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ZMapp shows promise for Ebola treatment, but misses efficacy goal
ZMapp, a potential monoclonal antibody treatment for Ebola virus disease, did not meet its efficacy goal in a clinical trial of patients in Liberia, Sierra Leone, and Guinea, according to a report in the New England Journal of Medicine.
ZMapp, developed by Mapp Biopharmaceutical, comprises three different laboratory-generated monoclonal antibodies. The drug targets the main surface protein of the Ebola virus. Earlier studies in nonhuman primates demonstrated that ZMapp had strong antiviral activity and prevented death when administered as late as 5 days after experimental infection with the Zaire Ebola virus strain.
The process of ZMapp infusion was generally safe, with only one serious adverse event – hypertension – attributed to the infusion itself. Of the 93 infusions attempted in the ZMapp group, 8 were stopped because of adverse events, and 9 were slowed down to accommodate for side effects.
While ZMapp did not meet its goal, the relative risk of death was 40% lower in the ZMapp group then in the control group. Treatment with ZMapp was delayed for a week after patients became symptomatic, exceeding the 5-day window where ZMapp has been shown to have at least 90% effectiveness. In addition, of the eight patients who died in the ZMapp group, seven died before the second of the three planned ZMapp infusions were delivered.
The abrupt end to the Ebola epidemic prevented the ZMapp trial from being adequately completed. A goal of 100 patients in both groups was desired but could not be reached.
“Despite the concerted efforts of many dedicated researchers domestically and internationally who participated in this and other trials, the outbreak appears to have ended with no incontrovertible evidence that any single treatment intervention, or combination of interventions, was unequivocally superior to the types of supportive medical care typically provided,” the investigators said.
Find the full study in the New England Journal of Medicine (doi: 10.1056/NEJMoa1604330).
ZMapp, a potential monoclonal antibody treatment for Ebola virus disease, did not meet its efficacy goal in a clinical trial of patients in Liberia, Sierra Leone, and Guinea, according to a report in the New England Journal of Medicine.
ZMapp, developed by Mapp Biopharmaceutical, comprises three different laboratory-generated monoclonal antibodies. The drug targets the main surface protein of the Ebola virus. Earlier studies in nonhuman primates demonstrated that ZMapp had strong antiviral activity and prevented death when administered as late as 5 days after experimental infection with the Zaire Ebola virus strain.
The process of ZMapp infusion was generally safe, with only one serious adverse event – hypertension – attributed to the infusion itself. Of the 93 infusions attempted in the ZMapp group, 8 were stopped because of adverse events, and 9 were slowed down to accommodate for side effects.
While ZMapp did not meet its goal, the relative risk of death was 40% lower in the ZMapp group then in the control group. Treatment with ZMapp was delayed for a week after patients became symptomatic, exceeding the 5-day window where ZMapp has been shown to have at least 90% effectiveness. In addition, of the eight patients who died in the ZMapp group, seven died before the second of the three planned ZMapp infusions were delivered.
The abrupt end to the Ebola epidemic prevented the ZMapp trial from being adequately completed. A goal of 100 patients in both groups was desired but could not be reached.
“Despite the concerted efforts of many dedicated researchers domestically and internationally who participated in this and other trials, the outbreak appears to have ended with no incontrovertible evidence that any single treatment intervention, or combination of interventions, was unequivocally superior to the types of supportive medical care typically provided,” the investigators said.
Find the full study in the New England Journal of Medicine (doi: 10.1056/NEJMoa1604330).
ZMapp, a potential monoclonal antibody treatment for Ebola virus disease, did not meet its efficacy goal in a clinical trial of patients in Liberia, Sierra Leone, and Guinea, according to a report in the New England Journal of Medicine.
ZMapp, developed by Mapp Biopharmaceutical, comprises three different laboratory-generated monoclonal antibodies. The drug targets the main surface protein of the Ebola virus. Earlier studies in nonhuman primates demonstrated that ZMapp had strong antiviral activity and prevented death when administered as late as 5 days after experimental infection with the Zaire Ebola virus strain.
The process of ZMapp infusion was generally safe, with only one serious adverse event – hypertension – attributed to the infusion itself. Of the 93 infusions attempted in the ZMapp group, 8 were stopped because of adverse events, and 9 were slowed down to accommodate for side effects.
While ZMapp did not meet its goal, the relative risk of death was 40% lower in the ZMapp group then in the control group. Treatment with ZMapp was delayed for a week after patients became symptomatic, exceeding the 5-day window where ZMapp has been shown to have at least 90% effectiveness. In addition, of the eight patients who died in the ZMapp group, seven died before the second of the three planned ZMapp infusions were delivered.
The abrupt end to the Ebola epidemic prevented the ZMapp trial from being adequately completed. A goal of 100 patients in both groups was desired but could not be reached.
“Despite the concerted efforts of many dedicated researchers domestically and internationally who participated in this and other trials, the outbreak appears to have ended with no incontrovertible evidence that any single treatment intervention, or combination of interventions, was unequivocally superior to the types of supportive medical care typically provided,” the investigators said.
Find the full study in the New England Journal of Medicine (doi: 10.1056/NEJMoa1604330).
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
VIDEO: The Business of Hospital Medicine
The business of hospital medicine is an important factor in individual clinicians' careers and for the specialty as a whole. Dr. Jasen Gundersen of TeamHealth and James Levy of Indigo Health Partners talk about the importance of recognizing the personal, and the system-wide, impacts and opportunities of the business side of HM.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The business of hospital medicine is an important factor in individual clinicians' careers and for the specialty as a whole. Dr. Jasen Gundersen of TeamHealth and James Levy of Indigo Health Partners talk about the importance of recognizing the personal, and the system-wide, impacts and opportunities of the business side of HM.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The business of hospital medicine is an important factor in individual clinicians' careers and for the specialty as a whole. Dr. Jasen Gundersen of TeamHealth and James Levy of Indigo Health Partners talk about the importance of recognizing the personal, and the system-wide, impacts and opportunities of the business side of HM.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Hepatitis Outlook: August 2016
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.
A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.
Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.
Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.
A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.
Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.
Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.
A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.
Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.
A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.
From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.
Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.
An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.
A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
[email protected]
On Twitter @richpizzi
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.
A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.
Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.
Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.
A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.
Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.
Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.
A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.
Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.
A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.
From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.
Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.
An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.
A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
[email protected]
On Twitter @richpizzi
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
A study in Hepatology has provided a preclinical risk assessment paradigm with which to better understand cardiovascular drug-drug interaction risk for hepatitis C–virus infected patients treated with sofosbuvir in combination with other direct acting antivirals and the antiarrhythmic drug amiodarone.
