Key clinical point: The Polygenic Hazard Score (PHS2) was effective for risk-stratifying men for prostate cancer in a large, multiethnic data set.

Major finding: The Polygenic Hazard Score (PHS2) indicated hazard ratios for prostate cancer, aggressive cancer, and prostate cancer-specific death of 5.32, 5.88, and 5.68, respectively, when researchers compared the 80^th and 20^th PHS2 percentiles.

Study details: The data come from 80,491 men enrolled in the OncoArray genetic project; researchers tested the polygenic hazard score (PHS2, adapted for OncoArray) for association with age at diagnosis of any and aggressive prostate cancer.

Disclosures: The study was supported in part by the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering, the United States Department of Defense, the University of California, the Research Council of Norway, K.G. Jebsen Stiftelsen, and South East Norway Health Authority. Lead author Dr. Huynh-Le had no financial conflicts to disclose.

Source: Huynh-Le M-P et al. Nat Commun. 2021 Feb 23. doi: 10.1038/s41467-021-21287-0.

Key clinical point: The Polygenic Hazard Score (PHS2) was effective for risk-stratifying men for prostate cancer in a large, multiethnic data set.

Major finding: The Polygenic Hazard Score (PHS2) indicated hazard ratios for prostate cancer, aggressive cancer, and prostate cancer-specific death of 5.32, 5.88, and 5.68, respectively, when researchers compared the 80^th and 20^th PHS2 percentiles.

Study details: The data come from 80,491 men enrolled in the OncoArray genetic project; researchers tested the polygenic hazard score (PHS2, adapted for OncoArray) for association with age at diagnosis of any and aggressive prostate cancer.

Disclosures: The study was supported in part by the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering, the United States Department of Defense, the University of California, the Research Council of Norway, K.G. Jebsen Stiftelsen, and South East Norway Health Authority. Lead author Dr. Huynh-Le had no financial conflicts to disclose.

Source: Huynh-Le M-P et al. Nat Commun. 2021 Feb 23. doi: 10.1038/s41467-021-21287-0.

Key clinical point: The Polygenic Hazard Score (PHS2) was effective for risk-stratifying men for prostate cancer in a large, multiethnic data set.

Major finding: The Polygenic Hazard Score (PHS2) indicated hazard ratios for prostate cancer, aggressive cancer, and prostate cancer-specific death of 5.32, 5.88, and 5.68, respectively, when researchers compared the 80^th and 20^th PHS2 percentiles.

Study details: The data come from 80,491 men enrolled in the OncoArray genetic project; researchers tested the polygenic hazard score (PHS2, adapted for OncoArray) for association with age at diagnosis of any and aggressive prostate cancer.

Disclosures: The study was supported in part by the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering, the United States Department of Defense, the University of California, the Research Council of Norway, K.G. Jebsen Stiftelsen, and South East Norway Health Authority. Lead author Dr. Huynh-Le had no financial conflicts to disclose.

Source: Huynh-Le M-P et al. Nat Commun. 2021 Feb 23. doi: 10.1038/s41467-021-21287-0.

Key clinical point: Increased use of PSA testing and diagnostic activity increased the number of men diagnosed with low and intermediate-risk prostate cancer.

Major finding: The number of men diagnosed with prostate cancer increased by 48% in the high diagnostic activity model compared to the low diagnostic activity model (423 cases per 100,000 me per year vs. 286 cases per 100,000 men per year). 

Study details: The data come from a cohort study of 188,884 men aged 64-77 years diagnosed with prostate cancer between 1996 and 2016 in Sweden. The researchers used a simulation model to compare scenarios of high and low diagnostic activity for prostate cancer.

Disclosures: The study was funded by the Swedish Cancer Society. The researchers had no financial conflicts to disclose.

Source: Bergengren O et al. JAMA Netw Open. 2021 May 17. doi: 10.1001/jamanetworkopen.2021.9444.

Key clinical point: Increased use of PSA testing and diagnostic activity increased the number of men diagnosed with low and intermediate-risk prostate cancer.

