A Zika virus test initially authorized only for emergency use has now been approved for use in nonemergency situations, according to a statement from the Food and Drug Administration.

The ZIKV Detect 2.0 IgM Capture ELISA (enzyme-linked immunosorbent assay) is now authorized for use in patients with clinical signs and symptoms consistent with Zika virus infection, as well as those who meet the Centers for Disease Control and Prevention epidemiologic criteria, including residence in or travel to a region deemed high risk because of active Zika transmission.

The test is designed to identify Zika antibodies in the blood, and the FDA cited a review of clinical trial data and analytic data to support the test’s safety and effectiveness.

“Results of this test are intended to be used in conjunction with clinical observations, patient history, epidemiological information, and other laboratory evidence to make patient management decisions,” the FDA stated.

The ZIKV Detect 2.0 IgM Capture ELISA, initially approved in 2016, had been authorized by the FDA only for emergency use, along with other tests for detecting Zika virus, under the under the FDA’s Emergency Use Authorization (EUA) authority.

The FDA granted marketing authorization to test manufacturer InBios International.

The FDA is communicating with four EUA holders to gather information to evaluate whether the FDA should revoke the EUAs for these specific tests. The marketing authorization of ZIKV Detect 2.0 IgM Capture ELISA does not impact the availability of the other 14 Zika nucleic acid diagnostics available under EUAs.

The Zika virus, typically transmitted by an infected mosquito, is especially a risk for pregnant women as the fetus may experience neurologic complications and microcephaly as a result of infection.

A Zika virus test initially authorized only for emergency use has now been approved for use in nonemergency situations, according to a statement from the Food and Drug Administration.

The ZIKV Detect 2.0 IgM Capture ELISA (enzyme-linked immunosorbent assay) is now authorized for use in patients with clinical signs and symptoms consistent with Zika virus infection, as well as those who meet the Centers for Disease Control and Prevention epidemiologic criteria, including residence in or travel to a region deemed high risk because of active Zika transmission.

The test is designed to identify Zika antibodies in the blood, and the FDA cited a review of clinical trial data and analytic data to support the test’s safety and effectiveness.

“Results of this test are intended to be used in conjunction with clinical observations, patient history, epidemiological information, and other laboratory evidence to make patient management decisions,” the FDA stated.

The ZIKV Detect 2.0 IgM Capture ELISA, initially approved in 2016, had been authorized by the FDA only for emergency use, along with other tests for detecting Zika virus, under the under the FDA’s Emergency Use Authorization (EUA) authority.

The FDA granted marketing authorization to test manufacturer InBios International.

The FDA is communicating with four EUA holders to gather information to evaluate whether the FDA should revoke the EUAs for these specific tests. The marketing authorization of ZIKV Detect 2.0 IgM Capture ELISA does not impact the availability of the other 14 Zika nucleic acid diagnostics available under EUAs.

The Zika virus, typically transmitted by an infected mosquito, is especially a risk for pregnant women as the fetus may experience neurologic complications and microcephaly as a result of infection.

A Zika virus test initially authorized only for emergency use has now been approved for use in nonemergency situations, according to a statement from the Food and Drug Administration.

The ZIKV Detect 2.0 IgM Capture ELISA (enzyme-linked immunosorbent assay) is now authorized for use in patients with clinical signs and symptoms consistent with Zika virus infection, as well as those who meet the Centers for Disease Control and Prevention epidemiologic criteria, including residence in or travel to a region deemed high risk because of active Zika transmission.

The test is designed to identify Zika antibodies in the blood, and the FDA cited a review of clinical trial data and analytic data to support the test’s safety and effectiveness.

“Results of this test are intended to be used in conjunction with clinical observations, patient history, epidemiological information, and other laboratory evidence to make patient management decisions,” the FDA stated.

The ZIKV Detect 2.0 IgM Capture ELISA, initially approved in 2016, had been authorized by the FDA only for emergency use, along with other tests for detecting Zika virus, under the under the FDA’s Emergency Use Authorization (EUA) authority.

The FDA granted marketing authorization to test manufacturer InBios International.

The FDA is communicating with four EUA holders to gather information to evaluate whether the FDA should revoke the EUAs for these specific tests. The marketing authorization of ZIKV Detect 2.0 IgM Capture ELISA does not impact the availability of the other 14 Zika nucleic acid diagnostics available under EUAs.

The Zika virus, typically transmitted by an infected mosquito, is especially a risk for pregnant women as the fetus may experience neurologic complications and microcephaly as a result of infection.

Black men with newly diagnosed nonmetastatic prostate cancer had no significant difference in prostate cancer–specific mortality compared with white men when treated with a standardized approach and follow-up or at a health care system with standardized access, according to recent research published in JAMA Oncology.

Robert T. Dess, MD, from the department of radiation oncology at the University of Michigan, Ann Arbor, and colleagues examined data from 296,273 patients in the Surveillance, Epidemiology, and End Results (SEER) cohort, 3,972 patients from the Veterans Affairs (VA) health system, and 5,854 patients in four randomized controlled trials (RCTs) from the National Cancer Institute–sponsored Radiation Therapy Oncology Group between January 1992 and December 2013. Of these, 52,840 patients (17.8%) in the SEER cohort, 1,513 patients (38.1%) in the VA cohort, and 1,129 (19.3%) in the RCT cohort were black men. The mean age across all cohorts was 64.9 years, and the median follow-up was 75 months in the SEER cohort, 97 months in the VA cohort, and 104 months in the RCT cohort.

After adjustment for age in the SEER cohort, black men had a 30% increased risk of prostate cancer–specific mortality (PCSM) compared with white men (subdistribution hazard ratio, 1.30; 95% CI, 1.23-1.37; P less than .001). However, after the researchers performed inverse probability weighting (IPW) to adjust for race-based imbalances such as access to care and standardized treatment, there was a 0.5% increased risk over 10 years (sHR, 1.09; 95% CI, 1.04-1.15; P less than .001) after diagnosis.

In the VA cohort, IPW yielded no significant differences between black men and white men (sHR, 0.85; 95% CI, 0.56-1.30; P = .46), and there was a significantly lower risk for black men in the RCT cohort after IPW (sHR, 0.81; 95% CI, 0.66-0.99; P = .04). With regard to other outcomes, other-cause mortality was significantly higher for black men in the SEER cohort (sHR, 1.30; 95% CI, 1.27-1.34; P less than .001) and in the RCT cohort (sHR, 1.17; 95% CI, 1.06-1.29; P = .002) after IPW.

“Black race remains associated with many factors that negatively affect outcomes, and disparities persist at the population level,” Dr. Dess and colleagues wrote in their study. “Continued efforts are needed to address this clear racial health inequity driven by modifiable nonbiological risk factors.”

The researchers said some residual confounding may exist, but noted the strengths of the study included a diverse cohort with a large range of treatment approaches.

This study was funded in part by the Prostate Cancer Foundation, a grant from the Prostate Cancer National Institutes of Health Specialized Programs of Research Excellence, two grants from the Department of Defense, a grant from NIH, and a grant from the NIH Cancer Center. One or more of the authors reported relationships in the form of grants, personal fees, and consulting fees with numerous companies. The other authors report no relevant conflicts of interest.

SOURCE: Dess RT et al. JAMA Oncol. 2019 May 23. doi: 10.1001/jamaoncol.2019.0826.

Black men with newly diagnosed nonmetastatic prostate cancer had no significant difference in prostate cancer–specific mortality compared with white men when treated with a standardized approach and follow-up or at a health care system with standardized access, according to recent research published in JAMA Oncology.

Robert T. Dess, MD, from the department of radiation oncology at the University of Michigan, Ann Arbor, and colleagues examined data from 296,273 patients in the Surveillance, Epidemiology, and End Results (SEER) cohort, 3,972 patients from the Veterans Affairs (VA) health system, and 5,854 patients in four randomized controlled trials (RCTs) from the National Cancer Institute–sponsored Radiation Therapy Oncology Group between January 1992 and December 2013. Of these, 52,840 patients (17.8%) in the SEER cohort, 1,513 patients (38.1%) in the VA cohort, and 1,129 (19.3%) in the RCT cohort were black men. The mean age across all cohorts was 64.9 years, and the median follow-up was 75 months in the SEER cohort, 97 months in the VA cohort, and 104 months in the RCT cohort.

After adjustment for age in the SEER cohort, black men had a 30% increased risk of prostate cancer–specific mortality (PCSM) compared with white men (subdistribution hazard ratio, 1.30; 95% CI, 1.23-1.37; P less than .001). However, after the researchers performed inverse probability weighting (IPW) to adjust for race-based imbalances such as access to care and standardized treatment, there was a 0.5% increased risk over 10 years (sHR, 1.09; 95% CI, 1.04-1.15; P less than .001) after diagnosis.