A Japanese study found that, although levels of Wisteria floribunda agglutinin-positive Mac-2-binding protein could be a useful indicator of liver fibrosis in patients with hepatitis B or C infection, WFA+-M2BP levels in the two groups significantly differed, even in the same degree of fibrosis.
Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for hepatitis C virus–associated mixed cryoglobulinemia patients, according to a recent study.
Another recent study found that pegylated interferon (PegIFN) intensification in hepatitis B “e” antigen (HBeAg)-positive coinfected patients did not lead to increased clearance rates of HBeAg or hepatitis B surface antigen quantification (qHBsAg), despite faster declines of antigen levels while on PegIFN.
A study in HIV Medicine found that, under real-life conditions, treatment of patients infected with hepatitis C virus and of patients coinfected with HCV/HIV with all-oral direct-acting antiviral combinations led to high and similar rates of sustained virological response 12 weeks after the end of therapy.
Hepatitis B virus coinfection was the most important risk factor for liver fibrosis and cirrhosis in HIV-infected patients, and should be diagnosed early in HIV care to optimize treatment outcomes, a recent study showed.
Immunity persisted 24 months after a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine was administered to school-age children, according to a study published in Human Vaccines & Immunotherapeutics.
A hepatitis C treatment scale-up strategy in Rhode Island could reduce cirrhosis cases and liver-related deaths by 78.9% and 72.4%, respectively, by 2030, according to a study in Epidemiology and Infection.
Viral blipping is a frequent event during nucleoside analogue treatment of patients with chronic hepatitis B virus infection, a study found, although it did not lead to any clinically significant outcomes and thus may not require more frequent blood work and patient visits in clinical practice.
A study of liver and spleen stiffness in hepatitis C virus–infected patients – with advanced liver disease and sustained virologic response after interferon-free treatment – found that improvement of liver stiffness may be due to reduced necroinflammation, and to a lesser extent regression of cirrhosis. Improvement was more pronounced between therapy baseline and end of treatment than therapy baseline and 24 weeks after end of treatment.
From 2000 to 2011, 4,346 adults who died in New York City had a report of a hepatitis B virus infection (0.7%), according to a study in Epidemiology and Infection. Of the HBV-infected decedents, 1,074 (25%) were HIV coinfected. Fifty-five percent of HBV monoinfected and 95% of HBV/HIV coinfected decedents died prematurely, the researchers found.
Prison-based hepatitis C virus treatment achieves outcomes similar to those of community-based treatment, according to a study in the Journal of Viral Hepatitis, with those not released or transferred during treatment doing particularly well.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men are effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
The results of an international quality control study underline the urgent need to improve methods used to monitor hepatitis Delta virus viremia.
An investigation of a hepatitis E virus genotype 4 outbreak in Zhejiang Province, China, found that the outbreak was most likely caused by contaminated tap water rather than food.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in well-selected hepatitis C virus mono- and HIV/HCV-coinfected patients in a real-world setting.
A study of historical events fueling the cross-continental spread of hepatitis C virus epidemics said drivers for the epidemic were the advent of intravenous medical therapies and devices, growth in the heroin trade, and population mixing during armed conflicts.
AGA Resource
Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.
[email protected]
On Twitter @richpizzi
CDC: Improvement in breast cancer mortality slower among black women
Breast cancer mortality rates decreased for both white and black women from 2000 to 2014, but the decrease was slower for black women, according to a report by investigators with the Centers for Disease Control and Prevention.
The mortality rate decreased an average of 1.9% per year for white women, compared with an average decrease of 1.5% per year for black women, in an analysis of data from United States Cancer Statistics (USCS). Between 2010 and 2014, breast cancer mortality was 41% higher among black women (29.2 deaths per 100,000 people) than among white women (20.6 deaths per 100,000 population), reported Lisa C. Richardson, MD, and her associates at the CDC’s National Center for Chronic Disease Prevention and Health Promotion (MMWR. 2016 Oct 14;65[40]:1093-8).
Between 1999 and 2004, mortality rates decreased only for white woman older than 50 years.
USCS includes incidence data from the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program, and mortality data from the National Vital Statistics System.
“When combined with population-based approaches to increase knowledge of family history of cancer, increase physical activity, promote a healthy diet to maintain a healthy bodyweight, and increase screening for breast cancer, targeted treatment interventions could reduce racial disparities in breast cancer,” the investigators said. “A fuller understanding of [breast cancer’s] exact mechanisms might lead to more tailored interventions that could decrease mortality disparities.”
[email protected]
On Twitter @jessnicolecraig
Breast cancer mortality rates decreased for both white and black women from 2000 to 2014, but the decrease was slower for black women, according to a report by investigators with the Centers for Disease Control and Prevention.
The mortality rate decreased an average of 1.9% per year for white women, compared with an average decrease of 1.5% per year for black women, in an analysis of data from United States Cancer Statistics (USCS). Between 2010 and 2014, breast cancer mortality was 41% higher among black women (29.2 deaths per 100,000 people) than among white women (20.6 deaths per 100,000 population), reported Lisa C. Richardson, MD, and her associates at the CDC’s National Center for Chronic Disease Prevention and Health Promotion (MMWR. 2016 Oct 14;65[40]:1093-8).
Between 1999 and 2004, mortality rates decreased only for white woman older than 50 years.
USCS includes incidence data from the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program, and mortality data from the National Vital Statistics System.
“When combined with population-based approaches to increase knowledge of family history of cancer, increase physical activity, promote a healthy diet to maintain a healthy bodyweight, and increase screening for breast cancer, targeted treatment interventions could reduce racial disparities in breast cancer,” the investigators said. “A fuller understanding of [breast cancer’s] exact mechanisms might lead to more tailored interventions that could decrease mortality disparities.”
[email protected]
On Twitter @jessnicolecraig
Breast cancer mortality rates decreased for both white and black women from 2000 to 2014, but the decrease was slower for black women, according to a report by investigators with the Centers for Disease Control and Prevention.
The mortality rate decreased an average of 1.9% per year for white women, compared with an average decrease of 1.5% per year for black women, in an analysis of data from United States Cancer Statistics (USCS). Between 2010 and 2014, breast cancer mortality was 41% higher among black women (29.2 deaths per 100,000 people) than among white women (20.6 deaths per 100,000 population), reported Lisa C. Richardson, MD, and her associates at the CDC’s National Center for Chronic Disease Prevention and Health Promotion (MMWR. 2016 Oct 14;65[40]:1093-8).
Between 1999 and 2004, mortality rates decreased only for white woman older than 50 years.
USCS includes incidence data from the CDC’s National Program of Cancer Registries and the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program, and mortality data from the National Vital Statistics System.