Major finding: The number of men diagnosed with prostate cancer increased by 48% in the high diagnostic activity model compared to the low diagnostic activity model (423 cases per 100,000 me per year vs. 286 cases per 100,000 men per year). 

Study details: The data come from a cohort study of 188,884 men aged 64-77 years diagnosed with prostate cancer between 1996 and 2016 in Sweden. The researchers used a simulation model to compare scenarios of high and low diagnostic activity for prostate cancer.

Disclosures: The study was funded by the Swedish Cancer Society. The researchers had no financial conflicts to disclose.

Source: Bergengren O et al. JAMA Netw Open. 2021 May 17. doi: 10.1001/jamanetworkopen.2021.9444.

Key clinical point: Increased use of PSA testing and diagnostic activity increased the number of men diagnosed with low and intermediate-risk prostate cancer.

Major finding: The number of men diagnosed with prostate cancer increased by 48% in the high diagnostic activity model compared to the low diagnostic activity model (423 cases per 100,000 me per year vs. 286 cases per 100,000 men per year). 

Study details: The data come from a cohort study of 188,884 men aged 64-77 years diagnosed with prostate cancer between 1996 and 2016 in Sweden. The researchers used a simulation model to compare scenarios of high and low diagnostic activity for prostate cancer.

Disclosures: The study was funded by the Swedish Cancer Society. The researchers had no financial conflicts to disclose.

Source: Bergengren O et al. JAMA Netw Open. 2021 May 17. doi: 10.1001/jamanetworkopen.2021.9444.

Key clinical point: Treatment with lutetium prostate-specific membrane antigen (Lu-PSMA) therapy at 6.0 GBq and 7.4 GBq yielded similar PSA response rates and overall survival for patients with progressive metastatic castrate resistant prostate cancer.

Major finding: The primary endpoint of PSA response of at least a 50% reduction from baseline after 2 treatment cycles was met in 28% of the whole cohort, and 46% and 19%, respectively, for treatment regimens of 6.0 GBq and 7.4 GBq.

Study details: The data come from a prospective, phase II trial of 71 men with progressive, metastatic castrate resistant prostate cancer. The patients were randomized to Lu-PSMA therapy at doses of either 6.0 vs 7.4 GBq.

Disclosures: The original study was supported by Endocyte. The researchers had no financial conflicts to disclose.  

Source: Calais J. et al. J Nucl Med. 2021 May 20. doi: 10.2967/jnumed.121.261982.

Key clinical point: Treatment with lutetium prostate-specific membrane antigen (Lu-PSMA) therapy at 6.0 GBq and 7.4 GBq yielded similar PSA response rates and overall survival for patients with progressive metastatic castrate resistant prostate cancer.

Major finding: The primary endpoint of PSA response of at least a 50% reduction from baseline after 2 treatment cycles was met in 28% of the whole cohort, and 46% and 19%, respectively, for treatment regimens of 6.0 GBq and 7.4 GBq.

Study details: The data come from a prospective, phase II trial of 71 men with progressive, metastatic castrate resistant prostate cancer. The patients were randomized to Lu-PSMA therapy at doses of either 6.0 vs 7.4 GBq.

Disclosures: The original study was supported by Endocyte. The researchers had no financial conflicts to disclose.  

Source: Calais J. et al. J Nucl Med. 2021 May 20. doi: 10.2967/jnumed.121.261982.

Key clinical point: Treatment with lutetium prostate-specific membrane antigen (Lu-PSMA) therapy at 6.0 GBq and 7.4 GBq yielded similar PSA response rates and overall survival for patients with progressive metastatic castrate resistant prostate cancer.

Major finding: The primary endpoint of PSA response of at least a 50% reduction from baseline after 2 treatment cycles was met in 28% of the whole cohort, and 46% and 19%, respectively, for treatment regimens of 6.0 GBq and 7.4 GBq.

Study details: The data come from a prospective, phase II trial of 71 men with progressive, metastatic castrate resistant prostate cancer. The patients were randomized to Lu-PSMA therapy at doses of either 6.0 vs 7.4 GBq.

Disclosures: The original study was supported by Endocyte. The researchers had no financial conflicts to disclose.  