In the VA cohort, IPW yielded no significant differences between black men and white men (sHR, 0.85; 95% CI, 0.56-1.30; P = .46), and there was a significantly lower risk for black men in the RCT cohort after IPW (sHR, 0.81; 95% CI, 0.66-0.99; P = .04). With regard to other outcomes, other-cause mortality was significantly higher for black men in the SEER cohort (sHR, 1.30; 95% CI, 1.27-1.34; P less than .001) and in the RCT cohort (sHR, 1.17; 95% CI, 1.06-1.29; P = .002) after IPW.

“Black race remains associated with many factors that negatively affect outcomes, and disparities persist at the population level,” Dr. Dess and colleagues wrote in their study. “Continued efforts are needed to address this clear racial health inequity driven by modifiable nonbiological risk factors.”

The researchers said some residual confounding may exist, but noted the strengths of the study included a diverse cohort with a large range of treatment approaches.

This study was funded in part by the Prostate Cancer Foundation, a grant from the Prostate Cancer National Institutes of Health Specialized Programs of Research Excellence, two grants from the Department of Defense, a grant from NIH, and a grant from the NIH Cancer Center. One or more of the authors reported relationships in the form of grants, personal fees, and consulting fees with numerous companies. The other authors report no relevant conflicts of interest.

SOURCE: Dess RT et al. JAMA Oncol. 2019 May 23. doi: 10.1001/jamaoncol.2019.0826.

Black men with newly diagnosed nonmetastatic prostate cancer had no significant difference in prostate cancer–specific mortality compared with white men when treated with a standardized approach and follow-up or at a health care system with standardized access, according to recent research published in JAMA Oncology.

Robert T. Dess, MD, from the department of radiation oncology at the University of Michigan, Ann Arbor, and colleagues examined data from 296,273 patients in the Surveillance, Epidemiology, and End Results (SEER) cohort, 3,972 patients from the Veterans Affairs (VA) health system, and 5,854 patients in four randomized controlled trials (RCTs) from the National Cancer Institute–sponsored Radiation Therapy Oncology Group between January 1992 and December 2013. Of these, 52,840 patients (17.8%) in the SEER cohort, 1,513 patients (38.1%) in the VA cohort, and 1,129 (19.3%) in the RCT cohort were black men. The mean age across all cohorts was 64.9 years, and the median follow-up was 75 months in the SEER cohort, 97 months in the VA cohort, and 104 months in the RCT cohort.

After adjustment for age in the SEER cohort, black men had a 30% increased risk of prostate cancer–specific mortality (PCSM) compared with white men (subdistribution hazard ratio, 1.30; 95% CI, 1.23-1.37; P less than .001). However, after the researchers performed inverse probability weighting (IPW) to adjust for race-based imbalances such as access to care and standardized treatment, there was a 0.5% increased risk over 10 years (sHR, 1.09; 95% CI, 1.04-1.15; P less than .001) after diagnosis.

In the VA cohort, IPW yielded no significant differences between black men and white men (sHR, 0.85; 95% CI, 0.56-1.30; P = .46), and there was a significantly lower risk for black men in the RCT cohort after IPW (sHR, 0.81; 95% CI, 0.66-0.99; P = .04). With regard to other outcomes, other-cause mortality was significantly higher for black men in the SEER cohort (sHR, 1.30; 95% CI, 1.27-1.34; P less than .001) and in the RCT cohort (sHR, 1.17; 95% CI, 1.06-1.29; P = .002) after IPW.

“Black race remains associated with many factors that negatively affect outcomes, and disparities persist at the population level,” Dr. Dess and colleagues wrote in their study. “Continued efforts are needed to address this clear racial health inequity driven by modifiable nonbiological risk factors.”

The researchers said some residual confounding may exist, but noted the strengths of the study included a diverse cohort with a large range of treatment approaches.

This study was funded in part by the Prostate Cancer Foundation, a grant from the Prostate Cancer National Institutes of Health Specialized Programs of Research Excellence, two grants from the Department of Defense, a grant from NIH, and a grant from the NIH Cancer Center. One or more of the authors reported relationships in the form of grants, personal fees, and consulting fees with numerous companies. The other authors report no relevant conflicts of interest.

SOURCE: Dess RT et al. JAMA Oncol. 2019 May 23. doi: 10.1001/jamaoncol.2019.0826.

TORONTO – The use of warfarin or related vitamin K antagonists was associated with a more than 100% increased risk of incident or progressive knee or hip osteoarthritis in the Rotterdam Study, Cindy G. Boer reported at the OARSI 2019 World Congress.

A biologically plausible mechanism exists for this relationship, added Ms. Boer, a PhD student with a special interest in the molecular genetics of OA at Erasmus University, Rotterdam, the Netherlands.

Bruce Jancin/MDedge News

About 80% of the OA endpoints in this analysis involved incident OA, defined radiographically as Kellgren-Lawrence grade 2. Progressive OA was defined as going from grade 2 at baseline to grade 3-4 during follow-up.

There was a signal of a treatment duration-related effect, with OA rates trending highest in individuals on warfarin for longer than 365 days, followed by those on the oral anticoagulant for more than 100 days, who in turn had higher rates than those on warfarin for less time.

Ms. Boer said an important next step in this research is to replicate the warfarin/OA association in an independent cohort. Also, she and her coworkers are now gathering OA incidence and progression data in patients on direct oral anticoagulants rather than warfarin to test the hypothesis that they will not have an increased rate of OA, compared with nonusers, since these newer agents don’t affect vitamin K. Of course, if they do turn out to have an elevated risk, it would point to one or more of the conditions for which oral anticoagulants are commonly prescribed as the explanation.

She reported having no financial conflicts regarding her study, sponsored by Erasmus University and the Dutch government.

bjancin@mdedge.com

TORONTO – The use of warfarin or related vitamin K antagonists was associated with a more than 100% increased risk of incident or progressive knee or hip osteoarthritis in the Rotterdam Study, Cindy G. Boer reported at the OARSI 2019 World Congress.

A biologically plausible mechanism exists for this relationship, added Ms. Boer, a PhD student with a special interest in the molecular genetics of OA at Erasmus University, Rotterdam, the Netherlands.

Bruce Jancin/MDedge News

About 80% of the OA endpoints in this analysis involved incident OA, defined radiographically as Kellgren-Lawrence grade 2. Progressive OA was defined as going from grade 2 at baseline to grade 3-4 during follow-up.

There was a signal of a treatment duration-related effect, with OA rates trending highest in individuals on warfarin for longer than 365 days, followed by those on the oral anticoagulant for more than 100 days, who in turn had higher rates than those on warfarin for less time.

Ms. Boer said an important next step in this research is to replicate the warfarin/OA association in an independent cohort. Also, she and her coworkers are now gathering OA incidence and progression data in patients on direct oral anticoagulants rather than warfarin to test the hypothesis that they will not have an increased rate of OA, compared with nonusers, since these newer agents don’t affect vitamin K. Of course, if they do turn out to have an elevated risk, it would point to one or more of the conditions for which oral anticoagulants are commonly prescribed as the explanation.

She reported having no financial conflicts regarding her study, sponsored by Erasmus University and the Dutch government.

bjancin@mdedge.com

TORONTO – The use of warfarin or related vitamin K antagonists was associated with a more than 100% increased risk of incident or progressive knee or hip osteoarthritis in the Rotterdam Study, Cindy G. Boer reported at the OARSI 2019 World Congress.

A biologically plausible mechanism exists for this relationship, added Ms. Boer, a PhD student with a special interest in the molecular genetics of OA at Erasmus University, Rotterdam, the Netherlands.

Bruce Jancin/MDedge News

About 80% of the OA endpoints in this analysis involved incident OA, defined radiographically as Kellgren-Lawrence grade 2. Progressive OA was defined as going from grade 2 at baseline to grade 3-4 during follow-up.

There was a signal of a treatment duration-related effect, with OA rates trending highest in individuals on warfarin for longer than 365 days, followed by those on the oral anticoagulant for more than 100 days, who in turn had higher rates than those on warfarin for less time.

Ms. Boer said an important next step in this research is to replicate the warfarin/OA association in an independent cohort. Also, she and her coworkers are now gathering OA incidence and progression data in patients on direct oral anticoagulants rather than warfarin to test the hypothesis that they will not have an increased rate of OA, compared with nonusers, since these newer agents don’t affect vitamin K. Of course, if they do turn out to have an elevated risk, it would point to one or more of the conditions for which oral anticoagulants are commonly prescribed as the explanation.

She reported having no financial conflicts regarding her study, sponsored by Erasmus University and the Dutch government.

bjancin@mdedge.com

Clinical question: Does using a restrictive transfusion strategy with patients undergoing cardiac surgery affect long-term outcomes?

Background: Using a restrictive transfusion strategy in patients undergoing cardiac surgery is known to use fewer units of allogeneic red cells, compared with a liberal strategy, while still having noninferior short-term clinical outcomes. At this time, little is known about such a strategy’s long-term effects.