“When combined with population-based approaches to increase knowledge of family history of cancer, increase physical activity, promote a healthy diet to maintain a healthy bodyweight, and increase screening for breast cancer, targeted treatment interventions could reduce racial disparities in breast cancer,” the investigators said. “A fuller understanding of [breast cancer’s] exact mechanisms might lead to more tailored interventions that could decrease mortality disparities.”
[email protected]
On Twitter @jessnicolecraig
Key clinical point:
Major finding: The mortality rate decreased an average of 1.9% per year for white women, compared with an average decrease of 1.5% per year for black women.
Data source: United States Cancer Statistics (USCS).
Disclosures: The CDC supported this study.
Laparoscopy comparable to open staging for uterine papillary serous cancer
BOSTON – Laparoscopic staging of patients with uterine papillary serous carcinoma is a safe alternative to open staging and may offer some advantages, according to findings presented at the annual Minimally Invasive Surgery Week.
“Traditionally, serous papillary cancer has been treated different than the other endometrial cancers, the reason being is that it tends to behave more like ovarian cancer,” Jeanette Voice, MD, of Richmond University Medical Center in Staten Island, N.Y., said at the meeting, which was held by the Society for Laparoendoscopic Surgeons. “Patients with serous papillary cancer tend to be older [so] these patients may benefit from a less invasive surgical approach.”
Dr. Voice and her coinvestigators conducted an 8-year retrospective study of laparoscopic and open-staged cases treated from March 2007 through May 2015. Initially, 59 patients with pathology-confirmed uterine papillary serous carcinoma were identified over that time period, and were divided into two cohorts: one receiving open surgery (37 patients) and one receiving laparoscopic surgery (22 patients).
Median age, body mass index, and prior abdominal surgery rate were not significantly different between the two cohorts.
In terms of intraoperative factors, median operative times for the open and laparoscopic cohorts were similar: 196 minutes versus 216 minutes, respectively (P = .561). Similarly, the number of pelvic lymph node dissections and rate of omentectomy were also not significantly different: 18 nodes (open) versus 16 nodes (laparoscopic) (P = .96), and 100% (open) versus 91% (laparoscopic) (P = .08).
However, laparoscopic patients had more favorable median estimated blood loss (310 mL versus 175 mL, P = .048) and shorter hospital stays (4 days versus 1 day, P less than .042).
Laparoscopic patients also achieved more robust debulking to zero centimeter residual disease, with 90.5% of patients achieving it versus 65.7% of those in the open surgery cohort, but the difference was not statistically significant (P = .1).
In terms of postoperative adjuvant therapy – brachytherapy, external beam radiation, and chemotherapy – there were no significant differences in outcomes between the two cohorts. Recurrence rates were also similar, with nine recurrences in the open cohort and eight recurrences in the laparoscopic cohort. The estimated 36-month progression-free survival rates were “almost identical,” with 55.3% in the open cohort versus 53.3% in the laparoscopic (P = .727), according to Dr. Voice.
Postoperative complications were more common in the open surgery cohort (29.7%), compared with 13.6% in the laparoscopic cohort, but no statistically significant difference was found between them (P = .16).
Dr. Voice did not report information on financial disclosures.
BOSTON – Laparoscopic staging of patients with uterine papillary serous carcinoma is a safe alternative to open staging and may offer some advantages, according to findings presented at the annual Minimally Invasive Surgery Week.
“Traditionally, serous papillary cancer has been treated different than the other endometrial cancers, the reason being is that it tends to behave more like ovarian cancer,” Jeanette Voice, MD, of Richmond University Medical Center in Staten Island, N.Y., said at the meeting, which was held by the Society for Laparoendoscopic Surgeons. “Patients with serous papillary cancer tend to be older [so] these patients may benefit from a less invasive surgical approach.”
Dr. Voice and her coinvestigators conducted an 8-year retrospective study of laparoscopic and open-staged cases treated from March 2007 through May 2015. Initially, 59 patients with pathology-confirmed uterine papillary serous carcinoma were identified over that time period, and were divided into two cohorts: one receiving open surgery (37 patients) and one receiving laparoscopic surgery (22 patients).
Median age, body mass index, and prior abdominal surgery rate were not significantly different between the two cohorts.
In terms of intraoperative factors, median operative times for the open and laparoscopic cohorts were similar: 196 minutes versus 216 minutes, respectively (P = .561). Similarly, the number of pelvic lymph node dissections and rate of omentectomy were also not significantly different: 18 nodes (open) versus 16 nodes (laparoscopic) (P = .96), and 100% (open) versus 91% (laparoscopic) (P = .08).
However, laparoscopic patients had more favorable median estimated blood loss (310 mL versus 175 mL, P = .048) and shorter hospital stays (4 days versus 1 day, P less than .042).
Laparoscopic patients also achieved more robust debulking to zero centimeter residual disease, with 90.5% of patients achieving it versus 65.7% of those in the open surgery cohort, but the difference was not statistically significant (P = .1).
In terms of postoperative adjuvant therapy – brachytherapy, external beam radiation, and chemotherapy – there were no significant differences in outcomes between the two cohorts. Recurrence rates were also similar, with nine recurrences in the open cohort and eight recurrences in the laparoscopic cohort. The estimated 36-month progression-free survival rates were “almost identical,” with 55.3% in the open cohort versus 53.3% in the laparoscopic (P = .727), according to Dr. Voice.
Postoperative complications were more common in the open surgery cohort (29.7%), compared with 13.6% in the laparoscopic cohort, but no statistically significant difference was found between them (P = .16).
Dr. Voice did not report information on financial disclosures.
BOSTON – Laparoscopic staging of patients with uterine papillary serous carcinoma is a safe alternative to open staging and may offer some advantages, according to findings presented at the annual Minimally Invasive Surgery Week.
“Traditionally, serous papillary cancer has been treated different than the other endometrial cancers, the reason being is that it tends to behave more like ovarian cancer,” Jeanette Voice, MD, of Richmond University Medical Center in Staten Island, N.Y., said at the meeting, which was held by the Society for Laparoendoscopic Surgeons. “Patients with serous papillary cancer tend to be older [so] these patients may benefit from a less invasive surgical approach.”
Dr. Voice and her coinvestigators conducted an 8-year retrospective study of laparoscopic and open-staged cases treated from March 2007 through May 2015. Initially, 59 patients with pathology-confirmed uterine papillary serous carcinoma were identified over that time period, and were divided into two cohorts: one receiving open surgery (37 patients) and one receiving laparoscopic surgery (22 patients).
Median age, body mass index, and prior abdominal surgery rate were not significantly different between the two cohorts.