Source: Calais J. et al. J Nucl Med. 2021 May 20. doi: 10.2967/jnumed.121.261982.

Key clinical point: A serum metabolic panel was more effective than prostate-specific antigen at differentiating prostate cancer patients from patients with negative prostate biopsy and healthy controls.

Major finding: The metabolic panel showed a higher diagnostic performance than prostate-specific antigen in distinguishing PCa from control patients, with an area under the curve of 0.823 for the metabolic panel vs. 0.712 for PSA (P <0.001).

Study details: The data come from a logistic regression analysis of 134 individuals, 39 prostate cancer patients, 45 controls with a negative prostate biopsy, and 50 healthy controls.

Disclosures: The study was funded by the National Natural Science Foundation of China, Science and Technology Support Project in the field of biomedicine of Shanghai Science and Technology Action Plan, Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning, Precision Medicine Program of Second Military Medical University, Youth Startup Program of Second Military Medical University, and Jiangsu Provincial Medical Youth Talent. The researchers had no financial conflicts to disclose.

Source: Xu H et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.666320.

Key clinical point: A serum metabolic panel was more effective than prostate-specific antigen at differentiating prostate cancer patients from patients with negative prostate biopsy and healthy controls.

Major finding: The metabolic panel showed a higher diagnostic performance than prostate-specific antigen in distinguishing PCa from control patients, with an area under the curve of 0.823 for the metabolic panel vs. 0.712 for PSA (P <0.001).

Study details: The data come from a logistic regression analysis of 134 individuals, 39 prostate cancer patients, 45 controls with a negative prostate biopsy, and 50 healthy controls.

Disclosures: The study was funded by the National Natural Science Foundation of China, Science and Technology Support Project in the field of biomedicine of Shanghai Science and Technology Action Plan, Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning, Precision Medicine Program of Second Military Medical University, Youth Startup Program of Second Military Medical University, and Jiangsu Provincial Medical Youth Talent. The researchers had no financial conflicts to disclose.

Source: Xu H et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.666320.

Key clinical point: A serum metabolic panel was more effective than prostate-specific antigen at differentiating prostate cancer patients from patients with negative prostate biopsy and healthy controls.

Major finding: The metabolic panel showed a higher diagnostic performance than prostate-specific antigen in distinguishing PCa from control patients, with an area under the curve of 0.823 for the metabolic panel vs. 0.712 for PSA (P <0.001).

Study details: The data come from a logistic regression analysis of 134 individuals, 39 prostate cancer patients, 45 controls with a negative prostate biopsy, and 50 healthy controls.

Disclosures: The study was funded by the National Natural Science Foundation of China, Science and Technology Support Project in the field of biomedicine of Shanghai Science and Technology Action Plan, Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning, Precision Medicine Program of Second Military Medical University, Youth Startup Program of Second Military Medical University, and Jiangsu Provincial Medical Youth Talent. The researchers had no financial conflicts to disclose.

Source: Xu H et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.666320.

Key clinical point: Overall survival among men with castration sensitive prostate cancer was similar whether they were treated with docetaxel or abiraterone, but progression-free survival favored abiraterone patients.

Major finding: Progression-free survival at 12 months was greater among men who received ABI compared to those who received DOC (79.7% vs. 67.1%). Overall survival rates at 12 months were similar between the ABI and DOC groups (92.7% and 98.7%, respectively).

Study details: The data come from a retrospective analysis of 121 men with castration sensitive prostate cancer (mCSPC) who were treated at a single center between December 2014 and March 2021; 79 received docetaxel and 42 received abiraterone in addition to androgen deprivation therapy.

Disclosures: The study was supported by the Joseph and Silvana Melara Cancer Research Fund. Lead author Dr. Briones had no financial conflicts to disclose.

Source: Briones J et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.658331.

Key clinical point: Overall survival among men with castration sensitive prostate cancer was similar whether they were treated with docetaxel or abiraterone, but progression-free survival favored abiraterone patients.

Major finding: Progression-free survival at 12 months was greater among men who received ABI compared to those who received DOC (79.7% vs. 67.1%). Overall survival rates at 12 months were similar between the ABI and DOC groups (92.7% and 98.7%, respectively).