Study design: Randomized, open-label, noninferiority trial.

Setting: 74 hospitals in 19 countries.

Synopsis: 5,243 adults undergoing nontransplant cardiac surgeries and having at least a moderate predicted risk for death were randomly divided into a liberal or restrictive transfusion strategy. Restrictive-­strategy participants received a transfusion when hemoglobin was less than 7.5 g/dL, compared with either a hemoglobin of 8.5 g/dL on the floor or 9.5 g/dL in the ICU for the liberal-strategy group. During the hospitalization, the restrictive group received fewer U of red cells and had a lower mean predischarge hemoglobin. At 6 months, the groups were compared for the primary outcomes of death, MI, stroke, or renal failure requiring dialysis, finding an occurrence of such in 402/2,317 in the restrictive-strategy group and 402/2,347 in the liberal-strategy group (P = .006 for noninferiority). Limitations include the study being a noninferiority trial and the very specific patient population selected.

Bottom line: In patients undergoing cardiac surgery, a restrictive transfusion strategy is noninferior to a liberal strategy with respect to death from any cause, MI, stroke, and new renal failure requiring dialysis at 6 months postop.

Citation: Mazer CD et al. Six-month outcomes after restrictive or liberal transfusion for cardiac surgery. N Eng J Med. 2018 Sep 27;379(13):1224-33.

Dr. Shaw is an assistant professor in the division of hospital medicine,University of New Mexico.

Clinical question: Does using a restrictive transfusion strategy with patients undergoing cardiac surgery affect long-term outcomes?

Background: Using a restrictive transfusion strategy in patients undergoing cardiac surgery is known to use fewer units of allogeneic red cells, compared with a liberal strategy, while still having noninferior short-term clinical outcomes. At this time, little is known about such a strategy’s long-term effects.

Study design: Randomized, open-label, noninferiority trial.

Setting: 74 hospitals in 19 countries.

Synopsis: 5,243 adults undergoing nontransplant cardiac surgeries and having at least a moderate predicted risk for death were randomly divided into a liberal or restrictive transfusion strategy. Restrictive-­strategy participants received a transfusion when hemoglobin was less than 7.5 g/dL, compared with either a hemoglobin of 8.5 g/dL on the floor or 9.5 g/dL in the ICU for the liberal-strategy group. During the hospitalization, the restrictive group received fewer U of red cells and had a lower mean predischarge hemoglobin. At 6 months, the groups were compared for the primary outcomes of death, MI, stroke, or renal failure requiring dialysis, finding an occurrence of such in 402/2,317 in the restrictive-strategy group and 402/2,347 in the liberal-strategy group (P = .006 for noninferiority). Limitations include the study being a noninferiority trial and the very specific patient population selected.

Bottom line: In patients undergoing cardiac surgery, a restrictive transfusion strategy is noninferior to a liberal strategy with respect to death from any cause, MI, stroke, and new renal failure requiring dialysis at 6 months postop.

Citation: Mazer CD et al. Six-month outcomes after restrictive or liberal transfusion for cardiac surgery. N Eng J Med. 2018 Sep 27;379(13):1224-33.

Dr. Shaw is an assistant professor in the division of hospital medicine,University of New Mexico.

Clinical question: Does using a restrictive transfusion strategy with patients undergoing cardiac surgery affect long-term outcomes?

Background: Using a restrictive transfusion strategy in patients undergoing cardiac surgery is known to use fewer units of allogeneic red cells, compared with a liberal strategy, while still having noninferior short-term clinical outcomes. At this time, little is known about such a strategy’s long-term effects.

Study design: Randomized, open-label, noninferiority trial.

Setting: 74 hospitals in 19 countries.

Synopsis: 5,243 adults undergoing nontransplant cardiac surgeries and having at least a moderate predicted risk for death were randomly divided into a liberal or restrictive transfusion strategy. Restrictive-­strategy participants received a transfusion when hemoglobin was less than 7.5 g/dL, compared with either a hemoglobin of 8.5 g/dL on the floor or 9.5 g/dL in the ICU for the liberal-strategy group. During the hospitalization, the restrictive group received fewer U of red cells and had a lower mean predischarge hemoglobin. At 6 months, the groups were compared for the primary outcomes of death, MI, stroke, or renal failure requiring dialysis, finding an occurrence of such in 402/2,317 in the restrictive-strategy group and 402/2,347 in the liberal-strategy group (P = .006 for noninferiority). Limitations include the study being a noninferiority trial and the very specific patient population selected.

Bottom line: In patients undergoing cardiac surgery, a restrictive transfusion strategy is noninferior to a liberal strategy with respect to death from any cause, MI, stroke, and new renal failure requiring dialysis at 6 months postop.

Citation: Mazer CD et al. Six-month outcomes after restrictive or liberal transfusion for cardiac surgery. N Eng J Med. 2018 Sep 27;379(13):1224-33.

Dr. Shaw is an assistant professor in the division of hospital medicine,University of New Mexico.

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The Food and Drug Administration has granted its first marketing clearance for extragenital diagnostic tests for chlamydia and gonorrhea.

The new tests, the Aptima Combo 2 Assay and Xpert CT/NG, use samples from the throat and rectum to test for chlamydia and gonorrhea, according to a statement from the FDA.

“It is best for patients if both [chlamydia and gonorrhea] are caught and treated right away, as significant complications can occur if left untreated,” noted Tim Stenzel, MD, in the statement.

“Today’s clearances provide a mechanism for more easily diagnosing these infections,” said Dr. Stenzel, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health.

The two tests were reviewed through the premarket notification – or 510(k) – pathway, which seeks to demonstrate to the FDA that the device to be marketed is equivalent or better in safety and effectiveness to the legally marketed device.

In the FDA’s evaluation of the tests, it reviewed clinical data from a multisite study of more than 2,500 patients. This study evaluated the diagnostic accuracy of multiple commercially available nucleic acid amplification tests for detection of Neisseria gonorrhoeae and Chlamydia trachomatis from throat and rectal sites. The results of this study and other information reviewed by the FDA demonstrated that the two tests “are safe and effective for extragenital testing for chlamydia and gonorrhea,” according to the statement.

The data were collected through a cross-sectional study coordinated by the Antibacterial Resistance Leadership Group, which is funded and supported by the National Institute of Allergy and Infectious Diseases.

The FDA granted marketing clearance to Hologic and Cepheid for the Aptima Combo 2 Assay and the Xpert CT/NG, respectively.
 

klennon@mdedge.com

The Food and Drug Administration has granted its first marketing clearance for extragenital diagnostic tests for chlamydia and gonorrhea.

The new tests, the Aptima Combo 2 Assay and Xpert CT/NG, use samples from the throat and rectum to test for chlamydia and gonorrhea, according to a statement from the FDA.

“It is best for patients if both [chlamydia and gonorrhea] are caught and treated right away, as significant complications can occur if left untreated,” noted Tim Stenzel, MD, in the statement.

“Today’s clearances provide a mechanism for more easily diagnosing these infections,” said Dr. Stenzel, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health.

The two tests were reviewed through the premarket notification – or 510(k) – pathway, which seeks to demonstrate to the FDA that the device to be marketed is equivalent or better in safety and effectiveness to the legally marketed device.

In the FDA’s evaluation of the tests, it reviewed clinical data from a multisite study of more than 2,500 patients. This study evaluated the diagnostic accuracy of multiple commercially available nucleic acid amplification tests for detection of Neisseria gonorrhoeae and Chlamydia trachomatis from throat and rectal sites. The results of this study and other information reviewed by the FDA demonstrated that the two tests “are safe and effective for extragenital testing for chlamydia and gonorrhea,” according to the statement.

The data were collected through a cross-sectional study coordinated by the Antibacterial Resistance Leadership Group, which is funded and supported by the National Institute of Allergy and Infectious Diseases.

The FDA granted marketing clearance to Hologic and Cepheid for the Aptima Combo 2 Assay and the Xpert CT/NG, respectively.
 

klennon@mdedge.com

The Food and Drug Administration has granted its first marketing clearance for extragenital diagnostic tests for chlamydia and gonorrhea.

The new tests, the Aptima Combo 2 Assay and Xpert CT/NG, use samples from the throat and rectum to test for chlamydia and gonorrhea, according to a statement from the FDA.

“It is best for patients if both [chlamydia and gonorrhea] are caught and treated right away, as significant complications can occur if left untreated,” noted Tim Stenzel, MD, in the statement.

“Today’s clearances provide a mechanism for more easily diagnosing these infections,” said Dr. Stenzel, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health.

The two tests were reviewed through the premarket notification – or 510(k) – pathway, which seeks to demonstrate to the FDA that the device to be marketed is equivalent or better in safety and effectiveness to the legally marketed device.