In terms of intraoperative factors, median operative times for the open and laparoscopic cohorts were similar: 196 minutes versus 216 minutes, respectively (P = .561). Similarly, the number of pelvic lymph node dissections and rate of omentectomy were also not significantly different: 18 nodes (open) versus 16 nodes (laparoscopic) (P = .96), and 100% (open) versus 91% (laparoscopic) (P = .08).
However, laparoscopic patients had more favorable median estimated blood loss (310 mL versus 175 mL, P = .048) and shorter hospital stays (4 days versus 1 day, P less than .042).
Laparoscopic patients also achieved more robust debulking to zero centimeter residual disease, with 90.5% of patients achieving it versus 65.7% of those in the open surgery cohort, but the difference was not statistically significant (P = .1).
In terms of postoperative adjuvant therapy – brachytherapy, external beam radiation, and chemotherapy – there were no significant differences in outcomes between the two cohorts. Recurrence rates were also similar, with nine recurrences in the open cohort and eight recurrences in the laparoscopic cohort. The estimated 36-month progression-free survival rates were “almost identical,” with 55.3% in the open cohort versus 53.3% in the laparoscopic (P = .727), according to Dr. Voice.
Postoperative complications were more common in the open surgery cohort (29.7%), compared with 13.6% in the laparoscopic cohort, but no statistically significant difference was found between them (P = .16).
Dr. Voice did not report information on financial disclosures.
AT MINIMALLY INVASIVE SURGERY WEEK
Key clinical point:
Major finding: Laparoscopic patients had lower median estimated blood loss (310 mL v. 175 mL, P = .048) and shorter hospital stays (4 days v. 1 day, P less than .042).
Data source: Retrospective review of data on 59 open and laparoscopic patients over 8 years.
Disclosures: Dr. Voice did not report information on financial disclosures.
PD-L1 positivity correlated with pembrolizumab response in advanced melanoma
Programmed death ligand–1 expression correlated positively and significantly with pembrolizumab response in advanced melanoma, based on an analysis of 405 patients from the international, multicohort, open-label phase I KEYNOTE-001 trial.
Among patients for whom 33%-65% of tumor cells expressed PD-L1, the objective rate of response was 57%, but the rate was only 8% among patients whose specimens did not express PD-L1, Adil Daud, MD, of the University of California, San Francisco, and associates reported. Taken together, the findings suggest that melanoma is most likely to respond to pembrolizumab when specimens show at least 10% positivity, the investigators reported (J Clin Oncol. 2016 Oct 10. doi: 10.1200/JCO.2016.67.2477).
Among the 405 patients who also were evaluable for tumor response, the overall objective response rate was 33% (95% confidence interval, 28%-37%). Grouping patients based on the melanoma scoring system for PD-L1 expression showed that PD-L1 positivity correlated significantly with the objective response rate (P less than .001). Furthermore, a higher PD-L1 melanoma score correlated significantly with both progression-free survival (hazard ratio, 0.76; 95% CI, 0.7-0.82) and overall survival (HR, 0.76; 95% CI, 0.69-0.83), with P values less than .001 for each association.
Median progression-free survival was 5.6 months in PD-L1–positive patients and 2.8 months in PD-L1–negative patients, while median overall survival was 30 months in PD-L1–positive patients and 12.6 months in PD-L1–negative patients, the researchers reported. “The high prevalence of PD-L1 positivity observed in this study, along with the durable responses observed in PD-L1–negative tumors, suggest that pembrolizumab treatment should not be limited to patients with PD-L1–positive tumors,” they concluded. “Ongoing clinical trials with correlative studies will further delineate the role of PD-L1 expression in melanoma.”
Merck sponsored the trial. Dr. Daud disclosed ties to Merck, OncoSec, Novartis, Genentech, Bristol-Myers Squibb, and Array BioPharma.
Programmed death ligand–1 expression correlated positively and significantly with pembrolizumab response in advanced melanoma, based on an analysis of 405 patients from the international, multicohort, open-label phase I KEYNOTE-001 trial.
Among patients for whom 33%-65% of tumor cells expressed PD-L1, the objective rate of response was 57%, but the rate was only 8% among patients whose specimens did not express PD-L1, Adil Daud, MD, of the University of California, San Francisco, and associates reported. Taken together, the findings suggest that melanoma is most likely to respond to pembrolizumab when specimens show at least 10% positivity, the investigators reported (J Clin Oncol. 2016 Oct 10. doi: 10.1200/JCO.2016.67.2477).
Among the 405 patients who also were evaluable for tumor response, the overall objective response rate was 33% (95% confidence interval, 28%-37%). Grouping patients based on the melanoma scoring system for PD-L1 expression showed that PD-L1 positivity correlated significantly with the objective response rate (P less than .001). Furthermore, a higher PD-L1 melanoma score correlated significantly with both progression-free survival (hazard ratio, 0.76; 95% CI, 0.7-0.82) and overall survival (HR, 0.76; 95% CI, 0.69-0.83), with P values less than .001 for each association.
Median progression-free survival was 5.6 months in PD-L1–positive patients and 2.8 months in PD-L1–negative patients, while median overall survival was 30 months in PD-L1–positive patients and 12.6 months in PD-L1–negative patients, the researchers reported. “The high prevalence of PD-L1 positivity observed in this study, along with the durable responses observed in PD-L1–negative tumors, suggest that pembrolizumab treatment should not be limited to patients with PD-L1–positive tumors,” they concluded. “Ongoing clinical trials with correlative studies will further delineate the role of PD-L1 expression in melanoma.”
Merck sponsored the trial. Dr. Daud disclosed ties to Merck, OncoSec, Novartis, Genentech, Bristol-Myers Squibb, and Array BioPharma.
Programmed death ligand–1 expression correlated positively and significantly with pembrolizumab response in advanced melanoma, based on an analysis of 405 patients from the international, multicohort, open-label phase I KEYNOTE-001 trial.
Among patients for whom 33%-65% of tumor cells expressed PD-L1, the objective rate of response was 57%, but the rate was only 8% among patients whose specimens did not express PD-L1, Adil Daud, MD, of the University of California, San Francisco, and associates reported. Taken together, the findings suggest that melanoma is most likely to respond to pembrolizumab when specimens show at least 10% positivity, the investigators reported (J Clin Oncol. 2016 Oct 10. doi: 10.1200/JCO.2016.67.2477).
Among the 405 patients who also were evaluable for tumor response, the overall objective response rate was 33% (95% confidence interval, 28%-37%). Grouping patients based on the melanoma scoring system for PD-L1 expression showed that PD-L1 positivity correlated significantly with the objective response rate (P less than .001). Furthermore, a higher PD-L1 melanoma score correlated significantly with both progression-free survival (hazard ratio, 0.76; 95% CI, 0.7-0.82) and overall survival (HR, 0.76; 95% CI, 0.69-0.83), with P values less than .001 for each association.