Study details: The data come from a retrospective analysis of 121 men with castration sensitive prostate cancer (mCSPC) who were treated at a single center between December 2014 and March 2021; 79 received docetaxel and 42 received abiraterone in addition to androgen deprivation therapy.

Disclosures: The study was supported by the Joseph and Silvana Melara Cancer Research Fund. Lead author Dr. Briones had no financial conflicts to disclose.

Source: Briones J et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.658331.

Key clinical point: Overall survival among men with castration sensitive prostate cancer was similar whether they were treated with docetaxel or abiraterone, but progression-free survival favored abiraterone patients.

Major finding: Progression-free survival at 12 months was greater among men who received ABI compared to those who received DOC (79.7% vs. 67.1%). Overall survival rates at 12 months were similar between the ABI and DOC groups (92.7% and 98.7%, respectively).

Study details: The data come from a retrospective analysis of 121 men with castration sensitive prostate cancer (mCSPC) who were treated at a single center between December 2014 and March 2021; 79 received docetaxel and 42 received abiraterone in addition to androgen deprivation therapy.

Disclosures: The study was supported by the Joseph and Silvana Melara Cancer Research Fund. Lead author Dr. Briones had no financial conflicts to disclose.

Source: Briones J et al. Front Oncol. 2021 May 7. doi: 10.3389/fonc.2021.658331.

With intensive care units stretched to their limits – and beyond – during the COVID-19 pandemic, hospitalists became more central than ever in orchestrating the response.

At SHM Converge, the annual conference of the Society of Hospital Medicine, two hospitalists shared how their teams helped to develop new critical care units and strategies for best managing and allocating care to COVID patients in the ICU.

“The pandemic has been a selective pressure on us as a specialty,” said Jason Stein, MD, SFHM, a full-time clinical hospitalist at Roper Hospital, a 332-bed facility in Charleston, S.C.

Dr. Stein explained how hospitalists at Roper helped create the Progressive Care Unit – a negative-pressure unit with 12 high-flow oxygen beds overseen by a hospital medicine team, with the help of a respiratory therapist, pharmacist, and nurses. Patients in this unit had escalating acuity – quickly increasing oxygen needs – or deescalating acuity, such as ICU transfers, Dr. Stein said. Cardiac catheterization space was converted for the unit, which was intended to preserve beds in the hospital ICU for patients needing mechanical ventilation or vasoactive medication.

Interdisciplinary rounds – to assess oxygen and inflammatory marker trends, and run through a COVID care checklist – took place every day at 10 a.m.

“Consistency was the key,” Dr. Stein said.

At Weill Cornell Medical Center in New York, hospitalists helped build the COVID Recovery Unit, which was dedicated to the care of patients coming out of the ICU, said Vishwas Anand Singh, MD, MS, FHM, cochief of hospital medicine at New York Presbyterian–Lower Manhattan Hospital.

“The pandemic created an unprecedented need for critical care, and post-ICU care,” Dr. Singh said. “After extubation, patients remain very complicated and they have unique needs.”

The 30-bed COVID Recovery Unit – converted from a behavioral health unit – was designed to meet those needs. It was staffed by one lead hospitalist, 3 hospitalist physicians, 3 advanced practitioners, about 12 nurses and a neurologist, psychiatrist, and neuropsychologist.

The idea was to integrate medical care with careful attention to rehab and neuropsychological needs, Dr. Singh said. To be in the unit, patients had to be medically stable but with ongoing medical and rehabilitation needs and able to tolerate about half an hour of physical or occupational therapy each day.

The space was set up so that patients could interact with each other as well as staff, and this ability to share their experiences of trauma and recovery “led to an improved sense of psychological well-being and to healing,” according to Dr. Singh. Group therapy and meditation were also held several times a week.

“All this together, we thought we were really meeting the need for a lot of these patients from medical to psychosocial,” he said.

New York Presbyterian––Lower Manhattan Hospital also established a program called ICU Outreach to give hospitalists a “bird’s eye view” of the ICU in order to help move patients from unit to unit for optimized care. One hospitalist acted as a bridge between the ICU, the floors, and the emergency room.