In the FDA’s evaluation of the tests, it reviewed clinical data from a multisite study of more than 2,500 patients. This study evaluated the diagnostic accuracy of multiple commercially available nucleic acid amplification tests for detection of Neisseria gonorrhoeae and Chlamydia trachomatis from throat and rectal sites. The results of this study and other information reviewed by the FDA demonstrated that the two tests “are safe and effective for extragenital testing for chlamydia and gonorrhea,” according to the statement.

The data were collected through a cross-sectional study coordinated by the Antibacterial Resistance Leadership Group, which is funded and supported by the National Institute of Allergy and Infectious Diseases.

The FDA granted marketing clearance to Hologic and Cepheid for the Aptima Combo 2 Assay and the Xpert CT/NG, respectively.
 

klennon@mdedge.com

House Budget Committee Chairman John Yarmuth (D-Ky.) opened a May 22 hearing on the prospect of moving to some kind of single-payer health care system with a bold prediction.

“I strongly believe it’s not a matter of if we will have universal coverage, but when,” Rep. Yarmuth said, adding that the “trick is closing the information gap on what single-payer health care truly is, so that we can close the health coverage gap for millions of American families.”

The hearing was held to review a Congressional Budget Office report ordered by Chairman Yarmuth, which examines the key design elements to be considered in establishing a single-payer system.

Mark Hadley, deputy director of the Congressional Budget Office, highlighted two key points with regard to establishing a single-payer system.

“First, moving to a single-payer system would be a major undertaking,” he said. “It would involve significant changes for all participants – individuals, providers, insurers, employers, and manufacturers of drugs and medical devices. Because health care spending currently accounts for about one-sixth of the nation’s economic activity, those changes could significantly affect the overall U.S. economy. And the transition toward a single-payer system could be complicated, challenging, and potentially disruptive.”

Mr. Hadley continued: “Second, to establish a single-payer system, lawmakers would need to make many decisions and would face complex trade-offs.”

And because of the multitude of trade-offs related to the design of a single-payer system, questions related to coverage, cost, and access to health care services were generally met with vague answers.

For example, would a single-payer system create access issues because of the potential increased burden on providers by providing health care coverage to all?

“Whether the supply of providers would be adequate to meet the greater demand would depend on various components of the system,” Mr. Hadley said. “If the supply of services was not sufficient to meet the demand for care, patients might face increased wait times and reduced access to care. The government, however, could implement policies to encourage the provision of services, and in the longer run, providers might deliver care more efficiently.”

Republican lawmakers on the panel focused on a detail lacking in the report: a cost estimate for implementing a single-payer system.

“What’s noticeably missing from the report is a cost estimate for specific proposals,” said Rep. Steve Womack (R-Ark.), the committee’s ranking member. “My friends across the aisle didn’t ask for one. I think I know why. While the score would be useful, we already know how much a one-size-fits-all health care system would cost the American people. Independent analyses from economists across the ideological spectrum, including George Mason University, the Urban Institute, [and] the American Action Forum have projected single-payer type proposals, such as Medicare-for-all, to cost at least $32 trillion.”

Rep. Womack also said that the report “has been especially helpful in showing that these ideas will never work in America.”

He noted that the report warns that a single-payer system could end up “reducing payment rates for providers. That is payments for doctors, hospitals, and so on. The report explains there will not only be a reduction in the quality of care, there would be a reduction in the supply of care, hampering access to the treatments and services people need.”

The report does caution that using cost-containment measures, such as global budgets and utilization management, “could adversely affect access to and quality of care by causing providers to supply less care to patients covered by the public plan. Less spending on medical services could also alter manufacturers’ incentive to develop new technologies or providers’ incentive to invest in capital, which could affect patients’ choices over the long term.”

Additionally, the report notes that the structure of a single-payer system could result in lower reimbursement for health care services. “Proposals like Medicare-for-all will chase a lot of doctors out of health care,” Rep. Womack said.

gtwachtman@mdedge.com

House Budget Committee Chairman John Yarmuth (D-Ky.) opened a May 22 hearing on the prospect of moving to some kind of single-payer health care system with a bold prediction.

“I strongly believe it’s not a matter of if we will have universal coverage, but when,” Rep. Yarmuth said, adding that the “trick is closing the information gap on what single-payer health care truly is, so that we can close the health coverage gap for millions of American families.”

The hearing was held to review a Congressional Budget Office report ordered by Chairman Yarmuth, which examines the key design elements to be considered in establishing a single-payer system.

Mark Hadley, deputy director of the Congressional Budget Office, highlighted two key points with regard to establishing a single-payer system.

“First, moving to a single-payer system would be a major undertaking,” he said. “It would involve significant changes for all participants – individuals, providers, insurers, employers, and manufacturers of drugs and medical devices. Because health care spending currently accounts for about one-sixth of the nation’s economic activity, those changes could significantly affect the overall U.S. economy. And the transition toward a single-payer system could be complicated, challenging, and potentially disruptive.”

Mr. Hadley continued: “Second, to establish a single-payer system, lawmakers would need to make many decisions and would face complex trade-offs.”

And because of the multitude of trade-offs related to the design of a single-payer system, questions related to coverage, cost, and access to health care services were generally met with vague answers.

For example, would a single-payer system create access issues because of the potential increased burden on providers by providing health care coverage to all?

“Whether the supply of providers would be adequate to meet the greater demand would depend on various components of the system,” Mr. Hadley said. “If the supply of services was not sufficient to meet the demand for care, patients might face increased wait times and reduced access to care. The government, however, could implement policies to encourage the provision of services, and in the longer run, providers might deliver care more efficiently.”

Republican lawmakers on the panel focused on a detail lacking in the report: a cost estimate for implementing a single-payer system.

“What’s noticeably missing from the report is a cost estimate for specific proposals,” said Rep. Steve Womack (R-Ark.), the committee’s ranking member. “My friends across the aisle didn’t ask for one. I think I know why. While the score would be useful, we already know how much a one-size-fits-all health care system would cost the American people. Independent analyses from economists across the ideological spectrum, including George Mason University, the Urban Institute, [and] the American Action Forum have projected single-payer type proposals, such as Medicare-for-all, to cost at least $32 trillion.”

Rep. Womack also said that the report “has been especially helpful in showing that these ideas will never work in America.”

He noted that the report warns that a single-payer system could end up “reducing payment rates for providers. That is payments for doctors, hospitals, and so on. The report explains there will not only be a reduction in the quality of care, there would be a reduction in the supply of care, hampering access to the treatments and services people need.”

The report does caution that using cost-containment measures, such as global budgets and utilization management, “could adversely affect access to and quality of care by causing providers to supply less care to patients covered by the public plan. Less spending on medical services could also alter manufacturers’ incentive to develop new technologies or providers’ incentive to invest in capital, which could affect patients’ choices over the long term.”

Additionally, the report notes that the structure of a single-payer system could result in lower reimbursement for health care services. “Proposals like Medicare-for-all will chase a lot of doctors out of health care,” Rep. Womack said.

gtwachtman@mdedge.com

House Budget Committee Chairman John Yarmuth (D-Ky.) opened a May 22 hearing on the prospect of moving to some kind of single-payer health care system with a bold prediction.

“I strongly believe it’s not a matter of if we will have universal coverage, but when,” Rep. Yarmuth said, adding that the “trick is closing the information gap on what single-payer health care truly is, so that we can close the health coverage gap for millions of American families.”

The hearing was held to review a Congressional Budget Office report ordered by Chairman Yarmuth, which examines the key design elements to be considered in establishing a single-payer system.

Mark Hadley, deputy director of the Congressional Budget Office, highlighted two key points with regard to establishing a single-payer system.

“First, moving to a single-payer system would be a major undertaking,” he said. “It would involve significant changes for all participants – individuals, providers, insurers, employers, and manufacturers of drugs and medical devices. Because health care spending currently accounts for about one-sixth of the nation’s economic activity, those changes could significantly affect the overall U.S. economy. And the transition toward a single-payer system could be complicated, challenging, and potentially disruptive.”

Mr. Hadley continued: “Second, to establish a single-payer system, lawmakers would need to make many decisions and would face complex trade-offs.”

And because of the multitude of trade-offs related to the design of a single-payer system, questions related to coverage, cost, and access to health care services were generally met with vague answers.

For example, would a single-payer system create access issues because of the potential increased burden on providers by providing health care coverage to all?

“Whether the supply of providers would be adequate to meet the greater demand would depend on various components of the system,” Mr. Hadley said. “If the supply of services was not sufficient to meet the demand for care, patients might face increased wait times and reduced access to care. The government, however, could implement policies to encourage the provision of services, and in the longer run, providers might deliver care more efficiently.”

Republican lawmakers on the panel focused on a detail lacking in the report: a cost estimate for implementing a single-payer system.

“What’s noticeably missing from the report is a cost estimate for specific proposals,” said Rep. Steve Womack (R-Ark.), the committee’s ranking member. “My friends across the aisle didn’t ask for one. I think I know why. While the score would be useful, we already know how much a one-size-fits-all health care system would cost the American people. Independent analyses from economists across the ideological spectrum, including George Mason University, the Urban Institute, [and] the American Action Forum have projected single-payer type proposals, such as Medicare-for-all, to cost at least $32 trillion.”