Median progression-free survival was 5.6 months in PD-L1–positive patients and 2.8 months in PD-L1–negative patients, while median overall survival was 30 months in PD-L1–positive patients and 12.6 months in PD-L1–negative patients, the researchers reported. “The high prevalence of PD-L1 positivity observed in this study, along with the durable responses observed in PD-L1–negative tumors, suggest that pembrolizumab treatment should not be limited to patients with PD-L1–positive tumors,” they concluded. “Ongoing clinical trials with correlative studies will further delineate the role of PD-L1 expression in melanoma.”
Merck sponsored the trial. Dr. Daud disclosed ties to Merck, OncoSec, Novartis, Genentech, Bristol-Myers Squibb, and Array BioPharma.
Key clinical point: PD-L1 expression correlates with pembrolizumab response in advanced melanoma.
Major finding: Higher levels of PD-L1 staining correlated positively with tumor response (P less than .001).
Data source: Analyses of 405 patients from KEYNOTE-001, an international, multicohort, open-label phase I trial of pembrolizumab in advanced melanoma.
Disclosures: Merck sponsored the trial. Dr. Daud disclosed ties to Merck, OncoSec, Novartis, Genentech, Bristol-Myers Squibb, and Array BioPharma.
Registry helps track pelvic organ prolapse outcomes in the U.S.
DENVER – Catherine Bradley, MD, said during a presentation at Pelvic Floor Disorders Week, sponsored by the American Urogynecologic Society.
“This is a unique collaborative registry created in response to U.S. industry requirements. There are many benefits to using this approach, but also many challenges. It’s a work in progress,” said Dr. Bradley, of the University of Iowa, Iowa City. She chairs the American Urogynecologic Society Research Council, which helps oversee the registry.
The purpose of the PFDR is to fulfill requirements from the Food and Drug Administration for postmarketing studies of the vaginal mesh procedure, to give surgeons a pelvic organ prolapse treatment database to track individual and aggregate outcomes for research and quality improvement purposes, and to create a framework for future clinical studies, according to Dr. Bradley.
As such, the PFDR comprises two interrelated registries, Dr. Bradley noted. The PFDR-I includes industry-sponsored studies, while the PFDR-R is the independent research registry of the American Urogynecologic Society. The PFDR previously included a third quality improvement registry, which in January 2016 was moved to a separate platform called AQUIRE.
The PFDR-I is tracking 1,620 patients who underwent 1,386 procedures for pelvic organ prolapse as part of four studies sponsored by three manufacturers, according to Dr. Bradley. The PFDR-R, for its part, has eight active sites and has enrolled 179 patients with pelvic organ prolapse, 154 of whom underwent mesh surgery and 25 of whom received vaginal pessaries, she said.
The PFDR-R is voluntary and has faced some barriers in the 10 months since its launch, Dr. Bradley said. Participation increases workload for physicians as well as data entry personnel, and patients must provide informed consent to be entered into the registry. But the benefits of participating are also substantial, she emphasized. The PFDR-R will enable surgeons to track their own outcomes in terms of caseload, anatomic outcomes, symptoms and quality of life, and adverse events. They can download their own data, compare their outcomes to others as part of highly granular benchmarking initiatives, and propose and conduct studies of the entire registry.
The PFDR is supported by ACell, ASTORA Women’s Health, Boston Scientific, and Coloplast. Dr. Bradley reported having no conflicts of interest.
DENVER – Catherine Bradley, MD, said during a presentation at Pelvic Floor Disorders Week, sponsored by the American Urogynecologic Society.
“This is a unique collaborative registry created in response to U.S. industry requirements. There are many benefits to using this approach, but also many challenges. It’s a work in progress,” said Dr. Bradley, of the University of Iowa, Iowa City. She chairs the American Urogynecologic Society Research Council, which helps oversee the registry.
The purpose of the PFDR is to fulfill requirements from the Food and Drug Administration for postmarketing studies of the vaginal mesh procedure, to give surgeons a pelvic organ prolapse treatment database to track individual and aggregate outcomes for research and quality improvement purposes, and to create a framework for future clinical studies, according to Dr. Bradley.
As such, the PFDR comprises two interrelated registries, Dr. Bradley noted. The PFDR-I includes industry-sponsored studies, while the PFDR-R is the independent research registry of the American Urogynecologic Society. The PFDR previously included a third quality improvement registry, which in January 2016 was moved to a separate platform called AQUIRE.
The PFDR-I is tracking 1,620 patients who underwent 1,386 procedures for pelvic organ prolapse as part of four studies sponsored by three manufacturers, according to Dr. Bradley. The PFDR-R, for its part, has eight active sites and has enrolled 179 patients with pelvic organ prolapse, 154 of whom underwent mesh surgery and 25 of whom received vaginal pessaries, she said.
The PFDR-R is voluntary and has faced some barriers in the 10 months since its launch, Dr. Bradley said. Participation increases workload for physicians as well as data entry personnel, and patients must provide informed consent to be entered into the registry. But the benefits of participating are also substantial, she emphasized. The PFDR-R will enable surgeons to track their own outcomes in terms of caseload, anatomic outcomes, symptoms and quality of life, and adverse events. They can download their own data, compare their outcomes to others as part of highly granular benchmarking initiatives, and propose and conduct studies of the entire registry.
The PFDR is supported by ACell, ASTORA Women’s Health, Boston Scientific, and Coloplast. Dr. Bradley reported having no conflicts of interest.
DENVER – Catherine Bradley, MD, said during a presentation at Pelvic Floor Disorders Week, sponsored by the American Urogynecologic Society.
“This is a unique collaborative registry created in response to U.S. industry requirements. There are many benefits to using this approach, but also many challenges. It’s a work in progress,” said Dr. Bradley, of the University of Iowa, Iowa City. She chairs the American Urogynecologic Society Research Council, which helps oversee the registry.
The purpose of the PFDR is to fulfill requirements from the Food and Drug Administration for postmarketing studies of the vaginal mesh procedure, to give surgeons a pelvic organ prolapse treatment database to track individual and aggregate outcomes for research and quality improvement purposes, and to create a framework for future clinical studies, according to Dr. Bradley.
As such, the PFDR comprises two interrelated registries, Dr. Bradley noted. The PFDR-I includes industry-sponsored studies, while the PFDR-R is the independent research registry of the American Urogynecologic Society. The PFDR previously included a third quality improvement registry, which in January 2016 was moved to a separate platform called AQUIRE.