The hospitalist on duty touched based with the ICU each day at 10 a.m., assessed the available beds, compiled a list of patients being discharged, met with all of the hospitalists and individual teams in inpatient and emergency services, and compiled a list of “watchers” – the sickest patients who needed help being managed.

The broad perspective was important, Dr. Singh said.

“We quickly found that each individual team or provider only knew the patients they were caring for, and the ICU Outreach person knew the whole big picture and could put the pieces together,” he said. “They could answer who was next in line for a bed, who benefited from a goals of care discussion, who could be managed on the floor with assistance. And this bridge, having this person fill this role, allowed the intensivists to focus on the patients they had in the unit.”
 

Palliative care and patient flow

Dr. Singh also described how hospitalists played an important role in palliative care for COVID patients. The hospital medicine team offered hospitalist palliative care services, which included COVIDtalk, a course on communicating about end of life, which helped to expand the pool of palliative care providers. Those trained were taught that these difficult conversations had to be honest and clear, with the goals of care addressed very early in the admission, should a patient decompensate soon after arrival.

A palliative “rapid response team” included a virtual hospitalist, a palliative care nurse practitioner, and a virtual psychiatrist – a team available 24 hours a day to have longer conversations so that clinicians could better tend to their patients when the in-person palliative care service was stretched thin, or at off hours like the middle of the night.

These innovations not only helped serve patients and families better, but also gave hospitalists training and experience in palliative care.

At Roper Hospital, Dr. Stein explained how hospitalists helped improve management of COVID patient flow. Depending on the time of day and the staffing on duty, there could be considerable confusion about where patients should go after the ED, or the COVID progressive unit, or the floor.

Hospitalists helped develop hospitalwide algorithms for escalating and deescalating acuity, Dr. Stein said, providing a “shared mental model for where a patient should go.”

“There are many ways hospitalists can and did rise to meet the unique demands of COVID,” Dr. Singh said, “whether it was innovating a new unit or service or work flow or leading a multidisciplinary team to extend or support other services that may have been strained.”
 

With intensive care units stretched to their limits – and beyond – during the COVID-19 pandemic, hospitalists became more central than ever in orchestrating the response.

At SHM Converge, the annual conference of the Society of Hospital Medicine, two hospitalists shared how their teams helped to develop new critical care units and strategies for best managing and allocating care to COVID patients in the ICU.

“The pandemic has been a selective pressure on us as a specialty,” said Jason Stein, MD, SFHM, a full-time clinical hospitalist at Roper Hospital, a 332-bed facility in Charleston, S.C.

Dr. Stein explained how hospitalists at Roper helped create the Progressive Care Unit – a negative-pressure unit with 12 high-flow oxygen beds overseen by a hospital medicine team, with the help of a respiratory therapist, pharmacist, and nurses. Patients in this unit had escalating acuity – quickly increasing oxygen needs – or deescalating acuity, such as ICU transfers, Dr. Stein said. Cardiac catheterization space was converted for the unit, which was intended to preserve beds in the hospital ICU for patients needing mechanical ventilation or vasoactive medication.

Interdisciplinary rounds – to assess oxygen and inflammatory marker trends, and run through a COVID care checklist – took place every day at 10 a.m.

“Consistency was the key,” Dr. Stein said.

At Weill Cornell Medical Center in New York, hospitalists helped build the COVID Recovery Unit, which was dedicated to the care of patients coming out of the ICU, said Vishwas Anand Singh, MD, MS, FHM, cochief of hospital medicine at New York Presbyterian–Lower Manhattan Hospital.

“The pandemic created an unprecedented need for critical care, and post-ICU care,” Dr. Singh said. “After extubation, patients remain very complicated and they have unique needs.”

The 30-bed COVID Recovery Unit – converted from a behavioral health unit – was designed to meet those needs. It was staffed by one lead hospitalist, 3 hospitalist physicians, 3 advanced practitioners, about 12 nurses and a neurologist, psychiatrist, and neuropsychologist.

