term effects on health,” said Anne M. May, PhD, of University Medical Center, Utrecht, the Netherlands.
Speaking in a press conference at the symposium, Dr. May described results of the analysis, which included 128 patients who had previously participated in PACT, a 237-patient randomized controlled trial evaluating a supervised exercise program versus usual care in patients undergoing adjuvant treatment for breast or colon cancer.
The 18-week exercise program included moderate- to high-intensity aerobic and strength training under physical therapist supervision for 60 minutes twice weekly, plus home-based physical activity for 30 minutes three times weekly.
At 4 years’ follow-up, patients in the exercise group reported on average 90 minutes of moderate-to-vigorous exercise per week, compared to an average of 70 minutes per week in the usual care group (P less than .05), Dr. May reported at the symposium, which was sponsored by the American Academy of Family Physicians, the American College of Physicians, and the American Society of Clinical Oncology.
There was also a trend toward decreased fatigue reported in the exercise vs. usual care group, though the finding did not reach statistical significance, she said.
It is “encouraging” to see that this exercise program had a long-term impact on patients’ physical activity levels, said ASCO expert Timothy Gilligan, MD, MSc.
“I think the public sometimes gets jaded because the nutritional recommendations seem to change every year, but if you look at the research on exercise in health … it’s interesting how consistent the data is that exercise really is good for us – if we can only get people to do it,” said Dr. Gilligan, who moderated the press conference.
Dr. May said she had no disclosures to report for the study, which was supported by grants from the Dutch Cancer Society, the Dutch Pink Ribbon Foundation, and the Netherlands Organization for Health Research.
SOURCE: May AM et al. Cancer Survivorship Symposium, Abstract 99.
ORLANDO – Physical exercise during adjuvant chemotherapy may lead to improved physical activity and decreased fatigue years after the treatment is completed, results of a recent analysis suggest.
Four years after participating in an exercise program that took place during cancer treatment, patients reported more moderate-to-vigorous activity and less fatigue, compared with patients who did not participate in the program, according to long-term follow-up results presented at the Cancer Survivorship Symposium.
“We think that offering exercise during cancer treatment, including chemotherapy, is recommended and has beneficial short- and long-term effects on health,” said Anne M. May, PhD, of University Medical Center, Utrecht, the Netherlands.
Speaking in a press conference at the symposium, Dr. May described results of the analysis, which included 128 patients who had previously participated in PACT, a 237-patient randomized controlled trial evaluating a supervised exercise program versus usual care in patients undergoing adjuvant treatment for breast or colon cancer.
The 18-week exercise program included moderate- to high-intensity aerobic and strength training under physical therapist supervision for 60 minutes twice weekly, plus home-based physical activity for 30 minutes three times weekly.
At 4 years’ follow-up, patients in the exercise group reported on average 90 minutes of moderate-to-vigorous exercise per week, compared to an average of 70 minutes per week in the usual care group (P less than .05), Dr. May reported at the symposium, which was sponsored by the American Academy of Family Physicians, the American College of Physicians, and the American Society of Clinical Oncology.
There was also a trend toward decreased fatigue reported in the exercise vs. usual care group, though the finding did not reach statistical significance, she said.
It is “encouraging” to see that this exercise program had a long-term impact on patients’ physical activity levels, said ASCO expert Timothy Gilligan, MD, MSc.
“I think the public sometimes gets jaded because the nutritional recommendations seem to change every year, but if you look at the research on exercise in health … it’s interesting how consistent the data is that exercise really is good for us – if we can only get people to do it,” said Dr. Gilligan, who moderated the press conference.
Dr. May said she had no disclosures to report for the study, which was supported by grants from the Dutch Cancer Society, the Dutch Pink Ribbon Foundation, and the Netherlands Organization for Health Research.
SOURCE: May AM et al. Cancer Survivorship Symposium, Abstract 99.
REPORTING FROM CSC 2018
Key clinical point: Exercise during adjuvant chemotherapy may lead to lower levels of fatigue and higher levels of physical activity years after treatment is completed.
Major finding: Four years after participating in an 18-week exercise program during cancer treatment, patients reported an average of 90 minutes of moderate-to-vigorous physical activity per day, compared with 70 minutes for patients who did not participate (P less than .05).
Study details: Long-term follow-up of 128 patients who had participated in the PACT study, a randomized controlled trial of a supervised exercise program versus usual care in breast and colon cancer patients undergoing adjuvant treatment including chemotherapy.
Disclosures: The authors reported no disclosures relevant to the study, which was supported by grants from the Dutch Cancer Society, the Dutch Pink Ribbon Foundation, and the Netherlands Organization for Health Research.
Source: May AM et al. Cancer Survivorship Symposium, Abstract 99.
Radiation exposure in MICU may exceed recommended limit
according to results of a recent observational study.
These “substantial” radiation doses in some patients suggest that efforts are warranted to “justify, restrict and optimize” the use of radiological resources when possible, said Sudhir Krishnan, MD, of the Cleveland Clinic, and his coauthors.
The retrospective, observational study included 4,155 adult admissions to a medical intensive care unit (MICU) at an academic medical center in 2013. Investigators calculated the cumulative effective dose (CED) of radiation based on reported ionizing radiological studies for each patient.
With a median length of stay of just 6.4 days, a total of 131 admissions (3%) accrued a CED of radiation of at least 50 millisieverts (mSv), the annual limit recommended by the National Commission on Radiation Protection, and 47 of those patients (1%) accrued a CED of radiation of at least 100 mSv, the 5-year cumulative exposure limit, the authors reported.
These findings suggest that “MICU patients could be subjected to radiation doses in a matter of days that are equivalent to or more than [the] CED observed in patients with chronic diseases and patients with trauma,” wrote Dr. Krishnan and his coauthors.
As hypothesized, patients with higher severity of illness scores (APACHE III scores) received a higher CED of radiation, according to the report. Using a multivariable linear regression model, investigators found that higher CED was predicted by higher APACHE III scores, sepsis, longer MICU stay, and gastrointestinal disorders and bleeding.
CT scans were the most common source of radiation exposure in patients who exceeded a 50 mSv of radiation, accounting for 49% of the total accrued dose, with interventional radiology accounting for 38%, authors reported.
Despite concerns about “the statistical risk of latent radiogenic cancer,” radiologic studies performed in the critically ill have the potential to reduce morbidity and mortality, the authors acknowledged in a discussion of the results.
“This understandably shifts the risk-benefit ratio towards radiation exposure,” the researchers wrote. “However, complacency in this regard cannot be entirely justified.”
Of the patients in the study who were exposed to a CED of at least 50 mSv, 81% survived the hospital admission and could be subjected to even more radiation as a part of ongoing medical care, they noted.
“Robust tools for monitoring CED prospectively per episode of clinical care, counseling patients exposed to high doses of radiation, and prospective studies exploring radiogenic risk associated with medical radiation are urgently required,” the authors said.
Dr. Krishnan and his coauthors reported no significant conflicts of interest.
SOURCE: Krishnan S et al. Chest. 2018 Feb 4. doi: 10.1016/j.chest.2018.01.019.
according to results of a recent observational study.
These “substantial” radiation doses in some patients suggest that efforts are warranted to “justify, restrict and optimize” the use of radiological resources when possible, said Sudhir Krishnan, MD, of the Cleveland Clinic, and his coauthors.
The retrospective, observational study included 4,155 adult admissions to a medical intensive care unit (MICU) at an academic medical center in 2013. Investigators calculated the cumulative effective dose (CED) of radiation based on reported ionizing radiological studies for each patient.
With a median length of stay of just 6.4 days, a total of 131 admissions (3%) accrued a CED of radiation of at least 50 millisieverts (mSv), the annual limit recommended by the National Commission on Radiation Protection, and 47 of those patients (1%) accrued a CED of radiation of at least 100 mSv, the 5-year cumulative exposure limit, the authors reported.
These findings suggest that “MICU patients could be subjected to radiation doses in a matter of days that are equivalent to or more than [the] CED observed in patients with chronic diseases and patients with trauma,” wrote Dr. Krishnan and his coauthors.
As hypothesized, patients with higher severity of illness scores (APACHE III scores) received a higher CED of radiation, according to the report. Using a multivariable linear regression model, investigators found that higher CED was predicted by higher APACHE III scores, sepsis, longer MICU stay, and gastrointestinal disorders and bleeding.
CT scans were the most common source of radiation exposure in patients who exceeded a 50 mSv of radiation, accounting for 49% of the total accrued dose, with interventional radiology accounting for 38%, authors reported.
Despite concerns about “the statistical risk of latent radiogenic cancer,” radiologic studies performed in the critically ill have the potential to reduce morbidity and mortality, the authors acknowledged in a discussion of the results.
“This understandably shifts the risk-benefit ratio towards radiation exposure,” the researchers wrote. “However, complacency in this regard cannot be entirely justified.”
Of the patients in the study who were exposed to a CED of at least 50 mSv, 81% survived the hospital admission and could be subjected to even more radiation as a part of ongoing medical care, they noted.
“Robust tools for monitoring CED prospectively per episode of clinical care, counseling patients exposed to high doses of radiation, and prospective studies exploring radiogenic risk associated with medical radiation are urgently required,” the authors said.
Dr. Krishnan and his coauthors reported no significant conflicts of interest.
SOURCE: Krishnan S et al. Chest. 2018 Feb 4. doi: 10.1016/j.chest.2018.01.019.
according to results of a recent observational study.
These “substantial” radiation doses in some patients suggest that efforts are warranted to “justify, restrict and optimize” the use of radiological resources when possible, said Sudhir Krishnan, MD, of the Cleveland Clinic, and his coauthors.
The retrospective, observational study included 4,155 adult admissions to a medical intensive care unit (MICU) at an academic medical center in 2013. Investigators calculated the cumulative effective dose (CED) of radiation based on reported ionizing radiological studies for each patient.
With a median length of stay of just 6.4 days, a total of 131 admissions (3%) accrued a CED of radiation of at least 50 millisieverts (mSv), the annual limit recommended by the National Commission on Radiation Protection, and 47 of those patients (1%) accrued a CED of radiation of at least 100 mSv, the 5-year cumulative exposure limit, the authors reported.
These findings suggest that “MICU patients could be subjected to radiation doses in a matter of days that are equivalent to or more than [the] CED observed in patients with chronic diseases and patients with trauma,” wrote Dr. Krishnan and his coauthors.
As hypothesized, patients with higher severity of illness scores (APACHE III scores) received a higher CED of radiation, according to the report. Using a multivariable linear regression model, investigators found that higher CED was predicted by higher APACHE III scores, sepsis, longer MICU stay, and gastrointestinal disorders and bleeding.
CT scans were the most common source of radiation exposure in patients who exceeded a 50 mSv of radiation, accounting for 49% of the total accrued dose, with interventional radiology accounting for 38%, authors reported.
Despite concerns about “the statistical risk of latent radiogenic cancer,” radiologic studies performed in the critically ill have the potential to reduce morbidity and mortality, the authors acknowledged in a discussion of the results.
“This understandably shifts the risk-benefit ratio towards radiation exposure,” the researchers wrote. “However, complacency in this regard cannot be entirely justified.”
Of the patients in the study who were exposed to a CED of at least 50 mSv, 81% survived the hospital admission and could be subjected to even more radiation as a part of ongoing medical care, they noted.