Rep. Womack also said that the report “has been especially helpful in showing that these ideas will never work in America.”

He noted that the report warns that a single-payer system could end up “reducing payment rates for providers. That is payments for doctors, hospitals, and so on. The report explains there will not only be a reduction in the quality of care, there would be a reduction in the supply of care, hampering access to the treatments and services people need.”

The report does caution that using cost-containment measures, such as global budgets and utilization management, “could adversely affect access to and quality of care by causing providers to supply less care to patients covered by the public plan. Less spending on medical services could also alter manufacturers’ incentive to develop new technologies or providers’ incentive to invest in capital, which could affect patients’ choices over the long term.”

Additionally, the report notes that the structure of a single-payer system could result in lower reimbursement for health care services. “Proposals like Medicare-for-all will chase a lot of doctors out of health care,” Rep. Womack said.

gtwachtman@mdedge.com

SAN DIEGO – Waiting to perform cholecystectomy after mild biliary pancreatitis was associated with an increased risk of recurrent biliary events in a recent study. In a retrospective study of 234 patients admitted for gallstone pancreatitis, almost 90% of recurrent biliary events occurred in patients who did not receive a cholecystectomy within 60 days of hospital discharge. The overall rate of recurrence was 19%, and over half of patients (59%) did not receive a cholecystectomy during their index hospitalization.

Dmitrii Kotin/Thinkstock.com

Additionally, none of the recurrent biliary events occurred in those patients who did receive a cholecystectomy during the index hospitalization or within the first 30 days after discharge. “It really is the case that, ‘if you snooze, you lose,’ ” said Vijay Dalapathi, MD, presenting the findings during an oral presentation at the annual Digestive Disease Week.

Dr. Dalapathi and colleagues had observed that cholecystectomy during an index hospitalization for mild biliary pancreatitis was a far from universal practice, despite guidelines recommending early cholecystectomy.

To delve further into practice patterns, Dr. Dalapathi, first author Mohammed Ullah, MD, and their coauthors at the University of Rochester (N.Y.) conducted a single-site retrospective study of patients who were admitted with gallstone pancreatitis over a 5-year period ending December 2017. Dr. Dalapathi and Dr. Ullah are both second-year gastroenterology fellows.

The study had twin primary outcome measures: cholecystectomy rates performed during an index hospitalization for gallstone pancreatitis and recurrent biliary events after hospitalization. Adult patients were included if they had a diagnosis of acute gallstone pancreatitis, with or without recurrent cholangitis, choledocholithiasis, or acute cholecystitis. Pediatric patients and those with prior cholecystectomy were excluded.

A total of 234 patients were included in the study. Their mean age was 58.3 years, and patients were mostly female (57.3%) and white (91.5%). Mean body mass index was 29.1 kg/m². A total of 175 patients (74.8%) had endoscopic retrograde cholangiopancreatography.

Out of the entire cohort of patients, 138 (59%) did not have a cholecystectomy during the index hospitalization. Among the patients who did not receive a cholecystectomy, 33 (24%) were deemed unsuitable candidates for the procedure, either because they were critically ill or because they were poor candidates for surgery for other reasons. No reason was provided for the nonperformance of cholecystectomy for an additional 28 patients (20%).

The remaining 75 patients (54%) were deferred to outpatient management. Looking at this subgroup of patients, Dr. Dalapathi and his coinvestigators tracked the amount of time that passed before cholecystectomy.

The researchers found that 19 patients (25%) had not had a cholecystectomy within the study period. A total of 21 patients (28%) had the procedure more than 60 days from hospitalization, and another 23 (31%) had the procedure between 30 and 60 days after hospitalization. Just 12 patients (16%) of this subgroup had their cholecystectomy within 30 days of hospitalization.

Among patients who were discharged without a cholecystectomy, Dr. Dalapathi and his coauthors found 26 recurrent biliary events (19%): 15 were gallstone pancreatitis and 10 were cholecystitis; 1 patient developed cholangitis.

The crux of the study’s findings came when the investigators looked at the association between recurrent events and cholecystectomy timing. They found no recurrent biliary events among those who received cholecystectomy while hospitalized or within the first 30 days after discharge. Of the 26 events, 3 (12%) occurred in those whose cholecystectomies came 30-60 days after discharge. The remaining 23 events (88%) were seen in those receiving a cholecystectomy more than 60 days after discharge, or not at all.

Guidelines from the American Gastroenterological Association, the Society of American Gastrointestinal and Endoscopic Surgeons, and the American College of Gastroenterology all recommend early cholecystectomy after mild acute gallstone pancreatitis, said Dr. Dalapathi.

However, two separate systematic reviews including a total of 22 studies and over 3,000 patients showed that about half (48% and 51%) of patients admitted with mild acute biliary pancreatitis received a cholecystectomy during the index hospitalization or within 14 days of the hospitalization.

Further, he said, previous work had shown recurrent biliary event rates approaching 20% for patients whose biliary pancreatitis bout was not followed by cholecystectomy, a figure in line with the rate seen in the present study.

“Cholecystectomy should be performed during index hospitalization or as soon as possible within 30 days of mild biliary pancreatitis to minimize risk of recurrent biliary events,” said Dr. Dalapathi.

The authors reported no outside sources of funding and no conflicts of interest.

koakes@mdedge.com

SOURCE: Ullah M. et al. DDW 2019, Abstract 24.

SAN DIEGO – Waiting to perform cholecystectomy after mild biliary pancreatitis was associated with an increased risk of recurrent biliary events in a recent study. In a retrospective study of 234 patients admitted for gallstone pancreatitis, almost 90% of recurrent biliary events occurred in patients who did not receive a cholecystectomy within 60 days of hospital discharge. The overall rate of recurrence was 19%, and over half of patients (59%) did not receive a cholecystectomy during their index hospitalization.

Dmitrii Kotin/Thinkstock.com

Additionally, none of the recurrent biliary events occurred in those patients who did receive a cholecystectomy during the index hospitalization or within the first 30 days after discharge. “It really is the case that, ‘if you snooze, you lose,’ ” said Vijay Dalapathi, MD, presenting the findings during an oral presentation at the annual Digestive Disease Week.

Dr. Dalapathi and colleagues had observed that cholecystectomy during an index hospitalization for mild biliary pancreatitis was a far from universal practice, despite guidelines recommending early cholecystectomy.

To delve further into practice patterns, Dr. Dalapathi, first author Mohammed Ullah, MD, and their coauthors at the University of Rochester (N.Y.) conducted a single-site retrospective study of patients who were admitted with gallstone pancreatitis over a 5-year period ending December 2017. Dr. Dalapathi and Dr. Ullah are both second-year gastroenterology fellows.

The study had twin primary outcome measures: cholecystectomy rates performed during an index hospitalization for gallstone pancreatitis and recurrent biliary events after hospitalization. Adult patients were included if they had a diagnosis of acute gallstone pancreatitis, with or without recurrent cholangitis, choledocholithiasis, or acute cholecystitis. Pediatric patients and those with prior cholecystectomy were excluded.

A total of 234 patients were included in the study. Their mean age was 58.3 years, and patients were mostly female (57.3%) and white (91.5%). Mean body mass index was 29.1 kg/m². A total of 175 patients (74.8%) had endoscopic retrograde cholangiopancreatography.

Out of the entire cohort of patients, 138 (59%) did not have a cholecystectomy during the index hospitalization. Among the patients who did not receive a cholecystectomy, 33 (24%) were deemed unsuitable candidates for the procedure, either because they were critically ill or because they were poor candidates for surgery for other reasons. No reason was provided for the nonperformance of cholecystectomy for an additional 28 patients (20%).

The remaining 75 patients (54%) were deferred to outpatient management. Looking at this subgroup of patients, Dr. Dalapathi and his coinvestigators tracked the amount of time that passed before cholecystectomy.

The researchers found that 19 patients (25%) had not had a cholecystectomy within the study period. A total of 21 patients (28%) had the procedure more than 60 days from hospitalization, and another 23 (31%) had the procedure between 30 and 60 days after hospitalization. Just 12 patients (16%) of this subgroup had their cholecystectomy within 30 days of hospitalization.

Among patients who were discharged without a cholecystectomy, Dr. Dalapathi and his coauthors found 26 recurrent biliary events (19%): 15 were gallstone pancreatitis and 10 were cholecystitis; 1 patient developed cholangitis.

The crux of the study’s findings came when the investigators looked at the association between recurrent events and cholecystectomy timing. They found no recurrent biliary events among those who received cholecystectomy while hospitalized or within the first 30 days after discharge. Of the 26 events, 3 (12%) occurred in those whose cholecystectomies came 30-60 days after discharge. The remaining 23 events (88%) were seen in those receiving a cholecystectomy more than 60 days after discharge, or not at all.