The PFDR-I is tracking 1,620 patients who underwent 1,386 procedures for pelvic organ prolapse as part of four studies sponsored by three manufacturers, according to Dr. Bradley. The PFDR-R, for its part, has eight active sites and has enrolled 179 patients with pelvic organ prolapse, 154 of whom underwent mesh surgery and 25 of whom received vaginal pessaries, she said.
The PFDR-R is voluntary and has faced some barriers in the 10 months since its launch, Dr. Bradley said. Participation increases workload for physicians as well as data entry personnel, and patients must provide informed consent to be entered into the registry. But the benefits of participating are also substantial, she emphasized. The PFDR-R will enable surgeons to track their own outcomes in terms of caseload, anatomic outcomes, symptoms and quality of life, and adverse events. They can download their own data, compare their outcomes to others as part of highly granular benchmarking initiatives, and propose and conduct studies of the entire registry.
The PFDR is supported by ACell, ASTORA Women’s Health, Boston Scientific, and Coloplast. Dr. Bradley reported having no conflicts of interest.
AT PFD WEEK 2016
Pembrolizumab boosts response but not survival in small study of advanced NSCLC
COPENHAGEN – Adding the PD-1 checkpoint inhibitor pembrolizumab (Keytruda) to a standard platinum-doublet chemotherapy regimen nearly doubled response rates among patients with previously untreated advanced nonsquamous non–small cell lung cancer, but did not result in an overall survival advantage, results of a phase II trial show.
After a median follow-up of 10.6 months, the objective response rate among patients randomized to receive carboplatin and pemetrexed plus pembrolizumab was 55%, compared with 29% for patients treated with the platinum doublet alone, reported Corey J. Langer, MD, from the Abramson Cancer Center of the University of Pennsylvania, Philadelphia.
Dr. Langer presented results on one cohort in the KEYNOTE 021 trial, a phase II, randomized, open-label multicohort study looking at pembrolizumab in combination with chemotherapy or immunotherapy.
In this cohort, 123 patients with untreated stage IIIB or IV nonsquamous non–small cell lung cancer with no activating EGFR mutations or ALK translocations were randomly assigned to receive either pembrolizumab 200 mg every 3 weeks for 2 years plus carboplatin dosed to the area under the curve and infused at 5 mg/mL per min plus pemetrexed 500 mg/m2 every 3 weeks for four cycles, or to chemotherapy alone.
Following completion of the trial, patients randomized to chemotherapy could be switched over to pembrolizumab at the same dose and scheduled for up to 2 years.
As noted, for the primary endpoint of confirmed objective response rates, the rate in the pembrolizumab/chemo group was nearly double that of the chemo-alone group (55% vs. 29%, P = .0016).
Among 33 patients on the pembrolizumab/chemo combination and 18 on chemo alone who had clinical responses according to independent central review, the median time to response was 1.5 months vs. 2.7 months, respectively. The median duration of response had not been reached in either trial arm at the time of data cutoff, and 88% and 78% of patients, respectively, had ongoing treatment responses.
Progression-free survival, a secondary endpoint, was also significantly better with the combo, with a hazard ratio of 0.53 (P = .0102).
There was no difference in overall survival, however: 75% of patients on the combination were alive at 1 year, compared with 72% of the patients on chemo alone.
Grade 3 or greater treatment-related adverse events were seen in 39% of patients on pembrolizumab, compared with 26% of patients on chemotherapy.
The most common grade 3 or greater adverse events in the combination arm were anemia, decreased neutrophil count, acute kidney injury, decreased lymphocyte count, fatigue, neutropenia, sepsis, and thrombocytopenia. In the chemotherapy-alone group, the most common grade 3 or greater events were anemia, decreased neutrophil count, pancytopenia, and thrombocytopenia.
There were three deaths, one from sepsis each in the pembrolizumab-treated group and chemotherapy alone group, and one from pancytopenia in the chemo alone group.
One (2%) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis, compared with two (3%) of 62 patients in the chemotherapy group.
Invited discussant Jean-Charles Soria, MD, chair of drug development at Gustave Roussy Cancer Center in Paris, said that although the findings of the trial are “intriguing,” there were not enough patients to allow for drawing significant conclusions about the potential use of the combination in clinical practice.
COPENHAGEN – Adding the PD-1 checkpoint inhibitor pembrolizumab (Keytruda) to a standard platinum-doublet chemotherapy regimen nearly doubled response rates among patients with previously untreated advanced nonsquamous non–small cell lung cancer, but did not result in an overall survival advantage, results of a phase II trial show.
After a median follow-up of 10.6 months, the objective response rate among patients randomized to receive carboplatin and pemetrexed plus pembrolizumab was 55%, compared with 29% for patients treated with the platinum doublet alone, reported Corey J. Langer, MD, from the Abramson Cancer Center of the University of Pennsylvania, Philadelphia.
Dr. Langer presented results on one cohort in the KEYNOTE 021 trial, a phase II, randomized, open-label multicohort study looking at pembrolizumab in combination with chemotherapy or immunotherapy.
In this cohort, 123 patients with untreated stage IIIB or IV nonsquamous non–small cell lung cancer with no activating EGFR mutations or ALK translocations were randomly assigned to receive either pembrolizumab 200 mg every 3 weeks for 2 years plus carboplatin dosed to the area under the curve and infused at 5 mg/mL per min plus pemetrexed 500 mg/m2 every 3 weeks for four cycles, or to chemotherapy alone.
Following completion of the trial, patients randomized to chemotherapy could be switched over to pembrolizumab at the same dose and scheduled for up to 2 years.
As noted, for the primary endpoint of confirmed objective response rates, the rate in the pembrolizumab/chemo group was nearly double that of the chemo-alone group (55% vs. 29%, P = .0016).
Among 33 patients on the pembrolizumab/chemo combination and 18 on chemo alone who had clinical responses according to independent central review, the median time to response was 1.5 months vs. 2.7 months, respectively. The median duration of response had not been reached in either trial arm at the time of data cutoff, and 88% and 78% of patients, respectively, had ongoing treatment responses.
Progression-free survival, a secondary endpoint, was also significantly better with the combo, with a hazard ratio of 0.53 (P = .0102).
There was no difference in overall survival, however: 75% of patients on the combination were alive at 1 year, compared with 72% of the patients on chemo alone.
Grade 3 or greater treatment-related adverse events were seen in 39% of patients on pembrolizumab, compared with 26% of patients on chemotherapy.
The most common grade 3 or greater adverse events in the combination arm were anemia, decreased neutrophil count, acute kidney injury, decreased lymphocyte count, fatigue, neutropenia, sepsis, and thrombocytopenia. In the chemotherapy-alone group, the most common grade 3 or greater events were anemia, decreased neutrophil count, pancytopenia, and thrombocytopenia.