“Robust tools for monitoring CED prospectively per episode of clinical care, counseling patients exposed to high doses of radiation, and prospective studies exploring radiogenic risk associated with medical radiation are urgently required,” the authors said.
Dr. Krishnan and his coauthors reported no significant conflicts of interest.
SOURCE: Krishnan S et al. Chest. 2018 Feb 4. doi: 10.1016/j.chest.2018.01.019.
FROM CHEST
Key clinical point: Patients admitted to MICUs may be exposed to doses of radiation that are substantial and may exceed federal occupational health limits.
Major finding: In a short span of time (median 6.4 days length of stay), 3% of MICU patients received a cumulative dose of radiation that exceeded the U.S. recommended limit, and 1% accrued enough exposure to exceed the 5-year cumulative limit.
Data source: A retrospective, observational study including 4,155 adult admissions to the MICU at an academic medical center in 2013.
Disclosures: The study authors reported no significant conflicts of interest.
Source: Krishnan S et al. Chest. 2018 Feb 4. doi: 10.1016/j.chest.2018.01.019.
Next-day discharge after TAVR shows promise
Compared with a longer hospital stay, next-day discharge (NDD) after minimalist transcatheter aortic valve replacement (TAVR) appears safe, according to a recently reported analysis of patients treated at a single center.
The composite endpoint of mortality and readmission at 30 days was similar for NDD, compared with later discharges among patients who had a procedure that met minimalist criteria, defined in this study as transfemoral TAVR under conscious sedation and local anesthesia.
Mortality and readmission at 1 year was lower in the NDD group, mainly because of a lower risk of noncardiovascular readmissions, study authors reported in JACC: Cardiovascular Interventions. “Although superior NDD outcomes are likely attributed to selected patient characteristics, NDD in patients without in-hospital complications may be appropriate after transfemoral balloon-expandable TAVR,” wrote Norihiko Kamioka, MD, division of cardiology, Emory University, Atlanta, and associates.
The retrospective, observational analysis included 663 consecutive patients who underwent elective balloon-expandable TAVR during July 2014–July 2016. Cases with complications after the procedure were excluded.
The final analysis, which included 150 patients who had NDD and 210 discharged later, showed no difference between groups in the composite endpoint of mortality, and that 30-day readmissions were similar between groups (hazard ratio, 0.62; 95% confidence interval, 0.20-1.91).
Mortality and readmission at 1 year, the primary endpoint chosen for the study, favored the NDD group (HR, 0.47; 95% CI, 0.27-0.81), but “this finding probably reflects a healthier cohort in the NDD group,” the investigators noted. Furthermore, “although the reason for the discrepancy in the composite outcome at 1 year is mainly driven by noncardiovascular readmission, other confounding variables cannot be entirely ruled out,” Dr. Kamioka and colleagues said in the report.
Predictors of NDD included male sex, no atrial fibrillation, lower serum creatinine level, and younger age, researchers also found.
A validation cohort would be needed to confirm the findings of this study, including predictors of favorable outcomes, and to apply NDD to a wider population, study authors said.
Dr. Kamioka reported no relationships relevant to the study. Study coauthors reported disclosures related to Edwards Lifesciences, Abbott Vascular, Medtronic, Gore Vascular, and Boston Scientific.
SOURCE: JACC: Cardiovascular Interventions. 2018 Jan 22. doi: 10.1016/j.jcin.2017.10.021.
Researchers at Emory University have been leaders in promoting the so-called minimalist approach to TAVR and helping others understand how to safely reduce the length of stay without reducing the quality of care in these patients; however, the present study has significant shortcomings” that “may raise more questions than answers.
Because of these exclusions, it is difficult to know from this study if this treatment is generalizable to a larger TAVR population.
The conclusion that there was no difference in the composite outcome of death and readmission at 30 days is helpful information, offering reassurance that patient safety is not being compromised with NDD; however, the finding of superior outcomes at 1 year in the NDD group was driven by a significant reduction in noncardiovascular readmissions, which merely reemphasizes that the NDD patients in this study were lower risk rather than that they benefited by NDD.
Molly Szerlip, MD, of the Heart Hospital Baylor Plano (Tex.) made these comments in an accompanying editorial (JACC: Cardiovasc Interven. 2018 Jan 22. doi: 10.1016/j.jcin.2017.12.001). She reported disclosures related to Edwards Lifesciences and Medtronic.
Researchers at Emory University have been leaders in promoting the so-called minimalist approach to TAVR and helping others understand how to safely reduce the length of stay without reducing the quality of care in these patients; however, the present study has significant shortcomings” that “may raise more questions than answers.
Because of these exclusions, it is difficult to know from this study if this treatment is generalizable to a larger TAVR population.
The conclusion that there was no difference in the composite outcome of death and readmission at 30 days is helpful information, offering reassurance that patient safety is not being compromised with NDD; however, the finding of superior outcomes at 1 year in the NDD group was driven by a significant reduction in noncardiovascular readmissions, which merely reemphasizes that the NDD patients in this study were lower risk rather than that they benefited by NDD.
Molly Szerlip, MD, of the Heart Hospital Baylor Plano (Tex.) made these comments in an accompanying editorial (JACC: Cardiovasc Interven. 2018 Jan 22. doi: 10.1016/j.jcin.2017.12.001). She reported disclosures related to Edwards Lifesciences and Medtronic.
Researchers at Emory University have been leaders in promoting the so-called minimalist approach to TAVR and helping others understand how to safely reduce the length of stay without reducing the quality of care in these patients; however, the present study has significant shortcomings” that “may raise more questions than answers.
Because of these exclusions, it is difficult to know from this study if this treatment is generalizable to a larger TAVR population.
The conclusion that there was no difference in the composite outcome of death and readmission at 30 days is helpful information, offering reassurance that patient safety is not being compromised with NDD; however, the finding of superior outcomes at 1 year in the NDD group was driven by a significant reduction in noncardiovascular readmissions, which merely reemphasizes that the NDD patients in this study were lower risk rather than that they benefited by NDD.
Molly Szerlip, MD, of the Heart Hospital Baylor Plano (Tex.) made these comments in an accompanying editorial (JACC: Cardiovasc Interven. 2018 Jan 22. doi: 10.1016/j.jcin.2017.12.001). She reported disclosures related to Edwards Lifesciences and Medtronic.
Compared with a longer hospital stay, next-day discharge (NDD) after minimalist transcatheter aortic valve replacement (TAVR) appears safe, according to a recently reported analysis of patients treated at a single center.
The composite endpoint of mortality and readmission at 30 days was similar for NDD, compared with later discharges among patients who had a procedure that met minimalist criteria, defined in this study as transfemoral TAVR under conscious sedation and local anesthesia.
Mortality and readmission at 1 year was lower in the NDD group, mainly because of a lower risk of noncardiovascular readmissions, study authors reported in JACC: Cardiovascular Interventions. “Although superior NDD outcomes are likely attributed to selected patient characteristics, NDD in patients without in-hospital complications may be appropriate after transfemoral balloon-expandable TAVR,” wrote Norihiko Kamioka, MD, division of cardiology, Emory University, Atlanta, and associates.
The retrospective, observational analysis included 663 consecutive patients who underwent elective balloon-expandable TAVR during July 2014–July 2016. Cases with complications after the procedure were excluded.
The final analysis, which included 150 patients who had NDD and 210 discharged later, showed no difference between groups in the composite endpoint of mortality, and that 30-day readmissions were similar between groups (hazard ratio, 0.62; 95% confidence interval, 0.20-1.91).
Mortality and readmission at 1 year, the primary endpoint chosen for the study, favored the NDD group (HR, 0.47; 95% CI, 0.27-0.81), but “this finding probably reflects a healthier cohort in the NDD group,” the investigators noted. Furthermore, “although the reason for the discrepancy in the composite outcome at 1 year is mainly driven by noncardiovascular readmission, other confounding variables cannot be entirely ruled out,” Dr. Kamioka and colleagues said in the report.
Predictors of NDD included male sex, no atrial fibrillation, lower serum creatinine level, and younger age, researchers also found.
A validation cohort would be needed to confirm the findings of this study, including predictors of favorable outcomes, and to apply NDD to a wider population, study authors said.
Dr. Kamioka reported no relationships relevant to the study. Study coauthors reported disclosures related to Edwards Lifesciences, Abbott Vascular, Medtronic, Gore Vascular, and Boston Scientific.
SOURCE: JACC: Cardiovascular Interventions. 2018 Jan 22. doi: 10.1016/j.jcin.2017.10.021.
Compared with a longer hospital stay, next-day discharge (NDD) after minimalist transcatheter aortic valve replacement (TAVR) appears safe, according to a recently reported analysis of patients treated at a single center.
The composite endpoint of mortality and readmission at 30 days was similar for NDD, compared with later discharges among patients who had a procedure that met minimalist criteria, defined in this study as transfemoral TAVR under conscious sedation and local anesthesia.
Mortality and readmission at 1 year was lower in the NDD group, mainly because of a lower risk of noncardiovascular readmissions, study authors reported in JACC: Cardiovascular Interventions. “Although superior NDD outcomes are likely attributed to selected patient characteristics, NDD in patients without in-hospital complications may be appropriate after transfemoral balloon-expandable TAVR,” wrote Norihiko Kamioka, MD, division of cardiology, Emory University, Atlanta, and associates.
The retrospective, observational analysis included 663 consecutive patients who underwent elective balloon-expandable TAVR during July 2014–July 2016. Cases with complications after the procedure were excluded.
The final analysis, which included 150 patients who had NDD and 210 discharged later, showed no difference between groups in the composite endpoint of mortality, and that 30-day readmissions were similar between groups (hazard ratio, 0.62; 95% confidence interval, 0.20-1.91).
Mortality and readmission at 1 year, the primary endpoint chosen for the study, favored the NDD group (HR, 0.47; 95% CI, 0.27-0.81), but “this finding probably reflects a healthier cohort in the NDD group,” the investigators noted. Furthermore, “although the reason for the discrepancy in the composite outcome at 1 year is mainly driven by noncardiovascular readmission, other confounding variables cannot be entirely ruled out,” Dr. Kamioka and colleagues said in the report.
Predictors of NDD included male sex, no atrial fibrillation, lower serum creatinine level, and younger age, researchers also found.
A validation cohort would be needed to confirm the findings of this study, including predictors of favorable outcomes, and to apply NDD to a wider population, study authors said.
Dr. Kamioka reported no relationships relevant to the study. Study coauthors reported disclosures related to Edwards Lifesciences, Abbott Vascular, Medtronic, Gore Vascular, and Boston Scientific.
SOURCE: JACC: Cardiovascular Interventions. 2018 Jan 22. doi: 10.1016/j.jcin.2017.10.021.
FROM JACC: CARDIOVASCULAR INTERVENTIONS
Key clinical point: Next-day discharge (NDD) after minimalist TAVR appeared safe, compared with a longer hospital stay.
Major finding: The composite endpoint of mortality and readmission at 30 days was similar between groups (HR, 0.62; 95% CI, 0.20-1.91), and was lower in the NDD arm at 1 year because of fewer noncardiovascular readmissions.
Data source: A single-center, retrospective, nonrandomized observational analysis comprising 663 consecutive patients who underwent elective balloon-expandable TAVR between July 2014 and July 2016.
Disclosures: Study authors reported disclosures related to Edwards Lifesciences, Abbott Vascular, Medtronic, Gore Vascular, and Boston Scientific.
Source: JACC: Cardiovasc Interven. doi: 10.1016/j.jcin.2017.10.021.