Guidelines from the American Gastroenterological Association, the Society of American Gastrointestinal and Endoscopic Surgeons, and the American College of Gastroenterology all recommend early cholecystectomy after mild acute gallstone pancreatitis, said Dr. Dalapathi.

However, two separate systematic reviews including a total of 22 studies and over 3,000 patients showed that about half (48% and 51%) of patients admitted with mild acute biliary pancreatitis received a cholecystectomy during the index hospitalization or within 14 days of the hospitalization.

Further, he said, previous work had shown recurrent biliary event rates approaching 20% for patients whose biliary pancreatitis bout was not followed by cholecystectomy, a figure in line with the rate seen in the present study.

“Cholecystectomy should be performed during index hospitalization or as soon as possible within 30 days of mild biliary pancreatitis to minimize risk of recurrent biliary events,” said Dr. Dalapathi.

The authors reported no outside sources of funding and no conflicts of interest.

koakes@mdedge.com

SOURCE: Ullah M. et al. DDW 2019, Abstract 24.

SAN DIEGO – Waiting to perform cholecystectomy after mild biliary pancreatitis was associated with an increased risk of recurrent biliary events in a recent study. In a retrospective study of 234 patients admitted for gallstone pancreatitis, almost 90% of recurrent biliary events occurred in patients who did not receive a cholecystectomy within 60 days of hospital discharge. The overall rate of recurrence was 19%, and over half of patients (59%) did not receive a cholecystectomy during their index hospitalization.

Dmitrii Kotin/Thinkstock.com

Additionally, none of the recurrent biliary events occurred in those patients who did receive a cholecystectomy during the index hospitalization or within the first 30 days after discharge. “It really is the case that, ‘if you snooze, you lose,’ ” said Vijay Dalapathi, MD, presenting the findings during an oral presentation at the annual Digestive Disease Week.

Dr. Dalapathi and colleagues had observed that cholecystectomy during an index hospitalization for mild biliary pancreatitis was a far from universal practice, despite guidelines recommending early cholecystectomy.

To delve further into practice patterns, Dr. Dalapathi, first author Mohammed Ullah, MD, and their coauthors at the University of Rochester (N.Y.) conducted a single-site retrospective study of patients who were admitted with gallstone pancreatitis over a 5-year period ending December 2017. Dr. Dalapathi and Dr. Ullah are both second-year gastroenterology fellows.

The study had twin primary outcome measures: cholecystectomy rates performed during an index hospitalization for gallstone pancreatitis and recurrent biliary events after hospitalization. Adult patients were included if they had a diagnosis of acute gallstone pancreatitis, with or without recurrent cholangitis, choledocholithiasis, or acute cholecystitis. Pediatric patients and those with prior cholecystectomy were excluded.

A total of 234 patients were included in the study. Their mean age was 58.3 years, and patients were mostly female (57.3%) and white (91.5%). Mean body mass index was 29.1 kg/m². A total of 175 patients (74.8%) had endoscopic retrograde cholangiopancreatography.

Out of the entire cohort of patients, 138 (59%) did not have a cholecystectomy during the index hospitalization. Among the patients who did not receive a cholecystectomy, 33 (24%) were deemed unsuitable candidates for the procedure, either because they were critically ill or because they were poor candidates for surgery for other reasons. No reason was provided for the nonperformance of cholecystectomy for an additional 28 patients (20%).

The remaining 75 patients (54%) were deferred to outpatient management. Looking at this subgroup of patients, Dr. Dalapathi and his coinvestigators tracked the amount of time that passed before cholecystectomy.

The researchers found that 19 patients (25%) had not had a cholecystectomy within the study period. A total of 21 patients (28%) had the procedure more than 60 days from hospitalization, and another 23 (31%) had the procedure between 30 and 60 days after hospitalization. Just 12 patients (16%) of this subgroup had their cholecystectomy within 30 days of hospitalization.

Among patients who were discharged without a cholecystectomy, Dr. Dalapathi and his coauthors found 26 recurrent biliary events (19%): 15 were gallstone pancreatitis and 10 were cholecystitis; 1 patient developed cholangitis.

The crux of the study’s findings came when the investigators looked at the association between recurrent events and cholecystectomy timing. They found no recurrent biliary events among those who received cholecystectomy while hospitalized or within the first 30 days after discharge. Of the 26 events, 3 (12%) occurred in those whose cholecystectomies came 30-60 days after discharge. The remaining 23 events (88%) were seen in those receiving a cholecystectomy more than 60 days after discharge, or not at all.

Guidelines from the American Gastroenterological Association, the Society of American Gastrointestinal and Endoscopic Surgeons, and the American College of Gastroenterology all recommend early cholecystectomy after mild acute gallstone pancreatitis, said Dr. Dalapathi.

However, two separate systematic reviews including a total of 22 studies and over 3,000 patients showed that about half (48% and 51%) of patients admitted with mild acute biliary pancreatitis received a cholecystectomy during the index hospitalization or within 14 days of the hospitalization.

Further, he said, previous work had shown recurrent biliary event rates approaching 20% for patients whose biliary pancreatitis bout was not followed by cholecystectomy, a figure in line with the rate seen in the present study.

“Cholecystectomy should be performed during index hospitalization or as soon as possible within 30 days of mild biliary pancreatitis to minimize risk of recurrent biliary events,” said Dr. Dalapathi.

The authors reported no outside sources of funding and no conflicts of interest.

koakes@mdedge.com

SOURCE: Ullah M. et al. DDW 2019, Abstract 24.

Debate exists regarding the optimal method of evaluation of the urinary tract at the time of hysterectomy and the circumstances under which it should be performed. Procedures directed at prolapse and incontinence have rates of genitourinary injury as high as 11%-38%, and national guidelines affirm the importance of cystoscopy in these patients.¹ However, for patients undergoing hysterectomy in the absence of these procedures, the optimal strategy is debated. One approach that has been advanced is a policy of universal cystoscopy at the time of hysterectomy. This policy, by which all women undergoing hysterectomy would undergo cystoscopy, aims to prevent the occurrence of an unrecognized genitourinary injury by diagnosing and treating the injury intraoperatively. However, cystoscopy is not the only method that can be used to evaluate the urinary tract. Retroperitoneal dissection also can be used to visually identify the pertinent structures and has been performed with high fidelity by generations of experienced and skilled pelvic surgeons.

Injuries that are not identified intraoperatively at the time of surgery, so-called delayed genitourinary tract injuries, are associated with serious postoperative consequences for patients and high costs for institutions. As surgeons strive to decrease complications and improve the quality of gynecologic surgery, the question of whether cystoscopy should routinely be performed at the time of hysterectomy for benign indications remains unanswered. Proponents argue that cystoscopy is a low-cost assessment and that 75% of genitourinary injuries occur in women without identifiable risk factors.² Opponents point out that cystoscopy is not an entirely benign intervention; it is associated with increased rates of urinary tract infection, bladder and ureteral trauma, and additional operating room time. Furthermore, it is unclear that the use of cystoscopy will reduce the incidence of delayed genitourinary tract injury in clinical practice.

Ultimately, cystoscopy after hysterectomy is being used as a screening test for genitourinary injury, and this lens can be applied to provide more information about its usefulness. For screening tests, the sensitivity and false negative rate are of paramount importance. High sensitivity and resultant few false negatives are the characteristics of a robust screening test which has a low likelihood of missing a diagnosis. Unfortunately, the sensitivity of cystoscopy is not 100% for genitourinary tract injury; it ranges from 60% to 85% and can be as low as 43% for ureteral injury.^3,4 This means that cystoscopy will falsely reassure the surgeon with normal results in greater than 50% of the cases in which the patient actually has a ureteral injury.

Some larger series call into question the usefulness of cystoscopy as a screening tool, finding that this evaluation is not associated with a decreased rate of delayed genitourinary injury. A recent publication by our group of a series of 39,529 women who underwent benign hysterectomy without procedures directed at incontinence and prolapse recorded in the National Surgical Quality Improvement Program (NSQIP) database between 2015 and 2017 found no difference in the rate of delayed genitourinary injury among women exposed to diagnostic cystoscopy and those who were not.⁵ These results are consistent with those of the largest systematic review and meta-analysis of 79 studies capturing 41,482 hysterectomies which found universal cystoscopy was not associated with a decreased rate of delayed genitourinary tract injury.⁶

Another consideration with the use of universal cystoscopy is cost. Although cystoscopy is typically a short procedure, the false positive rate is approximately 2%,² often leading to additional interventions to evaluate the urinary tract which can be time consuming. In the limited available data regarding operative time, patients who underwent cystoscopy had a median operative time that was 17 minutes longer than it was among patients who did not.⁵ Moreover, there may be risks associated with this additional bladder instrumentation, evidenced by an increased incidence of urinary tract infection among women undergoing cystoscopy. In a recent cost-effectiveness analysis of cystoscopy at the time of benign hysterectomy, universal cystoscopy was found to add $51.39-$57.86 per case, and the risk of bladder injury would need to exceed 21%-47% and ureteral injury 27%-38% to be cost saving, compared with selective cystoscopy.⁷ A prior cost-effectiveness analysis concluded that universal cystoscopy is cost effective when the incidence of ureteral injury at the time of hysterectomy exceeds 1.5%-2.0%.⁸ Given these high thresholds, with a contemporary composite lower–genitourinary tract injury incidence of 0.24%-0.27%, it is unlikely that universal cystoscopy could be considered a cost-saving strategy in the majority of clinical settings.