The idea was to integrate medical care with careful attention to rehab and neuropsychological needs, Dr. Singh said. To be in the unit, patients had to be medically stable but with ongoing medical and rehabilitation needs and able to tolerate about half an hour of physical or occupational therapy each day.

The space was set up so that patients could interact with each other as well as staff, and this ability to share their experiences of trauma and recovery “led to an improved sense of psychological well-being and to healing,” according to Dr. Singh. Group therapy and meditation were also held several times a week.

“All this together, we thought we were really meeting the need for a lot of these patients from medical to psychosocial,” he said.

New York Presbyterian––Lower Manhattan Hospital also established a program called ICU Outreach to give hospitalists a “bird’s eye view” of the ICU in order to help move patients from unit to unit for optimized care. One hospitalist acted as a bridge between the ICU, the floors, and the emergency room.

The hospitalist on duty touched based with the ICU each day at 10 a.m., assessed the available beds, compiled a list of patients being discharged, met with all of the hospitalists and individual teams in inpatient and emergency services, and compiled a list of “watchers” – the sickest patients who needed help being managed.

The broad perspective was important, Dr. Singh said.

“We quickly found that each individual team or provider only knew the patients they were caring for, and the ICU Outreach person knew the whole big picture and could put the pieces together,” he said. “They could answer who was next in line for a bed, who benefited from a goals of care discussion, who could be managed on the floor with assistance. And this bridge, having this person fill this role, allowed the intensivists to focus on the patients they had in the unit.”
 

Palliative care and patient flow

Dr. Singh also described how hospitalists played an important role in palliative care for COVID patients. The hospital medicine team offered hospitalist palliative care services, which included COVIDtalk, a course on communicating about end of life, which helped to expand the pool of palliative care providers. Those trained were taught that these difficult conversations had to be honest and clear, with the goals of care addressed very early in the admission, should a patient decompensate soon after arrival.

A palliative “rapid response team” included a virtual hospitalist, a palliative care nurse practitioner, and a virtual psychiatrist – a team available 24 hours a day to have longer conversations so that clinicians could better tend to their patients when the in-person palliative care service was stretched thin, or at off hours like the middle of the night.

These innovations not only helped serve patients and families better, but also gave hospitalists training and experience in palliative care.

At Roper Hospital, Dr. Stein explained how hospitalists helped improve management of COVID patient flow. Depending on the time of day and the staffing on duty, there could be considerable confusion about where patients should go after the ED, or the COVID progressive unit, or the floor.

Hospitalists helped develop hospitalwide algorithms for escalating and deescalating acuity, Dr. Stein said, providing a “shared mental model for where a patient should go.”

“There are many ways hospitalists can and did rise to meet the unique demands of COVID,” Dr. Singh said, “whether it was innovating a new unit or service or work flow or leading a multidisciplinary team to extend or support other services that may have been strained.”
 

With intensive care units stretched to their limits – and beyond – during the COVID-19 pandemic, hospitalists became more central than ever in orchestrating the response.

At SHM Converge, the annual conference of the Society of Hospital Medicine, two hospitalists shared how their teams helped to develop new critical care units and strategies for best managing and allocating care to COVID patients in the ICU.

“The pandemic has been a selective pressure on us as a specialty,” said Jason Stein, MD, SFHM, a full-time clinical hospitalist at Roper Hospital, a 332-bed facility in Charleston, S.C.

Dr. Stein explained how hospitalists at Roper helped create the Progressive Care Unit – a negative-pressure unit with 12 high-flow oxygen beds overseen by a hospital medicine team, with the help of a respiratory therapist, pharmacist, and nurses. Patients in this unit had escalating acuity – quickly increasing oxygen needs – or deescalating acuity, such as ICU transfers, Dr. Stein said. Cardiac catheterization space was converted for the unit, which was intended to preserve beds in the hospital ICU for patients needing mechanical ventilation or vasoactive medication.

Interdisciplinary rounds – to assess oxygen and inflammatory marker trends, and run through a COVID care checklist – took place every day at 10 a.m.

“Consistency was the key,” Dr. Stein said.