Mogamulizumab active in HTLV-1–associated myelopathy
Mogamulizumab reduced the number of HTLV-1–infected cells and levels of inflammatory markers in patients with HTLV-1–associated myelopathy–tropical spastic paraparesis (HAM-TSP) in a recently reported phase 1-2a study.
Treatment with the anti-CCR4 monoclonal antibody also reduced spasticity and motor disability in some patients with HAM-TSP, according to results published in the New England Journal of Medicine.
Rash was the main side effect of treatment, but the 21-patient trial was “too small and too short to evaluate the clinical safety of mogamulizumab,” said lead author Tomoo Sato, MD, PhD, of the Department of Rare Diseases Research, St. Marianna University, Kawasaki, Japan, and colleagues.
HAM-TSP is a chronic, progressive, and debilitating neuroinflammatory disorder primarily seen in equatorial regions, according to the National Institute of Neurological Disorders and Stroke.
HTVL-1 infects primarily CCR4+ T cells, and mogamulizumab is an anti-CCR4 antibody that targets those affected cells, according to Dr. Sato and colleagues.
Current treatment for HAM-TSP is typically focused on suppressing inflammation with glucocorticoid or interferon-alpha rather than attacking infected cells and reducing proviral load.
The current investigator-initiated study included 21 patients with glucocorticoid-refractory HAM-TSP. In phase 1 of the study, patients received a single intravenous infusion of mogamulizumab and were observed for 85 days. Of those patients, 19 continued to phase 2a and received infusions at 8- or 12-week intervals for a total of 24 weeks.
Treatment resulted in a reduction of 64.9% (95% confidence interval, 51.7-78.1) in proviral load in peripheral-blood mononuclear cells by day 15 postinfusion. Reductions in inflammatory markers at day 29 were also reported, including a 37.3% decrease in CXCL10 levels and a 21.0% decrease in neopterin levels.
In all, 79% of patients had a reduction in spasticity, and 32% had decreased motor disability after treatment.
“The clinical effects appeared very quickly, long before any changes in the markers of inflammation in the central nervous system,” the investigators said.
Grade 1 or 2 rash was seen in 48% of patients, while lymphopenia and leukopenia were seen in 33% of patients each.
A phase 2 study is ongoing to evaluate the long-term safety and efficacy of mogamulizumab in patients with HAM-TSP.
The study was supported by the Japan Agency for Medical Research and Development and by the Ministry of Health, Labor, and Welfare. Two of the coauthors reported patents related to treating HTLV-I–related myelopathy.
SOURCE: Sato T et al. N Engl J Med. 2018;378:529-38.
Mogamulizumab reduced the number of HTLV-1–infected cells and levels of inflammatory markers in patients with HTLV-1–associated myelopathy–tropical spastic paraparesis (HAM-TSP) in a recently reported phase 1-2a study.
Treatment with the anti-CCR4 monoclonal antibody also reduced spasticity and motor disability in some patients with HAM-TSP, according to results published in the New England Journal of Medicine.
Rash was the main side effect of treatment, but the 21-patient trial was “too small and too short to evaluate the clinical safety of mogamulizumab,” said lead author Tomoo Sato, MD, PhD, of the Department of Rare Diseases Research, St. Marianna University, Kawasaki, Japan, and colleagues.
HAM-TSP is a chronic, progressive, and debilitating neuroinflammatory disorder primarily seen in equatorial regions, according to the National Institute of Neurological Disorders and Stroke.
HTVL-1 infects primarily CCR4+ T cells, and mogamulizumab is an anti-CCR4 antibody that targets those affected cells, according to Dr. Sato and colleagues.
Current treatment for HAM-TSP is typically focused on suppressing inflammation with glucocorticoid or interferon-alpha rather than attacking infected cells and reducing proviral load.
The current investigator-initiated study included 21 patients with glucocorticoid-refractory HAM-TSP. In phase 1 of the study, patients received a single intravenous infusion of mogamulizumab and were observed for 85 days. Of those patients, 19 continued to phase 2a and received infusions at 8- or 12-week intervals for a total of 24 weeks.
Treatment resulted in a reduction of 64.9% (95% confidence interval, 51.7-78.1) in proviral load in peripheral-blood mononuclear cells by day 15 postinfusion. Reductions in inflammatory markers at day 29 were also reported, including a 37.3% decrease in CXCL10 levels and a 21.0% decrease in neopterin levels.
In all, 79% of patients had a reduction in spasticity, and 32% had decreased motor disability after treatment.
“The clinical effects appeared very quickly, long before any changes in the markers of inflammation in the central nervous system,” the investigators said.
Grade 1 or 2 rash was seen in 48% of patients, while lymphopenia and leukopenia were seen in 33% of patients each.
A phase 2 study is ongoing to evaluate the long-term safety and efficacy of mogamulizumab in patients with HAM-TSP.
The study was supported by the Japan Agency for Medical Research and Development and by the Ministry of Health, Labor, and Welfare. Two of the coauthors reported patents related to treating HTLV-I–related myelopathy.
SOURCE: Sato T et al. N Engl J Med. 2018;378:529-38.
Mogamulizumab reduced the number of HTLV-1–infected cells and levels of inflammatory markers in patients with HTLV-1–associated myelopathy–tropical spastic paraparesis (HAM-TSP) in a recently reported phase 1-2a study.
Treatment with the anti-CCR4 monoclonal antibody also reduced spasticity and motor disability in some patients with HAM-TSP, according to results published in the New England Journal of Medicine.
Rash was the main side effect of treatment, but the 21-patient trial was “too small and too short to evaluate the clinical safety of mogamulizumab,” said lead author Tomoo Sato, MD, PhD, of the Department of Rare Diseases Research, St. Marianna University, Kawasaki, Japan, and colleagues.
HAM-TSP is a chronic, progressive, and debilitating neuroinflammatory disorder primarily seen in equatorial regions, according to the National Institute of Neurological Disorders and Stroke.
HTVL-1 infects primarily CCR4+ T cells, and mogamulizumab is an anti-CCR4 antibody that targets those affected cells, according to Dr. Sato and colleagues.
Current treatment for HAM-TSP is typically focused on suppressing inflammation with glucocorticoid or interferon-alpha rather than attacking infected cells and reducing proviral load.
The current investigator-initiated study included 21 patients with glucocorticoid-refractory HAM-TSP. In phase 1 of the study, patients received a single intravenous infusion of mogamulizumab and were observed for 85 days. Of those patients, 19 continued to phase 2a and received infusions at 8- or 12-week intervals for a total of 24 weeks.
Treatment resulted in a reduction of 64.9% (95% confidence interval, 51.7-78.1) in proviral load in peripheral-blood mononuclear cells by day 15 postinfusion. Reductions in inflammatory markers at day 29 were also reported, including a 37.3% decrease in CXCL10 levels and a 21.0% decrease in neopterin levels.
In all, 79% of patients had a reduction in spasticity, and 32% had decreased motor disability after treatment.
“The clinical effects appeared very quickly, long before any changes in the markers of inflammation in the central nervous system,” the investigators said.
Grade 1 or 2 rash was seen in 48% of patients, while lymphopenia and leukopenia were seen in 33% of patients each.
A phase 2 study is ongoing to evaluate the long-term safety and efficacy of mogamulizumab in patients with HAM-TSP.
The study was supported by the Japan Agency for Medical Research and Development and by the Ministry of Health, Labor, and Welfare. Two of the coauthors reported patents related to treating HTLV-I–related myelopathy.
SOURCE: Sato T et al. N Engl J Med. 2018;378:529-38.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Investigators reported a 64.9% reduction in proviral load by day 15 postinfusion and reductions in inflammatory markers by day 29.
Study details: An investigator-initiated, uncontrolled phase 1-2a study of mogamulizumab in 21 patients with glucocorticoid-refractory HAM-TSP.
Disclosures: The study was supported by the Japan Agency for Medical Research and Development and by the Ministry of Health, Labor, and Welfare. Two of the coauthors reported patents related to treating HTLV-I–related myelopathy.
Source: Sato T et al. N Engl J Med. 2018;378:529-38.
ASCO expands recommendations on bone-modifying agents in myeloma
Bisphosphonates should be prescribed for any patient receiving treatment for active multiple myeloma, regardless of whether or not there is evidence of lytic bone destruction or spinal compression fracture, according to updated guidelines from the American Society of Clinical Oncology.
Previous guidelines from the society, last updated in 2007, recommended the use of intravenous bisphosphonates for patients with myeloma with evidence of bone disease, according to the expert panel that drafted the update.
“Fewer adverse events related to renal toxicity have been noted with denosumab, compared with zoledronic acid,” and “this may be preferred in patients with compromised renal function,” wrote the expert panel, led by cochairs Kenneth C. Anderson, MD, of Dana-Farber Cancer Institute, Boston, and Robert A. Kyle, MD, of Mayo Clinic, Rochester, Minn.
ASCO guidelines on bisphosphonates in myeloma were first drafted in 2002 and then updated in 2007. The new recommendations on bone-modifying therapy in myeloma are based on review of an additional 35 publications. The new guidelines are “consistent with the previous recommendations” while updating indications for therapy and information on denosumab, according to the expert panel.
Evidence that myeloma patients without lytic bone disease will benefit from intravenous bisphosphonates comes from the randomized MRC IX trial, in which patients who received zoledronic acid had reduced skeletal-related events at relapse and improved progression-free survival.
Denosumab, a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor, was noninferior to zoledronic acid for prevention of skeletal-related events in a randomized phase 3 clinical trial; however, it is “more expensive than zoledronic acid or pamidronate and must be considered in treatment decisions,” the guidelines authors wrote.
The total price in the United States for a 1-year treatment cycle of denosumab is just under $26,000, according to data included in the ASCO guideline. By comparison, the 1-year treatment cycle price for the bisphosphonates ranges from $214 to $697, depending on the regimen.
When intravenous bisphosphonate therapy is warranted, the guideline-recommended schedule is infusion of zoledronic acid 4 mg over at least 15 minutes, or pamidronate 90 mg over 2 hours, every 3-4 weeks.
The guidelines also address osteonecrosis of the jaw (ONJ), a major complication observed not only with the potent bisphosphonates pamidronate and zoledronic acid, but also with denosumab.
The panel said they were in agreement with revised labels from the Food and Drug Administration for zoledronic acid and pamidronate, among other papers or statements addressing ONJ and noted that patients need a comprehensive dental exam and preventive dentistry as appropriate before starting bone-modifying therapy.
“The risk of ONJ has prompted the use of less-frequent dosing of zoledronic acid, which may be an option for patients,” they said in their report.
Guideline authors reported ties to Amgen, Celgene, Millennium Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, Novartis, Pfizer, and others.
SOURCE: Anderson K et al. J Clin Oncol. 2018 Jan 17:JCO2017766402. doi: 10.1200/JCO.2017.76.6402.
Bisphosphonates should be prescribed for any patient receiving treatment for active multiple myeloma, regardless of whether or not there is evidence of lytic bone destruction or spinal compression fracture, according to updated guidelines from the American Society of Clinical Oncology.
Previous guidelines from the society, last updated in 2007, recommended the use of intravenous bisphosphonates for patients with myeloma with evidence of bone disease, according to the expert panel that drafted the update.