There were three deaths, one from sepsis each in the pembrolizumab-treated group and chemotherapy alone group, and one from pancytopenia in the chemo alone group.
One (2%) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis, compared with two (3%) of 62 patients in the chemotherapy group.
Invited discussant Jean-Charles Soria, MD, chair of drug development at Gustave Roussy Cancer Center in Paris, said that although the findings of the trial are “intriguing,” there were not enough patients to allow for drawing significant conclusions about the potential use of the combination in clinical practice.
COPENHAGEN – Adding the PD-1 checkpoint inhibitor pembrolizumab (Keytruda) to a standard platinum-doublet chemotherapy regimen nearly doubled response rates among patients with previously untreated advanced nonsquamous non–small cell lung cancer, but did not result in an overall survival advantage, results of a phase II trial show.
After a median follow-up of 10.6 months, the objective response rate among patients randomized to receive carboplatin and pemetrexed plus pembrolizumab was 55%, compared with 29% for patients treated with the platinum doublet alone, reported Corey J. Langer, MD, from the Abramson Cancer Center of the University of Pennsylvania, Philadelphia.
Dr. Langer presented results on one cohort in the KEYNOTE 021 trial, a phase II, randomized, open-label multicohort study looking at pembrolizumab in combination with chemotherapy or immunotherapy.
In this cohort, 123 patients with untreated stage IIIB or IV nonsquamous non–small cell lung cancer with no activating EGFR mutations or ALK translocations were randomly assigned to receive either pembrolizumab 200 mg every 3 weeks for 2 years plus carboplatin dosed to the area under the curve and infused at 5 mg/mL per min plus pemetrexed 500 mg/m2 every 3 weeks for four cycles, or to chemotherapy alone.
Following completion of the trial, patients randomized to chemotherapy could be switched over to pembrolizumab at the same dose and scheduled for up to 2 years.
As noted, for the primary endpoint of confirmed objective response rates, the rate in the pembrolizumab/chemo group was nearly double that of the chemo-alone group (55% vs. 29%, P = .0016).
Among 33 patients on the pembrolizumab/chemo combination and 18 on chemo alone who had clinical responses according to independent central review, the median time to response was 1.5 months vs. 2.7 months, respectively. The median duration of response had not been reached in either trial arm at the time of data cutoff, and 88% and 78% of patients, respectively, had ongoing treatment responses.
Progression-free survival, a secondary endpoint, was also significantly better with the combo, with a hazard ratio of 0.53 (P = .0102).
There was no difference in overall survival, however: 75% of patients on the combination were alive at 1 year, compared with 72% of the patients on chemo alone.
Grade 3 or greater treatment-related adverse events were seen in 39% of patients on pembrolizumab, compared with 26% of patients on chemotherapy.
The most common grade 3 or greater adverse events in the combination arm were anemia, decreased neutrophil count, acute kidney injury, decreased lymphocyte count, fatigue, neutropenia, sepsis, and thrombocytopenia. In the chemotherapy-alone group, the most common grade 3 or greater events were anemia, decreased neutrophil count, pancytopenia, and thrombocytopenia.
There were three deaths, one from sepsis each in the pembrolizumab-treated group and chemotherapy alone group, and one from pancytopenia in the chemo alone group.
One (2%) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis, compared with two (3%) of 62 patients in the chemotherapy group.
Invited discussant Jean-Charles Soria, MD, chair of drug development at Gustave Roussy Cancer Center in Paris, said that although the findings of the trial are “intriguing,” there were not enough patients to allow for drawing significant conclusions about the potential use of the combination in clinical practice.
Key clinical point: Adding pembrolizumab to platinum-based chemotherapy for upfront therapy of advanced NSCLC nearly doubled response rates.
Major finding: The overall response rate in the pembrolizumab/chemo group was 55% vs. 29% for chemotherapy alone (P = .0016)
Data source: Phase II randomized, open-label trial in 123 patients with untreated stage IIIB or IV nonsquamous NSCLC.
Disclosures: The study was funded by Merck, Sharp, and Dohme. Dr. Langer disclosed research funding from the company. Dr. Soria disclosed financial relationships (consulting/honoraria, research funding) with several companies, but not Merck.
Surgical Risks From Systemic Psoriasis Therapies
I am a coauthor on a recent literature review (J Am Acad Dermatol. 2016;75:798.e7-805.e7) that addressed a common question regarding the use of systemic agents: What should a clinician do if a patient on one of these therapies has an upcoming elective surgery?
Treatment with systemic immunomodulatory agents commonly is employed in patients with moderate to severe plaque psoriasis and psoriatic arthritis. In these individuals, the concern is that surgery may carry an increased risk for infectious or surgical complications. Based on the available literature, my coauthors and I sought to create recommendations for the perioperative management of systemic immunosuppressive therapies in patients with psoriasis and psoriatic arthritis. We conducted a literature review to examine studies that addressed the use of methotrexate, cyclosporine, and biologic agents in patients undergoing surgery. A total of 46 studies were examined, nearly all retrospective studies in patients with inflammatory bowel disease and rheumatoid arthritis.
Based on level III evidence, we concluded that infliximab, adalimumab, etanercept, methotrexate, and cyclosporine can be safely continued through low-risk operations in patients with psoriasis and psoriatic arthritis. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient’s individual risk factors and comorbidities.
What’s the issue?
This study does not provide specific guidelines because of limited and conflicting literature. However, it does provide general guidelines that hopefully will be augmented in the future. How will you handle this situation when it arises in your practice?
I am a coauthor on a recent literature review (J Am Acad Dermatol. 2016;75:798.e7-805.e7) that addressed a common question regarding the use of systemic agents: What should a clinician do if a patient on one of these therapies has an upcoming elective surgery?
Treatment with systemic immunomodulatory agents commonly is employed in patients with moderate to severe plaque psoriasis and psoriatic arthritis. In these individuals, the concern is that surgery may carry an increased risk for infectious or surgical complications. Based on the available literature, my coauthors and I sought to create recommendations for the perioperative management of systemic immunosuppressive therapies in patients with psoriasis and psoriatic arthritis. We conducted a literature review to examine studies that addressed the use of methotrexate, cyclosporine, and biologic agents in patients undergoing surgery. A total of 46 studies were examined, nearly all retrospective studies in patients with inflammatory bowel disease and rheumatoid arthritis.
Based on level III evidence, we concluded that infliximab, adalimumab, etanercept, methotrexate, and cyclosporine can be safely continued through low-risk operations in patients with psoriasis and psoriatic arthritis. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient’s individual risk factors and comorbidities.
What’s the issue?