Potential explanations for these results are many. Intraoperative cystoscopy is likely to be normal in the setting of nonobstructive and thermal injuries, which in the current era of minimally invasive surgery may be more prevalent mechanisms of injury. False positives can occur leading to unnecessary interventions, as well as overdiagnosis of asymptomatic urinary tract injuries that may have resolved spontaneously.⁹ It has been observed that cystoscopy is performed less frequently when hysterectomy is completed by a high-volume surgeon, which suggests that surgeon skill and experience play a significant role in the usefulness of this evaluation.⁹

Given these data, what is the best way forward regarding evaluation of the urinary tract at the time of benign hysterectomy? Ultimately, this is a clinical question that should be individualized, taking into account patient and surgical complexity, as well as surgeon training and individual rates of genitourinary injuries.⁹ Given its low sensitivity, caution should be exercised regarding the routine use of cystoscopy alone for evaluation of the urinary tract because false negatives occur with significant frequency. Benefits of cystoscopy in a given clinical scenario should be weighed against the risks of longer operative time, increased costs, and increased rate of urinary tract infection. In the absence of clinical scenarios with high rates of genitourinary injury (greater than 5%), selective rather than universal cystoscopy is the preferred strategy.⁷ Cystoscopy is fundamentally a form of secondary prevention that aims to mitigate damage that has already been done, and is no substitute for primary prevention of genitourinary tract injury itself through thorough knowledge of pelvic anatomy, comfort with retroperitoneal dissection, and awareness of the ureter and bladder at all times.

Dr. Polan is a resident in obstetrics and gynecology at Northwestern University, Chicago. Dr. Barber is an assistant professor of obstetrics and gynecology, specializing in gynecologic oncology, at the university. Neither of them have relevant financial disclosures. Email Dr. Polan and Dr. Barber at obnews@mdedge.com.

References

1. Am J Obstet Gynecol. 2018 Jul;219(1):75-7.

2. Obstet Gynecol. 2009 Jan;113(1):6-10.

3. Obstet Gynecol. 2016 Feb;127(2):369-75.

4. J Minim Invasive Gynecol. 2015 Nov-Dec;22(7):1278-86.

5. Obstet Gynecol. 2019 May;133(5):888-95.

6. Obstet Gynecol. 2015 Dec;126(6):1161-9.

7. Am J Obstet Gynecol. 2019 Apr;220(4):369.e1-7.

8. Obstet Gynecol. 2001 May;97(5 Pt 1):685-92.

9. Obstet Gynecol. 2012 Dec;120(6):1363-70.

Debate exists regarding the optimal method of evaluation of the urinary tract at the time of hysterectomy and the circumstances under which it should be performed. Procedures directed at prolapse and incontinence have rates of genitourinary injury as high as 11%-38%, and national guidelines affirm the importance of cystoscopy in these patients.¹ However, for patients undergoing hysterectomy in the absence of these procedures, the optimal strategy is debated. One approach that has been advanced is a policy of universal cystoscopy at the time of hysterectomy. This policy, by which all women undergoing hysterectomy would undergo cystoscopy, aims to prevent the occurrence of an unrecognized genitourinary injury by diagnosing and treating the injury intraoperatively. However, cystoscopy is not the only method that can be used to evaluate the urinary tract. Retroperitoneal dissection also can be used to visually identify the pertinent structures and has been performed with high fidelity by generations of experienced and skilled pelvic surgeons.

Injuries that are not identified intraoperatively at the time of surgery, so-called delayed genitourinary tract injuries, are associated with serious postoperative consequences for patients and high costs for institutions. As surgeons strive to decrease complications and improve the quality of gynecologic surgery, the question of whether cystoscopy should routinely be performed at the time of hysterectomy for benign indications remains unanswered. Proponents argue that cystoscopy is a low-cost assessment and that 75% of genitourinary injuries occur in women without identifiable risk factors.² Opponents point out that cystoscopy is not an entirely benign intervention; it is associated with increased rates of urinary tract infection, bladder and ureteral trauma, and additional operating room time. Furthermore, it is unclear that the use of cystoscopy will reduce the incidence of delayed genitourinary tract injury in clinical practice.

Ultimately, cystoscopy after hysterectomy is being used as a screening test for genitourinary injury, and this lens can be applied to provide more information about its usefulness. For screening tests, the sensitivity and false negative rate are of paramount importance. High sensitivity and resultant few false negatives are the characteristics of a robust screening test which has a low likelihood of missing a diagnosis. Unfortunately, the sensitivity of cystoscopy is not 100% for genitourinary tract injury; it ranges from 60% to 85% and can be as low as 43% for ureteral injury.^3,4 This means that cystoscopy will falsely reassure the surgeon with normal results in greater than 50% of the cases in which the patient actually has a ureteral injury.

Some larger series call into question the usefulness of cystoscopy as a screening tool, finding that this evaluation is not associated with a decreased rate of delayed genitourinary injury. A recent publication by our group of a series of 39,529 women who underwent benign hysterectomy without procedures directed at incontinence and prolapse recorded in the National Surgical Quality Improvement Program (NSQIP) database between 2015 and 2017 found no difference in the rate of delayed genitourinary injury among women exposed to diagnostic cystoscopy and those who were not.⁵ These results are consistent with those of the largest systematic review and meta-analysis of 79 studies capturing 41,482 hysterectomies which found universal cystoscopy was not associated with a decreased rate of delayed genitourinary tract injury.⁶

Another consideration with the use of universal cystoscopy is cost. Although cystoscopy is typically a short procedure, the false positive rate is approximately 2%,² often leading to additional interventions to evaluate the urinary tract which can be time consuming. In the limited available data regarding operative time, patients who underwent cystoscopy had a median operative time that was 17 minutes longer than it was among patients who did not.⁵ Moreover, there may be risks associated with this additional bladder instrumentation, evidenced by an increased incidence of urinary tract infection among women undergoing cystoscopy. In a recent cost-effectiveness analysis of cystoscopy at the time of benign hysterectomy, universal cystoscopy was found to add $51.39-$57.86 per case, and the risk of bladder injury would need to exceed 21%-47% and ureteral injury 27%-38% to be cost saving, compared with selective cystoscopy.⁷ A prior cost-effectiveness analysis concluded that universal cystoscopy is cost effective when the incidence of ureteral injury at the time of hysterectomy exceeds 1.5%-2.0%.⁸ Given these high thresholds, with a contemporary composite lower–genitourinary tract injury incidence of 0.24%-0.27%, it is unlikely that universal cystoscopy could be considered a cost-saving strategy in the majority of clinical settings.

Potential explanations for these results are many. Intraoperative cystoscopy is likely to be normal in the setting of nonobstructive and thermal injuries, which in the current era of minimally invasive surgery may be more prevalent mechanisms of injury. False positives can occur leading to unnecessary interventions, as well as overdiagnosis of asymptomatic urinary tract injuries that may have resolved spontaneously.⁹ It has been observed that cystoscopy is performed less frequently when hysterectomy is completed by a high-volume surgeon, which suggests that surgeon skill and experience play a significant role in the usefulness of this evaluation.⁹

Given these data, what is the best way forward regarding evaluation of the urinary tract at the time of benign hysterectomy? Ultimately, this is a clinical question that should be individualized, taking into account patient and surgical complexity, as well as surgeon training and individual rates of genitourinary injuries.⁹ Given its low sensitivity, caution should be exercised regarding the routine use of cystoscopy alone for evaluation of the urinary tract because false negatives occur with significant frequency. Benefits of cystoscopy in a given clinical scenario should be weighed against the risks of longer operative time, increased costs, and increased rate of urinary tract infection. In the absence of clinical scenarios with high rates of genitourinary injury (greater than 5%), selective rather than universal cystoscopy is the preferred strategy.⁷ Cystoscopy is fundamentally a form of secondary prevention that aims to mitigate damage that has already been done, and is no substitute for primary prevention of genitourinary tract injury itself through thorough knowledge of pelvic anatomy, comfort with retroperitoneal dissection, and awareness of the ureter and bladder at all times.