“Fewer adverse events related to renal toxicity have been noted with denosumab, compared with zoledronic acid,” and “this may be preferred in patients with compromised renal function,” wrote the expert panel, led by cochairs Kenneth C. Anderson, MD, of Dana-Farber Cancer Institute, Boston, and Robert A. Kyle, MD, of Mayo Clinic, Rochester, Minn.
ASCO guidelines on bisphosphonates in myeloma were first drafted in 2002 and then updated in 2007. The new recommendations on bone-modifying therapy in myeloma are based on review of an additional 35 publications. The new guidelines are “consistent with the previous recommendations” while updating indications for therapy and information on denosumab, according to the expert panel.
Evidence that myeloma patients without lytic bone disease will benefit from intravenous bisphosphonates comes from the randomized MRC IX trial, in which patients who received zoledronic acid had reduced skeletal-related events at relapse and improved progression-free survival.
Denosumab, a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor, was noninferior to zoledronic acid for prevention of skeletal-related events in a randomized phase 3 clinical trial; however, it is “more expensive than zoledronic acid or pamidronate and must be considered in treatment decisions,” the guidelines authors wrote.
The total price in the United States for a 1-year treatment cycle of denosumab is just under $26,000, according to data included in the ASCO guideline. By comparison, the 1-year treatment cycle price for the bisphosphonates ranges from $214 to $697, depending on the regimen.
When intravenous bisphosphonate therapy is warranted, the guideline-recommended schedule is infusion of zoledronic acid 4 mg over at least 15 minutes, or pamidronate 90 mg over 2 hours, every 3-4 weeks.
The guidelines also address osteonecrosis of the jaw (ONJ), a major complication observed not only with the potent bisphosphonates pamidronate and zoledronic acid, but also with denosumab.
The panel said they were in agreement with revised labels from the Food and Drug Administration for zoledronic acid and pamidronate, among other papers or statements addressing ONJ and noted that patients need a comprehensive dental exam and preventive dentistry as appropriate before starting bone-modifying therapy.
“The risk of ONJ has prompted the use of less-frequent dosing of zoledronic acid, which may be an option for patients,” they said in their report.
Guideline authors reported ties to Amgen, Celgene, Millennium Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, Novartis, Pfizer, and others.
SOURCE: Anderson K et al. J Clin Oncol. 2018 Jan 17:JCO2017766402. doi: 10.1200/JCO.2017.76.6402.
Bisphosphonates should be prescribed for any patient receiving treatment for active multiple myeloma, regardless of whether or not there is evidence of lytic bone destruction or spinal compression fracture, according to updated guidelines from the American Society of Clinical Oncology.
Previous guidelines from the society, last updated in 2007, recommended the use of intravenous bisphosphonates for patients with myeloma with evidence of bone disease, according to the expert panel that drafted the update.
“Fewer adverse events related to renal toxicity have been noted with denosumab, compared with zoledronic acid,” and “this may be preferred in patients with compromised renal function,” wrote the expert panel, led by cochairs Kenneth C. Anderson, MD, of Dana-Farber Cancer Institute, Boston, and Robert A. Kyle, MD, of Mayo Clinic, Rochester, Minn.
ASCO guidelines on bisphosphonates in myeloma were first drafted in 2002 and then updated in 2007. The new recommendations on bone-modifying therapy in myeloma are based on review of an additional 35 publications. The new guidelines are “consistent with the previous recommendations” while updating indications for therapy and information on denosumab, according to the expert panel.
Evidence that myeloma patients without lytic bone disease will benefit from intravenous bisphosphonates comes from the randomized MRC IX trial, in which patients who received zoledronic acid had reduced skeletal-related events at relapse and improved progression-free survival.
Denosumab, a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor, was noninferior to zoledronic acid for prevention of skeletal-related events in a randomized phase 3 clinical trial; however, it is “more expensive than zoledronic acid or pamidronate and must be considered in treatment decisions,” the guidelines authors wrote.
The total price in the United States for a 1-year treatment cycle of denosumab is just under $26,000, according to data included in the ASCO guideline. By comparison, the 1-year treatment cycle price for the bisphosphonates ranges from $214 to $697, depending on the regimen.
When intravenous bisphosphonate therapy is warranted, the guideline-recommended schedule is infusion of zoledronic acid 4 mg over at least 15 minutes, or pamidronate 90 mg over 2 hours, every 3-4 weeks.
The guidelines also address osteonecrosis of the jaw (ONJ), a major complication observed not only with the potent bisphosphonates pamidronate and zoledronic acid, but also with denosumab.
The panel said they were in agreement with revised labels from the Food and Drug Administration for zoledronic acid and pamidronate, among other papers or statements addressing ONJ and noted that patients need a comprehensive dental exam and preventive dentistry as appropriate before starting bone-modifying therapy.
“The risk of ONJ has prompted the use of less-frequent dosing of zoledronic acid, which may be an option for patients,” they said in their report.
Guideline authors reported ties to Amgen, Celgene, Millennium Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, Novartis, Pfizer, and others.
SOURCE: Anderson K et al. J Clin Oncol. 2018 Jan 17:JCO2017766402. doi: 10.1200/JCO.2017.76.6402.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
AHA: Heart health helps optimize breast cancer outcomes
Breast cancer outcomes rely on “coexisting cardiovascular health” at every step in the patient journey, the American Heart Association has said in its first-ever scientific statement on the matter.
The statement, published in Circulation provides a comprehensive overview of cardiovascular disease and breast cancer prevalence and shared risk factors, as well as current recommendations on avoiding the cardiotoxic effects of some cancer treatments and strategies to prevent or treat CVD in breast cancer patients.
Cardiovascular disease and breast cancer are two entities that are frequently intertwined, Laxmi S. Mehta, MD, chair of the statement writing group, said in an interview.
“For any oncologic patient, it’s important to also consider their heart in the risk assessment because that also affects survival from the cancer,” said Dr. Mehta, the director of the Women’s Cardiovascular Health Program and an associate professor of medicine at the Ohio State University, Columbus.
Mortality risk attributable to CVD is higher in breast cancer survivors than in women who have no history of breast cancer, according to evidence Dr. Mehta and her colleagues cite in the statement.
Breast cancer and CVD share a number of common and sometimes modifiable risk factors, including dietary patterns, physical activity, and being overweight or obese, and tobacco use. There is “growing awareness” that modifying those risk factors may help prevent some cases of breast cancer.
Even in patients who have a breast cancer diagnosis, “from a cardiology standpoint, lifestyle is going to be key,” said Dr. Mehta. She said breast cancer patients can be encouraged to follow AHA recommendations to aim for 150 minutes of moderate aerobic exercise weekly and to follow an “overall healthy dietary pattern” that limits saturated and trans fats, sodium, red meat, sweets, and sugar-sweetened beverages.
Although left ventricular systolic dysfunction is the most common cardiovascular side effect associated with chemotherapy, other manifestations of early or delayed cardiotoxicity can include heart failure, hypertension, thromboembolic disease, pulmonary hypertension, pericarditis, and myocardial ischemia, according to the AHA scientific statement.
A wide range of standard breast cancer treatments cause cardiovascular adverse effects, including taxanes such as paclitaxel, anthracyclines such as doxorubicin, and alkylating agents such as cisplatin and cyclophosphamide, as outlined in the statement.
Targeted HER-2–directed therapies, including trastuzumab and pertuzumab, are associated with left ventricular dysfunction and heart failure, while emerging therapies, such as the cyclin-dependent kinase 4/6 inhibitors palbociclib and ribociclib, are associated with QTc prolongation, the statement also notes.
Current strategies for monitoring for cardiovascular toxicity, which typically involve myocardial strain imaging, assessing cardiac biomarkers, or a combination of imaging and biomarkers, are outlined in the report.
To mitigate the impact of cancer treatments on cardiovascular health, several oncologic strategies are useful, according to Dr. Mehta and colleagues.
In multiple clinical trials of breast cancer patients receiving doxorubicin or epirubicin, the iron-binding agent dexrazoxane reduced the combined endpoint of decreased left ventricular ejection fraction or development of heart failure, the authors said.
Likewise, clinical trial evidence has suggested cardiotoxicity associated with doxorubicin can be mitigated through administration via infusion as opposed to bolus and with longer versus shorter infusion durations, they continued.
Extreme cases or difficult-to-manage patients can be referred to a center that has an active program in cardio-oncology, a newer and rapidly expanding field, according to Dr. Mehta.
“That’s where there’s tight collaboration in terms of understanding the current treatments, and that’s also where research on how to best take care of these patients will be conducted,” she said.
Dr. Mehta reported no disclosures. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Genentech, AstraZeneca, Lilly, Roche, Novartis, and others.
SOURCE: Mehta LS et al. Circulation. 2017 Jan 22. doi: 10.1161/CIR.0000000000000556.
Breast cancer outcomes rely on “coexisting cardiovascular health” at every step in the patient journey, the American Heart Association has said in its first-ever scientific statement on the matter.
The statement, published in Circulation provides a comprehensive overview of cardiovascular disease and breast cancer prevalence and shared risk factors, as well as current recommendations on avoiding the cardiotoxic effects of some cancer treatments and strategies to prevent or treat CVD in breast cancer patients.
Cardiovascular disease and breast cancer are two entities that are frequently intertwined, Laxmi S. Mehta, MD, chair of the statement writing group, said in an interview.
“For any oncologic patient, it’s important to also consider their heart in the risk assessment because that also affects survival from the cancer,” said Dr. Mehta, the director of the Women’s Cardiovascular Health Program and an associate professor of medicine at the Ohio State University, Columbus.
Mortality risk attributable to CVD is higher in breast cancer survivors than in women who have no history of breast cancer, according to evidence Dr. Mehta and her colleagues cite in the statement.
Breast cancer and CVD share a number of common and sometimes modifiable risk factors, including dietary patterns, physical activity, and being overweight or obese, and tobacco use. There is “growing awareness” that modifying those risk factors may help prevent some cases of breast cancer.
Even in patients who have a breast cancer diagnosis, “from a cardiology standpoint, lifestyle is going to be key,” said Dr. Mehta. She said breast cancer patients can be encouraged to follow AHA recommendations to aim for 150 minutes of moderate aerobic exercise weekly and to follow an “overall healthy dietary pattern” that limits saturated and trans fats, sodium, red meat, sweets, and sugar-sweetened beverages.
Although left ventricular systolic dysfunction is the most common cardiovascular side effect associated with chemotherapy, other manifestations of early or delayed cardiotoxicity can include heart failure, hypertension, thromboembolic disease, pulmonary hypertension, pericarditis, and myocardial ischemia, according to the AHA scientific statement.
A wide range of standard breast cancer treatments cause cardiovascular adverse effects, including taxanes such as paclitaxel, anthracyclines such as doxorubicin, and alkylating agents such as cisplatin and cyclophosphamide, as outlined in the statement.
Targeted HER-2–directed therapies, including trastuzumab and pertuzumab, are associated with left ventricular dysfunction and heart failure, while emerging therapies, such as the cyclin-dependent kinase 4/6 inhibitors palbociclib and ribociclib, are associated with QTc prolongation, the statement also notes.
Current strategies for monitoring for cardiovascular toxicity, which typically involve myocardial strain imaging, assessing cardiac biomarkers, or a combination of imaging and biomarkers, are outlined in the report.
To mitigate the impact of cancer treatments on cardiovascular health, several oncologic strategies are useful, according to Dr. Mehta and colleagues.
In multiple clinical trials of breast cancer patients receiving doxorubicin or epirubicin, the iron-binding agent dexrazoxane reduced the combined endpoint of decreased left ventricular ejection fraction or development of heart failure, the authors said.