This study does not provide specific guidelines because of limited and conflicting literature. However, it does provide general guidelines that hopefully will be augmented in the future. How will you handle this situation when it arises in your practice?
I am a coauthor on a recent literature review (J Am Acad Dermatol. 2016;75:798.e7-805.e7) that addressed a common question regarding the use of systemic agents: What should a clinician do if a patient on one of these therapies has an upcoming elective surgery?
Treatment with systemic immunomodulatory agents commonly is employed in patients with moderate to severe plaque psoriasis and psoriatic arthritis. In these individuals, the concern is that surgery may carry an increased risk for infectious or surgical complications. Based on the available literature, my coauthors and I sought to create recommendations for the perioperative management of systemic immunosuppressive therapies in patients with psoriasis and psoriatic arthritis. We conducted a literature review to examine studies that addressed the use of methotrexate, cyclosporine, and biologic agents in patients undergoing surgery. A total of 46 studies were examined, nearly all retrospective studies in patients with inflammatory bowel disease and rheumatoid arthritis.
Based on level III evidence, we concluded that infliximab, adalimumab, etanercept, methotrexate, and cyclosporine can be safely continued through low-risk operations in patients with psoriasis and psoriatic arthritis. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient’s individual risk factors and comorbidities.
What’s the issue?
This study does not provide specific guidelines because of limited and conflicting literature. However, it does provide general guidelines that hopefully will be augmented in the future. How will you handle this situation when it arises in your practice?
Scalp Psoriasis: Weighing Treatment Options
Scalp psoriasis often is the initial presentation of psoriasis, and it can be one of the most challenging aspects of the disease. It can be difficult to treat for several reasons. First, hair can interfere with topical therapy reaching its site of action on the scalp. Second, facial skin also can be exposed to these treatments with the associated risk for adverse events. Finally, compliance often is difficult.
An evidence-based review published online on September 21 in the American Journal of Clinical Dermatology examined treatments for scalp psoriasis, including newer systemic therapies. Of 475 studies initially identified from PubMed and 845 from Embase (up to May 2016), the review included 27 clinical trials, 4 papers reporting pooled analyses of other clinical trials, 10 open-label trials, 1 case series, and 2 case reports after excluding non-English literature.
Wang and Tsai noted that few randomized controlled trials have been performed specifically in scalp psoriasis. The authors found that topical corticosteroids provide good effects and are usually recommended as first-line treatment. Calcipotriol–betamethasone dipropionate is more highly effective than either of its individual components.
The analysis also suggested that localized phototherapy is better than generalized phototherapy on hair-bearing areas. Methotrexate, cyclosporine, fumaric acid esters, and acitretin are well-recognized agents in the treatment of psoriasis, but they located no published randomized controlled trials specifically evaluating these agents in scalp psoriasis. Wang and Tsai also commented that biologics and new small-molecule agents show excellent effects on scalp psoriasis, but the high cost of these treatments mean they may be limited to use in extensive scalp psoriasis. They suggested that more controlled studies are needed for an evidence-based approach to scalp psoriasis.
What’s the issue?
Scalp psoriasis can be an isolated condition or may occur in association with more extensive disease. There has been increased attention to its treatment over the last several years, with several new options. What is your preferred approach to scalp psoriasis?
Scalp psoriasis often is the initial presentation of psoriasis, and it can be one of the most challenging aspects of the disease. It can be difficult to treat for several reasons. First, hair can interfere with topical therapy reaching its site of action on the scalp. Second, facial skin also can be exposed to these treatments with the associated risk for adverse events. Finally, compliance often is difficult.
An evidence-based review published online on September 21 in the American Journal of Clinical Dermatology examined treatments for scalp psoriasis, including newer systemic therapies. Of 475 studies initially identified from PubMed and 845 from Embase (up to May 2016), the review included 27 clinical trials, 4 papers reporting pooled analyses of other clinical trials, 10 open-label trials, 1 case series, and 2 case reports after excluding non-English literature.
Wang and Tsai noted that few randomized controlled trials have been performed specifically in scalp psoriasis. The authors found that topical corticosteroids provide good effects and are usually recommended as first-line treatment. Calcipotriol–betamethasone dipropionate is more highly effective than either of its individual components.
The analysis also suggested that localized phototherapy is better than generalized phototherapy on hair-bearing areas. Methotrexate, cyclosporine, fumaric acid esters, and acitretin are well-recognized agents in the treatment of psoriasis, but they located no published randomized controlled trials specifically evaluating these agents in scalp psoriasis. Wang and Tsai also commented that biologics and new small-molecule agents show excellent effects on scalp psoriasis, but the high cost of these treatments mean they may be limited to use in extensive scalp psoriasis. They suggested that more controlled studies are needed for an evidence-based approach to scalp psoriasis.
What’s the issue?
Scalp psoriasis can be an isolated condition or may occur in association with more extensive disease. There has been increased attention to its treatment over the last several years, with several new options. What is your preferred approach to scalp psoriasis?
Scalp psoriasis often is the initial presentation of psoriasis, and it can be one of the most challenging aspects of the disease. It can be difficult to treat for several reasons. First, hair can interfere with topical therapy reaching its site of action on the scalp. Second, facial skin also can be exposed to these treatments with the associated risk for adverse events. Finally, compliance often is difficult.
An evidence-based review published online on September 21 in the American Journal of Clinical Dermatology examined treatments for scalp psoriasis, including newer systemic therapies. Of 475 studies initially identified from PubMed and 845 from Embase (up to May 2016), the review included 27 clinical trials, 4 papers reporting pooled analyses of other clinical trials, 10 open-label trials, 1 case series, and 2 case reports after excluding non-English literature.
Wang and Tsai noted that few randomized controlled trials have been performed specifically in scalp psoriasis. The authors found that topical corticosteroids provide good effects and are usually recommended as first-line treatment. Calcipotriol–betamethasone dipropionate is more highly effective than either of its individual components.
The analysis also suggested that localized phototherapy is better than generalized phototherapy on hair-bearing areas. Methotrexate, cyclosporine, fumaric acid esters, and acitretin are well-recognized agents in the treatment of psoriasis, but they located no published randomized controlled trials specifically evaluating these agents in scalp psoriasis. Wang and Tsai also commented that biologics and new small-molecule agents show excellent effects on scalp psoriasis, but the high cost of these treatments mean they may be limited to use in extensive scalp psoriasis. They suggested that more controlled studies are needed for an evidence-based approach to scalp psoriasis.
What’s the issue?
Scalp psoriasis can be an isolated condition or may occur in association with more extensive disease. There has been increased attention to its treatment over the last several years, with several new options. What is your preferred approach to scalp psoriasis?