Dr. Polan is a resident in obstetrics and gynecology at Northwestern University, Chicago. Dr. Barber is an assistant professor of obstetrics and gynecology, specializing in gynecologic oncology, at the university. Neither of them have relevant financial disclosures. Email Dr. Polan and Dr. Barber at obnews@mdedge.com.

References

1. Am J Obstet Gynecol. 2018 Jul;219(1):75-7.

2. Obstet Gynecol. 2009 Jan;113(1):6-10.

3. Obstet Gynecol. 2016 Feb;127(2):369-75.

4. J Minim Invasive Gynecol. 2015 Nov-Dec;22(7):1278-86.

5. Obstet Gynecol. 2019 May;133(5):888-95.

6. Obstet Gynecol. 2015 Dec;126(6):1161-9.

7. Am J Obstet Gynecol. 2019 Apr;220(4):369.e1-7.

8. Obstet Gynecol. 2001 May;97(5 Pt 1):685-92.

9. Obstet Gynecol. 2012 Dec;120(6):1363-70.

Debate exists regarding the optimal method of evaluation of the urinary tract at the time of hysterectomy and the circumstances under which it should be performed. Procedures directed at prolapse and incontinence have rates of genitourinary injury as high as 11%-38%, and national guidelines affirm the importance of cystoscopy in these patients.¹ However, for patients undergoing hysterectomy in the absence of these procedures, the optimal strategy is debated. One approach that has been advanced is a policy of universal cystoscopy at the time of hysterectomy. This policy, by which all women undergoing hysterectomy would undergo cystoscopy, aims to prevent the occurrence of an unrecognized genitourinary injury by diagnosing and treating the injury intraoperatively. However, cystoscopy is not the only method that can be used to evaluate the urinary tract. Retroperitoneal dissection also can be used to visually identify the pertinent structures and has been performed with high fidelity by generations of experienced and skilled pelvic surgeons.

Injuries that are not identified intraoperatively at the time of surgery, so-called delayed genitourinary tract injuries, are associated with serious postoperative consequences for patients and high costs for institutions. As surgeons strive to decrease complications and improve the quality of gynecologic surgery, the question of whether cystoscopy should routinely be performed at the time of hysterectomy for benign indications remains unanswered. Proponents argue that cystoscopy is a low-cost assessment and that 75% of genitourinary injuries occur in women without identifiable risk factors.² Opponents point out that cystoscopy is not an entirely benign intervention; it is associated with increased rates of urinary tract infection, bladder and ureteral trauma, and additional operating room time. Furthermore, it is unclear that the use of cystoscopy will reduce the incidence of delayed genitourinary tract injury in clinical practice.

Ultimately, cystoscopy after hysterectomy is being used as a screening test for genitourinary injury, and this lens can be applied to provide more information about its usefulness. For screening tests, the sensitivity and false negative rate are of paramount importance. High sensitivity and resultant few false negatives are the characteristics of a robust screening test which has a low likelihood of missing a diagnosis. Unfortunately, the sensitivity of cystoscopy is not 100% for genitourinary tract injury; it ranges from 60% to 85% and can be as low as 43% for ureteral injury.^3,4 This means that cystoscopy will falsely reassure the surgeon with normal results in greater than 50% of the cases in which the patient actually has a ureteral injury.

Some larger series call into question the usefulness of cystoscopy as a screening tool, finding that this evaluation is not associated with a decreased rate of delayed genitourinary injury. A recent publication by our group of a series of 39,529 women who underwent benign hysterectomy without procedures directed at incontinence and prolapse recorded in the National Surgical Quality Improvement Program (NSQIP) database between 2015 and 2017 found no difference in the rate of delayed genitourinary injury among women exposed to diagnostic cystoscopy and those who were not.⁵ These results are consistent with those of the largest systematic review and meta-analysis of 79 studies capturing 41,482 hysterectomies which found universal cystoscopy was not associated with a decreased rate of delayed genitourinary tract injury.⁶

Another consideration with the use of universal cystoscopy is cost. Although cystoscopy is typically a short procedure, the false positive rate is approximately 2%,² often leading to additional interventions to evaluate the urinary tract which can be time consuming. In the limited available data regarding operative time, patients who underwent cystoscopy had a median operative time that was 17 minutes longer than it was among patients who did not.⁵ Moreover, there may be risks associated with this additional bladder instrumentation, evidenced by an increased incidence of urinary tract infection among women undergoing cystoscopy. In a recent cost-effectiveness analysis of cystoscopy at the time of benign hysterectomy, universal cystoscopy was found to add $51.39-$57.86 per case, and the risk of bladder injury would need to exceed 21%-47% and ureteral injury 27%-38% to be cost saving, compared with selective cystoscopy.⁷ A prior cost-effectiveness analysis concluded that universal cystoscopy is cost effective when the incidence of ureteral injury at the time of hysterectomy exceeds 1.5%-2.0%.⁸ Given these high thresholds, with a contemporary composite lower–genitourinary tract injury incidence of 0.24%-0.27%, it is unlikely that universal cystoscopy could be considered a cost-saving strategy in the majority of clinical settings.

Potential explanations for these results are many. Intraoperative cystoscopy is likely to be normal in the setting of nonobstructive and thermal injuries, which in the current era of minimally invasive surgery may be more prevalent mechanisms of injury. False positives can occur leading to unnecessary interventions, as well as overdiagnosis of asymptomatic urinary tract injuries that may have resolved spontaneously.⁹ It has been observed that cystoscopy is performed less frequently when hysterectomy is completed by a high-volume surgeon, which suggests that surgeon skill and experience play a significant role in the usefulness of this evaluation.⁹

Given these data, what is the best way forward regarding evaluation of the urinary tract at the time of benign hysterectomy? Ultimately, this is a clinical question that should be individualized, taking into account patient and surgical complexity, as well as surgeon training and individual rates of genitourinary injuries.⁹ Given its low sensitivity, caution should be exercised regarding the routine use of cystoscopy alone for evaluation of the urinary tract because false negatives occur with significant frequency. Benefits of cystoscopy in a given clinical scenario should be weighed against the risks of longer operative time, increased costs, and increased rate of urinary tract infection. In the absence of clinical scenarios with high rates of genitourinary injury (greater than 5%), selective rather than universal cystoscopy is the preferred strategy.⁷ Cystoscopy is fundamentally a form of secondary prevention that aims to mitigate damage that has already been done, and is no substitute for primary prevention of genitourinary tract injury itself through thorough knowledge of pelvic anatomy, comfort with retroperitoneal dissection, and awareness of the ureter and bladder at all times.

Dr. Polan is a resident in obstetrics and gynecology at Northwestern University, Chicago. Dr. Barber is an assistant professor of obstetrics and gynecology, specializing in gynecologic oncology, at the university. Neither of them have relevant financial disclosures. Email Dr. Polan and Dr. Barber at obnews@mdedge.com.

References

1. Am J Obstet Gynecol. 2018 Jul;219(1):75-7.

2. Obstet Gynecol. 2009 Jan;113(1):6-10.

3. Obstet Gynecol. 2016 Feb;127(2):369-75.

4. J Minim Invasive Gynecol. 2015 Nov-Dec;22(7):1278-86.

5. Obstet Gynecol. 2019 May;133(5):888-95.

6. Obstet Gynecol. 2015 Dec;126(6):1161-9.

7. Am J Obstet Gynecol. 2019 Apr;220(4):369.e1-7.

8. Obstet Gynecol. 2001 May;97(5 Pt 1):685-92.

9. Obstet Gynecol. 2012 Dec;120(6):1363-70.

Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.

Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.

Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.

“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.

“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”

With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.

The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).

In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m² (n = 3), 400 mg/m² (n = 3), 550 mg/m² (n = 7), or 750 mg/m² (n = 3).

In the phase 1b portion, patients received entrectinib at 550 mg/m² (n = 7) – the recommended dose – or 400 mg/m² (n = 6) if they were unable to swallow intact capsules.

Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.

“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”

In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.

Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.

Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).

“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”

Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.

The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.

jensmith@mdedge.com

SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.

Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.

Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.

Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.

“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.

“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”

With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.

The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).

In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m² (n = 3), 400 mg/m² (n = 3), 550 mg/m² (n = 7), or 750 mg/m² (n = 3).

In the phase 1b portion, patients received entrectinib at 550 mg/m² (n = 7) – the recommended dose – or 400 mg/m² (n = 6) if they were unable to swallow intact capsules.

Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.

“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”

In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.

Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.

Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).

“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”

Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.

The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.

jensmith@mdedge.com

SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.

Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.

Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.

Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.

“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.

“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”

With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.

The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).

In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m² (n = 3), 400 mg/m² (n = 3), 550 mg/m² (n = 7), or 750 mg/m² (n = 3).

In the phase 1b portion, patients received entrectinib at 550 mg/m² (n = 7) – the recommended dose – or 400 mg/m² (n = 6) if they were unable to swallow intact capsules.

Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.

“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”

In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.

Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.

Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).

“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”

Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.

The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.

jensmith@mdedge.com

SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.