Likewise, clinical trial evidence has suggested cardiotoxicity associated with doxorubicin can be mitigated through administration via infusion as opposed to bolus and with longer versus shorter infusion durations, they continued.
Extreme cases or difficult-to-manage patients can be referred to a center that has an active program in cardio-oncology, a newer and rapidly expanding field, according to Dr. Mehta.
“That’s where there’s tight collaboration in terms of understanding the current treatments, and that’s also where research on how to best take care of these patients will be conducted,” she said.
Dr. Mehta reported no disclosures. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Genentech, AstraZeneca, Lilly, Roche, Novartis, and others.
SOURCE: Mehta LS et al. Circulation. 2017 Jan 22. doi: 10.1161/CIR.0000000000000556.
Breast cancer outcomes rely on “coexisting cardiovascular health” at every step in the patient journey, the American Heart Association has said in its first-ever scientific statement on the matter.
The statement, published in Circulation provides a comprehensive overview of cardiovascular disease and breast cancer prevalence and shared risk factors, as well as current recommendations on avoiding the cardiotoxic effects of some cancer treatments and strategies to prevent or treat CVD in breast cancer patients.
Cardiovascular disease and breast cancer are two entities that are frequently intertwined, Laxmi S. Mehta, MD, chair of the statement writing group, said in an interview.
“For any oncologic patient, it’s important to also consider their heart in the risk assessment because that also affects survival from the cancer,” said Dr. Mehta, the director of the Women’s Cardiovascular Health Program and an associate professor of medicine at the Ohio State University, Columbus.
Mortality risk attributable to CVD is higher in breast cancer survivors than in women who have no history of breast cancer, according to evidence Dr. Mehta and her colleagues cite in the statement.
Breast cancer and CVD share a number of common and sometimes modifiable risk factors, including dietary patterns, physical activity, and being overweight or obese, and tobacco use. There is “growing awareness” that modifying those risk factors may help prevent some cases of breast cancer.
Even in patients who have a breast cancer diagnosis, “from a cardiology standpoint, lifestyle is going to be key,” said Dr. Mehta. She said breast cancer patients can be encouraged to follow AHA recommendations to aim for 150 minutes of moderate aerobic exercise weekly and to follow an “overall healthy dietary pattern” that limits saturated and trans fats, sodium, red meat, sweets, and sugar-sweetened beverages.
Although left ventricular systolic dysfunction is the most common cardiovascular side effect associated with chemotherapy, other manifestations of early or delayed cardiotoxicity can include heart failure, hypertension, thromboembolic disease, pulmonary hypertension, pericarditis, and myocardial ischemia, according to the AHA scientific statement.
A wide range of standard breast cancer treatments cause cardiovascular adverse effects, including taxanes such as paclitaxel, anthracyclines such as doxorubicin, and alkylating agents such as cisplatin and cyclophosphamide, as outlined in the statement.
Targeted HER-2–directed therapies, including trastuzumab and pertuzumab, are associated with left ventricular dysfunction and heart failure, while emerging therapies, such as the cyclin-dependent kinase 4/6 inhibitors palbociclib and ribociclib, are associated with QTc prolongation, the statement also notes.
Current strategies for monitoring for cardiovascular toxicity, which typically involve myocardial strain imaging, assessing cardiac biomarkers, or a combination of imaging and biomarkers, are outlined in the report.
To mitigate the impact of cancer treatments on cardiovascular health, several oncologic strategies are useful, according to Dr. Mehta and colleagues.
In multiple clinical trials of breast cancer patients receiving doxorubicin or epirubicin, the iron-binding agent dexrazoxane reduced the combined endpoint of decreased left ventricular ejection fraction or development of heart failure, the authors said.
Likewise, clinical trial evidence has suggested cardiotoxicity associated with doxorubicin can be mitigated through administration via infusion as opposed to bolus and with longer versus shorter infusion durations, they continued.
Extreme cases or difficult-to-manage patients can be referred to a center that has an active program in cardio-oncology, a newer and rapidly expanding field, according to Dr. Mehta.
“That’s where there’s tight collaboration in terms of understanding the current treatments, and that’s also where research on how to best take care of these patients will be conducted,” she said.
Dr. Mehta reported no disclosures. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Genentech, AstraZeneca, Lilly, Roche, Novartis, and others.
SOURCE: Mehta LS et al. Circulation. 2017 Jan 22. doi: 10.1161/CIR.0000000000000556.
FROM CIRCULATION
CAR T cells produce longest survival in low disease burden ALL patients
Among patients with B-cell acute lymphoblastic leukemia (ALL) who received an infusion of 19-28z CAR T cells, patients with low disease burden had better survival outcomes and fewer toxic effects than did patients with a high disease burden, according to long-term follow-up results of a phase 1 study.
Median overall survival for B-cell ALL patients with low disease burden was 20.1 months, compared with 12.4 months for those with a high disease burden (P = .02), and 12.9 months for the entire cohort, according to results published in the New England Journal of Medicine.
The 12.9-month overall survival for the full study cohort “compares favorably” to results from another recently reported clinical trial showing overall survival of 7.7 months for adult B-cell ALL patients treated with blinatumomab, an anti–CD19/CD3 bispecific T-cell engager, wrote Jae H. Park, MD, of the Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, and his coauthors.
The CAR T-cell and blinatumomab results cannot be directly compared owing to the differences in study design, patient characteristics, and posttreatment consolidation, but “the observation of patients with durable remissions in these two studies highlights the potential of CD19-targeted immunotherapies,” Dr. Park and his colleagues wrote in their report.
The phase 1 trial by Dr. Park and his colleagues included 53 adults with relapsed B-cell ALL who received a single infusion of 19-28z CAR T-cell therapy manufactured at Memorial Sloan Kettering Cancer Center.
After the infusion, 41% of patients with high disease burden (at least 5% bone marrow blasts or extramedullary disease) experienced severe cytokine release syndrome, compared with 5% of those with low disease burden, according to the report.
Likewise, neurotoxic effects were seen in 59% of high disease burden B-ALL patients, compared with 14% of those with low disease burden, the investigators reported.
Low disease burden was associated with a higher rate of complete remission, but this finding did not reach statistical significance. However, low disease burden patients not only had improved overall survival, as noted, but also had a significantly longer event-free survival versus high disease burden patients (10.6 and 5.3 months, respectively; P = .01).
Robust expansion of CAR T cells in vivo was a good predictor of short-term response and toxic effects but did not correlate with longer-term efficacy, according to the researchers. Instead, the ratio of peak CAR T-cell expansion to tumor burden correlated significantly with event-free and overall survival.
That finding “raises the hypothesis that an effective ratio of CAR T cells to target CD19+ leukemia cells is more likely to occur in patients with a low disease burden than in those with a high disease burden, despite a smaller number of expanded T cells in patients with a low disease burden,” the investigators wrote.
The study was funded by the Commonwealth Foundation for Cancer Research, Juno Therapeutics, and others. Several study authors reported ties to Juno Therapeutics and other pharmaceutical companies.
SOURCE: Park JH et al. N Engl J Med 2018 Feb 1;378:449-59.
Among patients with B-cell acute lymphoblastic leukemia (ALL) who received an infusion of 19-28z CAR T cells, patients with low disease burden had better survival outcomes and fewer toxic effects than did patients with a high disease burden, according to long-term follow-up results of a phase 1 study.
Median overall survival for B-cell ALL patients with low disease burden was 20.1 months, compared with 12.4 months for those with a high disease burden (P = .02), and 12.9 months for the entire cohort, according to results published in the New England Journal of Medicine.
The 12.9-month overall survival for the full study cohort “compares favorably” to results from another recently reported clinical trial showing overall survival of 7.7 months for adult B-cell ALL patients treated with blinatumomab, an anti–CD19/CD3 bispecific T-cell engager, wrote Jae H. Park, MD, of the Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, and his coauthors.
The CAR T-cell and blinatumomab results cannot be directly compared owing to the differences in study design, patient characteristics, and posttreatment consolidation, but “the observation of patients with durable remissions in these two studies highlights the potential of CD19-targeted immunotherapies,” Dr. Park and his colleagues wrote in their report.
The phase 1 trial by Dr. Park and his colleagues included 53 adults with relapsed B-cell ALL who received a single infusion of 19-28z CAR T-cell therapy manufactured at Memorial Sloan Kettering Cancer Center.
After the infusion, 41% of patients with high disease burden (at least 5% bone marrow blasts or extramedullary disease) experienced severe cytokine release syndrome, compared with 5% of those with low disease burden, according to the report.
Likewise, neurotoxic effects were seen in 59% of high disease burden B-ALL patients, compared with 14% of those with low disease burden, the investigators reported.
Low disease burden was associated with a higher rate of complete remission, but this finding did not reach statistical significance. However, low disease burden patients not only had improved overall survival, as noted, but also had a significantly longer event-free survival versus high disease burden patients (10.6 and 5.3 months, respectively; P = .01).
Robust expansion of CAR T cells in vivo was a good predictor of short-term response and toxic effects but did not correlate with longer-term efficacy, according to the researchers. Instead, the ratio of peak CAR T-cell expansion to tumor burden correlated significantly with event-free and overall survival.
That finding “raises the hypothesis that an effective ratio of CAR T cells to target CD19+ leukemia cells is more likely to occur in patients with a low disease burden than in those with a high disease burden, despite a smaller number of expanded T cells in patients with a low disease burden,” the investigators wrote.
The study was funded by the Commonwealth Foundation for Cancer Research, Juno Therapeutics, and others. Several study authors reported ties to Juno Therapeutics and other pharmaceutical companies.
SOURCE: Park JH et al. N Engl J Med 2018 Feb 1;378:449-59.
Among patients with B-cell acute lymphoblastic leukemia (ALL) who received an infusion of 19-28z CAR T cells, patients with low disease burden had better survival outcomes and fewer toxic effects than did patients with a high disease burden, according to long-term follow-up results of a phase 1 study.
Median overall survival for B-cell ALL patients with low disease burden was 20.1 months, compared with 12.4 months for those with a high disease burden (P = .02), and 12.9 months for the entire cohort, according to results published in the New England Journal of Medicine.
The 12.9-month overall survival for the full study cohort “compares favorably” to results from another recently reported clinical trial showing overall survival of 7.7 months for adult B-cell ALL patients treated with blinatumomab, an anti–CD19/CD3 bispecific T-cell engager, wrote Jae H. Park, MD, of the Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, and his coauthors.
The CAR T-cell and blinatumomab results cannot be directly compared owing to the differences in study design, patient characteristics, and posttreatment consolidation, but “the observation of patients with durable remissions in these two studies highlights the potential of CD19-targeted immunotherapies,” Dr. Park and his colleagues wrote in their report.
The phase 1 trial by Dr. Park and his colleagues included 53 adults with relapsed B-cell ALL who received a single infusion of 19-28z CAR T-cell therapy manufactured at Memorial Sloan Kettering Cancer Center.
After the infusion, 41% of patients with high disease burden (at least 5% bone marrow blasts or extramedullary disease) experienced severe cytokine release syndrome, compared with 5% of those with low disease burden, according to the report.
Likewise, neurotoxic effects were seen in 59% of high disease burden B-ALL patients, compared with 14% of those with low disease burden, the investigators reported.
Low disease burden was associated with a higher rate of complete remission, but this finding did not reach statistical significance. However, low disease burden patients not only had improved overall survival, as noted, but also had a significantly longer event-free survival versus high disease burden patients (10.6 and 5.3 months, respectively; P = .01).
Robust expansion of CAR T cells in vivo was a good predictor of short-term response and toxic effects but did not correlate with longer-term efficacy, according to the researchers. Instead, the ratio of peak CAR T-cell expansion to tumor burden correlated significantly with event-free and overall survival.
That finding “raises the hypothesis that an effective ratio of CAR T cells to target CD19+ leukemia cells is more likely to occur in patients with a low disease burden than in those with a high disease burden, despite a smaller number of expanded T cells in patients with a low disease burden,” the investigators wrote.
The study was funded by the Commonwealth Foundation for Cancer Research, Juno Therapeutics, and others. Several study authors reported ties to Juno Therapeutics and other pharmaceutical companies.
SOURCE: Park JH et al. N Engl J Med 2018 Feb 1;378:449-59.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Median overall survival for patients with low disease burden was 20.1 months, compared with 12.4 months for those with a high disease burden (P = .02).
Study details: A long-term follow-up of a phase 1 trial including 53 adults with relapsed B-cell ALL.
Disclosures: The study was funded by the Commonwealth Foundation for Cancer Research, Juno Therapeutics, and others. Several study authors reported ties to Juno Therapeutics and other pharmaceutical companies.
Source: Park JH et al. N Engl J Med 2018 Feb 1;378:449-59.
Contaminated graft causes infection in ALL patient
, according to a letter to the editor published in Infection Control & Hospital Epidemiology.
Strains of Staphylococcus aureus found in isolates from the HSC graft and the patient were confirmed to be identical using pulsed-field gel electrophoresis, the authors, led by Zachary I. Willis, MD, MPH, of the department of pediatrics at the University of North Carolina at Chapel Hill, said.
“While multiple reports have found that low-grade bacterial contamination of HSC products is rarely consequential, our patient’s experience demonstrated that clinically significant infections may occur,” Dr. Willis and his colleagues wrote in the case report.
When less virulent organisms are found in HSC grafts, close observation may be warranted, the investigators said; however, a more aggressive approach might be considered when more virulent organisms are found.
“In such a case, we suggest obtaining blood cultures and considering preemptive antibiotics as guided by the identity and susceptibility of the contaminating organism,” the investigators wrote.
Dr. Willis and his colleagues reported the case of a 15-year-old boy with hypodiploid B-ALL who achieved complete remission after treatment and then underwent a 10/10 HLA allele–matched unrelated donor hematopoietic cell transplant.
The patient developed a fever of 38.3º C with tachycardia but no other sepsis signs approximately 24 hours after the transplant. Soon afterward, the care team was informed that there was a single colony each of Micrococcus and S. aureus in the culture of the HSC product. Methicillin susceptibility was later confirmed. Antibiotic treatment was changed accordingly, and as of 117 days post transplant, the patient was “doing well with no evidence of further infectious complications,” the investigators said.
Bacterial contamination of HSC grafts is relatively common, with reported rates ranging from 1% to 45%. However, the clinical significance of the contamination has been unclear. Moreover, contamination is not an absolute contraindication to infusion, as options for the patient are limited after a myeloablative preparative regimen.
There are some previous case reports also identifying infections caused by contaminated grafts, but in those cases, the evidence linking the graft to the infection was based solely on finding identical species, while in the present report, the graft and patient isolates were confirmed to be identical using pulsed-field gel electrophoresis.
The investigators reported having no outside funding and no financial disclosures.
SOURCE: Willis Z et al, Infect Control Hosp Epidemiol. 2018 Jan 23. doi: 10.1017/ice.2017.285.
, according to a letter to the editor published in Infection Control & Hospital Epidemiology.
Strains of Staphylococcus aureus found in isolates from the HSC graft and the patient were confirmed to be identical using pulsed-field gel electrophoresis, the authors, led by Zachary I. Willis, MD, MPH, of the department of pediatrics at the University of North Carolina at Chapel Hill, said.
“While multiple reports have found that low-grade bacterial contamination of HSC products is rarely consequential, our patient’s experience demonstrated that clinically significant infections may occur,” Dr. Willis and his colleagues wrote in the case report.
When less virulent organisms are found in HSC grafts, close observation may be warranted, the investigators said; however, a more aggressive approach might be considered when more virulent organisms are found.
“In such a case, we suggest obtaining blood cultures and considering preemptive antibiotics as guided by the identity and susceptibility of the contaminating organism,” the investigators wrote.
Dr. Willis and his colleagues reported the case of a 15-year-old boy with hypodiploid B-ALL who achieved complete remission after treatment and then underwent a 10/10 HLA allele–matched unrelated donor hematopoietic cell transplant.
The patient developed a fever of 38.3º C with tachycardia but no other sepsis signs approximately 24 hours after the transplant. Soon afterward, the care team was informed that there was a single colony each of Micrococcus and S. aureus in the culture of the HSC product. Methicillin susceptibility was later confirmed. Antibiotic treatment was changed accordingly, and as of 117 days post transplant, the patient was “doing well with no evidence of further infectious complications,” the investigators said.
Bacterial contamination of HSC grafts is relatively common, with reported rates ranging from 1% to 45%. However, the clinical significance of the contamination has been unclear. Moreover, contamination is not an absolute contraindication to infusion, as options for the patient are limited after a myeloablative preparative regimen.
There are some previous case reports also identifying infections caused by contaminated grafts, but in those cases, the evidence linking the graft to the infection was based solely on finding identical species, while in the present report, the graft and patient isolates were confirmed to be identical using pulsed-field gel electrophoresis.
The investigators reported having no outside funding and no financial disclosures.
SOURCE: Willis Z et al, Infect Control Hosp Epidemiol. 2018 Jan 23. doi: 10.1017/ice.2017.285.
, according to a letter to the editor published in Infection Control & Hospital Epidemiology.
Strains of Staphylococcus aureus found in isolates from the HSC graft and the patient were confirmed to be identical using pulsed-field gel electrophoresis, the authors, led by Zachary I. Willis, MD, MPH, of the department of pediatrics at the University of North Carolina at Chapel Hill, said.
“While multiple reports have found that low-grade bacterial contamination of HSC products is rarely consequential, our patient’s experience demonstrated that clinically significant infections may occur,” Dr. Willis and his colleagues wrote in the case report.
When less virulent organisms are found in HSC grafts, close observation may be warranted, the investigators said; however, a more aggressive approach might be considered when more virulent organisms are found.
“In such a case, we suggest obtaining blood cultures and considering preemptive antibiotics as guided by the identity and susceptibility of the contaminating organism,” the investigators wrote.
Dr. Willis and his colleagues reported the case of a 15-year-old boy with hypodiploid B-ALL who achieved complete remission after treatment and then underwent a 10/10 HLA allele–matched unrelated donor hematopoietic cell transplant.
The patient developed a fever of 38.3º C with tachycardia but no other sepsis signs approximately 24 hours after the transplant. Soon afterward, the care team was informed that there was a single colony each of Micrococcus and S. aureus in the culture of the HSC product. Methicillin susceptibility was later confirmed. Antibiotic treatment was changed accordingly, and as of 117 days post transplant, the patient was “doing well with no evidence of further infectious complications,” the investigators said.
Bacterial contamination of HSC grafts is relatively common, with reported rates ranging from 1% to 45%. However, the clinical significance of the contamination has been unclear. Moreover, contamination is not an absolute contraindication to infusion, as options for the patient are limited after a myeloablative preparative regimen.
There are some previous case reports also identifying infections caused by contaminated grafts, but in those cases, the evidence linking the graft to the infection was based solely on finding identical species, while in the present report, the graft and patient isolates were confirmed to be identical using pulsed-field gel electrophoresis.
The investigators reported having no outside funding and no financial disclosures.
SOURCE: Willis Z et al, Infect Control Hosp Epidemiol. 2018 Jan 23. doi: 10.1017/ice.2017.285.
FROM INFECTION CONTROL & HOSPITAL EPIDEMIOLOGY
Letrozole promising as maintenance treatment for high-grade serous ovarian cancer
Maintenance therapy with an aromatase inhibitor may improve progression-free survival in women with estrogen receptor (ER)–positive, high-grade serous ovarian cancers, results of a non-randomized, single-center study suggest.
Patients who received compared with patients who declined the treatment, investigators reported in Gynecologic Oncology.
The benefit of letrozole maintenance treatment was also apparent in women with residual disease who received bevacizumab maintenance treatment, wrote first author Viola Heinzelmann-Schwarz, MD, of the Gynecological Cancer Center, University of Basel, Switzerland, and her coauthors.
The results “strongly suggest that endocrine maintenance therapy has more advantage than disadvantage for use in ovarian cancer patients and seems clearly justified,” when considered alongside other data regarding the potential benefit of letrozole in other treatment settings, Dr. Heinzelmann-Schwarz and her colleagues said.
“In contrast to available expensive maintenance medications like antiangiogenic [drugs] and PARP inhibitors, antihormonal drugs have a favorable safety profile, low cost, easy intake regimen with one tablet daily and an established prognostic target,” they added.
While the role of aromatase inhibitor maintenance therapy in high-grade serous ovarian cancer is unclear, previous studies have shown that patients with low-grade serous ovarian cancer may benefit from endocrine therapy.
Those studies in low-grade serous ovarian cancer include several small case series, and one retrospective analysis showing improved progression-free survival among women treated with endocrine therapy versus women who received observation only (J Clin Oncol. 2017 Apr. doi: 10.1200/JCO.2016.71.0632).
The more recent report by Dr. Heinzelmann-Schwarz and her colleagues included 50 women with ER-positive, FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stage III/IV high-grade serous ovarian cancer who were offered off-label letrozole treatment after debulking surgery and platinum-based chemotherapy. Twenty-three received letrozole maintenance treatment, and 27 declined.
In the group of women who received letrozole maintenance treatment, 60% were recurrence free at 24 months, compared with 38.5% of patients in the observation group (P = .035).
“This positive effect could particularly be seen when the treatment was initiated within 3 months after the end of adjuvant chemotherapy,” Dr. Heinzelmann-Schwarz and her coauthors wrote.
Among women with residual disease who received maintenance bevacizumab in addition to letrozole, 87.5% were recurrence free at 12 months, compared with 20.8% of patients who received bevacizumab only, the investigators said.
Minor side effects such as hot flushes, fatigue, and bone pain led to discontinuation in two patients (6.4%), and no serious adverse effects were seen during treatment, according to investigators.
Almost half of all high-grade serous ovarian cancers express ER, according to results of separate retrospective analyses also described by Dr. Heinzelmann-Schwarz and her colleagues in Gynecologic Oncology. They found that ER expression was similar regardless of drug resistance status (platinum sensitive versus platinum resistant) or treatment setting (primary or recurrent).
Dr. Heinzelmann-Schwarz and colleagues declared no conflicts of interest.
SOURCE: Heinzelmann-Schwarz V et al. Gyn Oncol. 2018 Jan. doi: 10.1016/j.ygyno.2017.10.036.
Maintenance therapy with an aromatase inhibitor may improve progression-free survival in women with estrogen receptor (ER)–positive, high-grade serous ovarian cancers, results of a non-randomized, single-center study suggest.
Patients who received compared with patients who declined the treatment, investigators reported in Gynecologic Oncology.
The benefit of letrozole maintenance treatment was also apparent in women with residual disease who received bevacizumab maintenance treatment, wrote first author Viola Heinzelmann-Schwarz, MD, of the Gynecological Cancer Center, University of Basel, Switzerland, and her coauthors.
The results “strongly suggest that endocrine maintenance therapy has more advantage than disadvantage for use in ovarian cancer patients and seems clearly justified,” when considered alongside other data regarding the potential benefit of letrozole in other treatment settings, Dr. Heinzelmann-Schwarz and her colleagues said.
“In contrast to available expensive maintenance medications like antiangiogenic [drugs] and PARP inhibitors, antihormonal drugs have a favorable safety profile, low cost, easy intake regimen with one tablet daily and an established prognostic target,” they added.
While the role of aromatase inhibitor maintenance therapy in high-grade serous ovarian cancer is unclear, previous studies have shown that patients with low-grade serous ovarian cancer may benefit from endocrine therapy.
Those studies in low-grade serous ovarian cancer include several small case series, and one retrospective analysis showing improved progression-free survival among women treated with endocrine therapy versus women who received observation only (J Clin Oncol. 2017 Apr. doi: 10.1200/JCO.2016.71.0632).
The more recent report by Dr. Heinzelmann-Schwarz and her colleagues included 50 women with ER-positive, FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stage III/IV high-grade serous ovarian cancer who were offered off-label letrozole treatment after debulking surgery and platinum-based chemotherapy. Twenty-three received letrozole maintenance treatment, and 27 declined.
In the group of women who received letrozole maintenance treatment, 60% were recurrence free at 24 months, compared with 38.5% of patients in the observation group (P = .035).
“This positive effect could particularly be seen when the treatment was initiated within 3 months after the end of adjuvant chemotherapy,” Dr. Heinzelmann-Schwarz and her coauthors wrote.
Among women with residual disease who received maintenance bevacizumab in addition to letrozole, 87.5% were recurrence free at 12 months, compared with 20.8% of patients who received bevacizumab only, the investigators said.
Minor side effects such as hot flushes, fatigue, and bone pain led to discontinuation in two patients (6.4%), and no serious adverse effects were seen during treatment, according to investigators.
Almost half of all high-grade serous ovarian cancers express ER, according to results of separate retrospective analyses also described by Dr. Heinzelmann-Schwarz and her colleagues in Gynecologic Oncology. They found that ER expression was similar regardless of drug resistance status (platinum sensitive versus platinum resistant) or treatment setting (primary or recurrent).
Dr. Heinzelmann-Schwarz and colleagues declared no conflicts of interest.
SOURCE: Heinzelmann-Schwarz V et al. Gyn Oncol. 2018 Jan. doi: 10.1016/j.ygyno.2017.10.036.
Maintenance therapy with an aromatase inhibitor may improve progression-free survival in women with estrogen receptor (ER)–positive, high-grade serous ovarian cancers, results of a non-randomized, single-center study suggest.
Patients who received compared with patients who declined the treatment, investigators reported in Gynecologic Oncology.
The benefit of letrozole maintenance treatment was also apparent in women with residual disease who received bevacizumab maintenance treatment, wrote first author Viola Heinzelmann-Schwarz, MD, of the Gynecological Cancer Center, University of Basel, Switzerland, and her coauthors.
The results “strongly suggest that endocrine maintenance therapy has more advantage than disadvantage for use in ovarian cancer patients and seems clearly justified,” when considered alongside other data regarding the potential benefit of letrozole in other treatment settings, Dr. Heinzelmann-Schwarz and her colleagues said.
“In contrast to available expensive maintenance medications like antiangiogenic [drugs] and PARP inhibitors, antihormonal drugs have a favorable safety profile, low cost, easy intake regimen with one tablet daily and an established prognostic target,” they added.
While the role of aromatase inhibitor maintenance therapy in high-grade serous ovarian cancer is unclear, previous studies have shown that patients with low-grade serous ovarian cancer may benefit from endocrine therapy.
Those studies in low-grade serous ovarian cancer include several small case series, and one retrospective analysis showing improved progression-free survival among women treated with endocrine therapy versus women who received observation only (J Clin Oncol. 2017 Apr. doi: 10.1200/JCO.2016.71.0632).
The more recent report by Dr. Heinzelmann-Schwarz and her colleagues included 50 women with ER-positive, FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stage III/IV high-grade serous ovarian cancer who were offered off-label letrozole treatment after debulking surgery and platinum-based chemotherapy. Twenty-three received letrozole maintenance treatment, and 27 declined.
In the group of women who received letrozole maintenance treatment, 60% were recurrence free at 24 months, compared with 38.5% of patients in the observation group (P = .035).
“This positive effect could particularly be seen when the treatment was initiated within 3 months after the end of adjuvant chemotherapy,” Dr. Heinzelmann-Schwarz and her coauthors wrote.
Among women with residual disease who received maintenance bevacizumab in addition to letrozole, 87.5% were recurrence free at 12 months, compared with 20.8% of patients who received bevacizumab only, the investigators said.
Minor side effects such as hot flushes, fatigue, and bone pain led to discontinuation in two patients (6.4%), and no serious adverse effects were seen during treatment, according to investigators.
Almost half of all high-grade serous ovarian cancers express ER, according to results of separate retrospective analyses also described by Dr. Heinzelmann-Schwarz and her colleagues in Gynecologic Oncology. They found that ER expression was similar regardless of drug resistance status (platinum sensitive versus platinum resistant) or treatment setting (primary or recurrent).
Dr. Heinzelmann-Schwarz and colleagues declared no conflicts of interest.
SOURCE: Heinzelmann-Schwarz V et al. Gyn Oncol. 2018 Jan. doi: 10.1016/j.ygyno.2017.10.036.
FROM GYNECOLOGIC ONCOLOGY
Key clinical point: Endocrine therapy may have a role in maintenance treatment for patients with estrogen receptor (ER)–positive high-grade serous ovarian cancer (HGSOC) after debulking surgery and platinum-based chemotherapy.
Major finding: Recurrence-free survival at 24 months was 60% for patients receiving the aromatase inhibitor letrozole as maintenance therapy, compared with 38.5% for patients who declined treatment (P = .035).
Data source: A prospective, single-center, nonrandomized study including 50 patients with newly diagnosed FIGO stage III/IV HGSOC and positive estrogen receptor expression.
Disclosures: The authors declared no conflicts of interest.
Source: Heinzelmann-Schwarz V et al. Gyn Oncol. 2018 Jan. doi: 10.1016/j.ygyno.2017.10.036.
Frontline brentuximab vedotin improved Hodgkin lymphoma outcomes
Replacing bleomycin with brentuximab vedotin in the classic ABVD regimen improved a measure of progression-free survival and reduced pulmonary toxicity in patients with previously untreated Hodgkin lymphoma, findings from a randomized, phase 3 trial suggest.
Patients receiving brentuximab plus chemotherapy had a “statistically significant and clinically meaningful improvement” in the rate of modified progression-free survival, according to results published in the New England Journal of Medicine.
Pulmonary toxicity also occurred at a lower rate with the regimen containing brentuximab, an anti-CD30 antibody–drug conjugate, wrote Joseph M. Connors, MD, of the British Columbia Cancer Agency, Vancouver, and his coauthors.
Taken together, these findings suggest brentuximab vedotin and chemotherapy had “substantially less pulmonary toxicity and appears to be more effective for frontline treatment of advanced-stage classic Hodgkin lymphoma,” the researchers wrote.
Bleomycin is often omitted from later cycles of chemotherapy for patients with Hodgkin lymphoma due to pulmonary symptoms, and is sometimes associated with unpredictable or even fatal pulmonary toxicity, the researchers noted.
The brentuximab vedotin arm of the trial did have more neurotoxicity, which was largely reversible, and more myelotoxicity, though that “can be ameliorated with prophylactic granulocyte colony-stimulating factor (G-CSF),” the researchers wrote.
The study by Dr. Connors and colleagues, known as ECHELON-1, was an open-label, multicenter, randomized phase 3 trial including patients with previously untreated stage III or IV classic Hodgkin lymphoma. Among enrolled patients, 664 received brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD), and 670 received standard doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).
The study used a primary endpoint of progression-free survival augmented to include not only time to disease progression or death, but also “modified progression,” which the researchers defined as evidence of noncomplete response at the end of frontline chemotherapy.
It is accepted practice to give more chemotherapy or radiotherapy in Hodgkin lymphoma patients who have a positive PET scan at the end of frontline therapy, since metabolically detectable residual disease reliably predicts imminent progression, Dr. Connors and coauthors wrote.
“In this context, the conventional endpoint of progression-free survival does not accurately assess the curative intent of frontline chemotherapy,” they wrote.
With a median 24.9-month follow-up, modified 2-year progression-free survival in the trial was 82.1% for patients receiving brentuximab plus AVD, versus 77.2% for ABVD (P = .03), a 23% risk reduction.
Pulmonary toxicity of grade 3 or higher occurred in less than 1% of patients in the brentuximab vedotin plus AVD arm of the trial and in 3% of the ABVD arm.
Neutropenia was reported in 58% and 45% in the brentuximab vedotin plus AVD and ABVD arms, respectively, while febrile neutropenia was reported in 19% and 8%, respectively.
In the brentuximab plus AVD group, the rate of febrile neutropenia was 11% for those patients who received primary prophylaxis with G-CSF, and 21% for patients who did not, the researchers noted.
Peripheral neuropathy was seen in 67% and 43% of the brentuximab vedotin plus AVD and ABVD arms, respectively, and about two-thirds of the patients in the brentuximab vedotin plus AVD arm had improvement or resolution at the final follow-up visit.
The study was supported by Millennium Pharmaceuticals and Seattle Genetics. Researchers reported ties to Millennium Pharmaceuticals, Takeda Pharmaceuticals, Seattle Genetics, and other companies.
SOURCE: Connors JM et al. N Engl J Med. 2018;378:331-44.
The incorporation of the CD30 immunotoxin brentuximab vedotin into frontline therapy for Hodgkin lymphoma “has been eagerly anticipated, and the wait is over,” Dan L. Longo, MD, and Vincent T. DeVita Jr., MD, wrote in an editorial.
Results of the randomized phase 3 trial by Dr. Connors and colleagues suggest that, with a relatively short follow-up, adding brentuximab vedotin to AVD combination chemotherapy “merits consideration” as a first-line treatment, according to Dr. Longo and Dr. DeVita.
“Although it is too early to rule out unanticipated late side effects … brentuximab vedotin + AVD appears to be more effective than ABVD (and is unlikely to be less effective) and is associated with fewer, more treatable toxicities,” they wrote.
Adverse effects of ABVD are generally modest, but the bleomycin in the regimen can result in serious pulmonary toxicity. While the rate of serious pulmonary toxicity is low, “clinicians have the impression that it is unpredictable,” the authors noted.
Beyond a significant improvement in modified progression-free survival with a follow-up of 25 months, brentuximab vedotin plus AVD was associated with lower pulmonary toxicity, they noted.
While the brentuximab vedotin had more neutropenia and neuropathy, neutropenia could be addressed with G-CSF between doses, and neuropathy was mainly low grade and completely resolved most of the time, the authors said.
Brentuximab had promising single-agent activity in previous Hodgkin lymphoma studies, so substituting it for bleomycin “had the potential to improve on ABVD. And it did,” Dr. Longo and Dr. DeVita wrote.
Dr. Longo is with Dana-Farber Cancer Institute, Boston, and Dr. DeVita is with the Yale Cancer Center, New Haven, Conn. These comments are based on their editorial appearing in the New England Journal of Medicine (2018 Jan 24. doi: 10.1056/NEJMe1715141). Dr. DeVita reported no disclosures, and Dr. Longo reported employment as Deputy Editor with the New England Journal of Medicine.
The incorporation of the CD30 immunotoxin brentuximab vedotin into frontline therapy for Hodgkin lymphoma “has been eagerly anticipated, and the wait is over,” Dan L. Longo, MD, and Vincent T. DeVita Jr., MD, wrote in an editorial.
Results of the randomized phase 3 trial by Dr. Connors and colleagues suggest that, with a relatively short follow-up, adding brentuximab vedotin to AVD combination chemotherapy “merits consideration” as a first-line treatment, according to Dr. Longo and Dr. DeVita.
“Although it is too early to rule out unanticipated late side effects … brentuximab vedotin + AVD appears to be more effective than ABVD (and is unlikely to be less effective) and is associated with fewer, more treatable toxicities,” they wrote.
Adverse effects of ABVD are generally modest, but the bleomycin in the regimen can result in serious pulmonary toxicity. While the rate of serious pulmonary toxicity is low, “clinicians have the impression that it is unpredictable,” the authors noted.
Beyond a significant improvement in modified progression-free survival with a follow-up of 25 months, brentuximab vedotin plus AVD was associated with lower pulmonary toxicity, they noted.
While the brentuximab vedotin had more neutropenia and neuropathy, neutropenia could be addressed with G-CSF between doses, and neuropathy was mainly low grade and completely resolved most of the time, the authors said.
Brentuximab had promising single-agent activity in previous Hodgkin lymphoma studies, so substituting it for bleomycin “had the potential to improve on ABVD. And it did,” Dr. Longo and Dr. DeVita wrote.
Dr. Longo is with Dana-Farber Cancer Institute, Boston, and Dr. DeVita is with the Yale Cancer Center, New Haven, Conn. These comments are based on their editorial appearing in the New England Journal of Medicine (2018 Jan 24. doi: 10.1056/NEJMe1715141). Dr. DeVita reported no disclosures, and Dr. Longo reported employment as Deputy Editor with the New England Journal of Medicine.
The incorporation of the CD30 immunotoxin brentuximab vedotin into frontline therapy for Hodgkin lymphoma “has been eagerly anticipated, and the wait is over,” Dan L. Longo, MD, and Vincent T. DeVita Jr., MD, wrote in an editorial.
Results of the randomized phase 3 trial by Dr. Connors and colleagues suggest that, with a relatively short follow-up, adding brentuximab vedotin to AVD combination chemotherapy “merits consideration” as a first-line treatment, according to Dr. Longo and Dr. DeVita.
“Although it is too early to rule out unanticipated late side effects … brentuximab vedotin + AVD appears to be more effective than ABVD (and is unlikely to be less effective) and is associated with fewer, more treatable toxicities,” they wrote.
Adverse effects of ABVD are generally modest, but the bleomycin in the regimen can result in serious pulmonary toxicity. While the rate of serious pulmonary toxicity is low, “clinicians have the impression that it is unpredictable,” the authors noted.
Beyond a significant improvement in modified progression-free survival with a follow-up of 25 months, brentuximab vedotin plus AVD was associated with lower pulmonary toxicity, they noted.
While the brentuximab vedotin had more neutropenia and neuropathy, neutropenia could be addressed with G-CSF between doses, and neuropathy was mainly low grade and completely resolved most of the time, the authors said.
Brentuximab had promising single-agent activity in previous Hodgkin lymphoma studies, so substituting it for bleomycin “had the potential to improve on ABVD. And it did,” Dr. Longo and Dr. DeVita wrote.
Dr. Longo is with Dana-Farber Cancer Institute, Boston, and Dr. DeVita is with the Yale Cancer Center, New Haven, Conn. These comments are based on their editorial appearing in the New England Journal of Medicine (2018 Jan 24. doi: 10.1056/NEJMe1715141). Dr. DeVita reported no disclosures, and Dr. Longo reported employment as Deputy Editor with the New England Journal of Medicine.
Replacing bleomycin with brentuximab vedotin in the classic ABVD regimen improved a measure of progression-free survival and reduced pulmonary toxicity in patients with previously untreated Hodgkin lymphoma, findings from a randomized, phase 3 trial suggest.
Patients receiving brentuximab plus chemotherapy had a “statistically significant and clinically meaningful improvement” in the rate of modified progression-free survival, according to results published in the New England Journal of Medicine.
Pulmonary toxicity also occurred at a lower rate with the regimen containing brentuximab, an anti-CD30 antibody–drug conjugate, wrote Joseph M. Connors, MD, of the British Columbia Cancer Agency, Vancouver, and his coauthors.
Taken together, these findings suggest brentuximab vedotin and chemotherapy had “substantially less pulmonary toxicity and appears to be more effective for frontline treatment of advanced-stage classic Hodgkin lymphoma,” the researchers wrote.
Bleomycin is often omitted from later cycles of chemotherapy for patients with Hodgkin lymphoma due to pulmonary symptoms, and is sometimes associated with unpredictable or even fatal pulmonary toxicity, the researchers noted.
The brentuximab vedotin arm of the trial did have more neurotoxicity, which was largely reversible, and more myelotoxicity, though that “can be ameliorated with prophylactic granulocyte colony-stimulating factor (G-CSF),” the researchers wrote.
The study by Dr. Connors and colleagues, known as ECHELON-1, was an open-label, multicenter, randomized phase 3 trial including patients with previously untreated stage III or IV classic Hodgkin lymphoma. Among enrolled patients, 664 received brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD), and 670 received standard doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).
The study used a primary endpoint of progression-free survival augmented to include not only time to disease progression or death, but also “modified progression,” which the researchers defined as evidence of noncomplete response at the end of frontline chemotherapy.
It is accepted practice to give more chemotherapy or radiotherapy in Hodgkin lymphoma patients who have a positive PET scan at the end of frontline therapy, since metabolically detectable residual disease reliably predicts imminent progression, Dr. Connors and coauthors wrote.
“In this context, the conventional endpoint of progression-free survival does not accurately assess the curative intent of frontline chemotherapy,” they wrote.
With a median 24.9-month follow-up, modified 2-year progression-free survival in the trial was 82.1% for patients receiving brentuximab plus AVD, versus 77.2% for ABVD (P = .03), a 23% risk reduction.
Pulmonary toxicity of grade 3 or higher occurred in less than 1% of patients in the brentuximab vedotin plus AVD arm of the trial and in 3% of the ABVD arm.
Neutropenia was reported in 58% and 45% in the brentuximab vedotin plus AVD and ABVD arms, respectively, while febrile neutropenia was reported in 19% and 8%, respectively.
In the brentuximab plus AVD group, the rate of febrile neutropenia was 11% for those patients who received primary prophylaxis with G-CSF, and 21% for patients who did not, the researchers noted.
Peripheral neuropathy was seen in 67% and 43% of the brentuximab vedotin plus AVD and ABVD arms, respectively, and about two-thirds of the patients in the brentuximab vedotin plus AVD arm had improvement or resolution at the final follow-up visit.
The study was supported by Millennium Pharmaceuticals and Seattle Genetics. Researchers reported ties to Millennium Pharmaceuticals, Takeda Pharmaceuticals, Seattle Genetics, and other companies.
SOURCE: Connors JM et al. N Engl J Med. 2018;378:331-44.
Replacing bleomycin with brentuximab vedotin in the classic ABVD regimen improved a measure of progression-free survival and reduced pulmonary toxicity in patients with previously untreated Hodgkin lymphoma, findings from a randomized, phase 3 trial suggest.
Patients receiving brentuximab plus chemotherapy had a “statistically significant and clinically meaningful improvement” in the rate of modified progression-free survival, according to results published in the New England Journal of Medicine.
Pulmonary toxicity also occurred at a lower rate with the regimen containing brentuximab, an anti-CD30 antibody–drug conjugate, wrote Joseph M. Connors, MD, of the British Columbia Cancer Agency, Vancouver, and his coauthors.
Taken together, these findings suggest brentuximab vedotin and chemotherapy had “substantially less pulmonary toxicity and appears to be more effective for frontline treatment of advanced-stage classic Hodgkin lymphoma,” the researchers wrote.
Bleomycin is often omitted from later cycles of chemotherapy for patients with Hodgkin lymphoma due to pulmonary symptoms, and is sometimes associated with unpredictable or even fatal pulmonary toxicity, the researchers noted.
The brentuximab vedotin arm of the trial did have more neurotoxicity, which was largely reversible, and more myelotoxicity, though that “can be ameliorated with prophylactic granulocyte colony-stimulating factor (G-CSF),” the researchers wrote.
The study by Dr. Connors and colleagues, known as ECHELON-1, was an open-label, multicenter, randomized phase 3 trial including patients with previously untreated stage III or IV classic Hodgkin lymphoma. Among enrolled patients, 664 received brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD), and 670 received standard doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).
The study used a primary endpoint of progression-free survival augmented to include not only time to disease progression or death, but also “modified progression,” which the researchers defined as evidence of noncomplete response at the end of frontline chemotherapy.
It is accepted practice to give more chemotherapy or radiotherapy in Hodgkin lymphoma patients who have a positive PET scan at the end of frontline therapy, since metabolically detectable residual disease reliably predicts imminent progression, Dr. Connors and coauthors wrote.
“In this context, the conventional endpoint of progression-free survival does not accurately assess the curative intent of frontline chemotherapy,” they wrote.
With a median 24.9-month follow-up, modified 2-year progression-free survival in the trial was 82.1% for patients receiving brentuximab plus AVD, versus 77.2% for ABVD (P = .03), a 23% risk reduction.
Pulmonary toxicity of grade 3 or higher occurred in less than 1% of patients in the brentuximab vedotin plus AVD arm of the trial and in 3% of the ABVD arm.
Neutropenia was reported in 58% and 45% in the brentuximab vedotin plus AVD and ABVD arms, respectively, while febrile neutropenia was reported in 19% and 8%, respectively.
In the brentuximab plus AVD group, the rate of febrile neutropenia was 11% for those patients who received primary prophylaxis with G-CSF, and 21% for patients who did not, the researchers noted.
Peripheral neuropathy was seen in 67% and 43% of the brentuximab vedotin plus AVD and ABVD arms, respectively, and about two-thirds of the patients in the brentuximab vedotin plus AVD arm had improvement or resolution at the final follow-up visit.
The study was supported by Millennium Pharmaceuticals and Seattle Genetics. Researchers reported ties to Millennium Pharmaceuticals, Takeda Pharmaceuticals, Seattle Genetics, and other companies.
SOURCE: Connors JM et al. N Engl J Med. 2018;378:331-44.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: Modified 2-year progression-free survival was 82.1% with the brentuximab vedotin–containing regimen versus 77.2% for ABVD (P = .03).
Study details: An open-label, multicenter, randomized phase 3 trial including 1,334 patients with previously untreated stage III or IV classic Hodgkin lymphoma.
Disclosures: The study was supported by Millennium Pharmaceuticals and Seattle Genetics. Researchers reported ties to Millennium Pharmaceuticals, Takeda Pharmaceuticals, Seattle Genetics, and other companies.
Source: Connors JM et al. N Engl J Med. 2018;378:331-44.