At Weill Cornell Medical Center in New York, hospitalists helped build the COVID Recovery Unit, which was dedicated to the care of patients coming out of the ICU, said Vishwas Anand Singh, MD, MS, FHM, cochief of hospital medicine at New York Presbyterian–Lower Manhattan Hospital.

“The pandemic created an unprecedented need for critical care, and post-ICU care,” Dr. Singh said. “After extubation, patients remain very complicated and they have unique needs.”

The 30-bed COVID Recovery Unit – converted from a behavioral health unit – was designed to meet those needs. It was staffed by one lead hospitalist, 3 hospitalist physicians, 3 advanced practitioners, about 12 nurses and a neurologist, psychiatrist, and neuropsychologist.

The idea was to integrate medical care with careful attention to rehab and neuropsychological needs, Dr. Singh said. To be in the unit, patients had to be medically stable but with ongoing medical and rehabilitation needs and able to tolerate about half an hour of physical or occupational therapy each day.

The space was set up so that patients could interact with each other as well as staff, and this ability to share their experiences of trauma and recovery “led to an improved sense of psychological well-being and to healing,” according to Dr. Singh. Group therapy and meditation were also held several times a week.

“All this together, we thought we were really meeting the need for a lot of these patients from medical to psychosocial,” he said.

New York Presbyterian––Lower Manhattan Hospital also established a program called ICU Outreach to give hospitalists a “bird’s eye view” of the ICU in order to help move patients from unit to unit for optimized care. One hospitalist acted as a bridge between the ICU, the floors, and the emergency room.

The hospitalist on duty touched based with the ICU each day at 10 a.m., assessed the available beds, compiled a list of patients being discharged, met with all of the hospitalists and individual teams in inpatient and emergency services, and compiled a list of “watchers” – the sickest patients who needed help being managed.

The broad perspective was important, Dr. Singh said.

“We quickly found that each individual team or provider only knew the patients they were caring for, and the ICU Outreach person knew the whole big picture and could put the pieces together,” he said. “They could answer who was next in line for a bed, who benefited from a goals of care discussion, who could be managed on the floor with assistance. And this bridge, having this person fill this role, allowed the intensivists to focus on the patients they had in the unit.”
 

Palliative care and patient flow

Dr. Singh also described how hospitalists played an important role in palliative care for COVID patients. The hospital medicine team offered hospitalist palliative care services, which included COVIDtalk, a course on communicating about end of life, which helped to expand the pool of palliative care providers. Those trained were taught that these difficult conversations had to be honest and clear, with the goals of care addressed very early in the admission, should a patient decompensate soon after arrival.

A palliative “rapid response team” included a virtual hospitalist, a palliative care nurse practitioner, and a virtual psychiatrist – a team available 24 hours a day to have longer conversations so that clinicians could better tend to their patients when the in-person palliative care service was stretched thin, or at off hours like the middle of the night.

These innovations not only helped serve patients and families better, but also gave hospitalists training and experience in palliative care.

At Roper Hospital, Dr. Stein explained how hospitalists helped improve management of COVID patient flow. Depending on the time of day and the staffing on duty, there could be considerable confusion about where patients should go after the ED, or the COVID progressive unit, or the floor.

Hospitalists helped develop hospitalwide algorithms for escalating and deescalating acuity, Dr. Stein said, providing a “shared mental model for where a patient should go.”

“There are many ways hospitalists can and did rise to meet the unique demands of COVID,” Dr. Singh said, “whether it was innovating a new unit or service or work flow or leading a multidisciplinary team to extend or support other services that may have been strained.”
 

Compared with placebo, sporebiotics significantly reduced postprandial distress, epigastric pain, and several other symptoms of functional dyspepsia, reported lead author Lucas Wauters, MD, PhD, of University Hospitals Leuven (Belgium), and colleagues.

“Acid suppressive or first-line therapy with PPIs [proton pump inhibitors] for functional dyspepsia has limited efficacy and potential long-term side effects,” the investigators reported at the annual Digestive Disease Week® (DDW). “Spore-forming bacteria or sporebiotics may be effective for postprandial distress and epigastric pain or burning symptoms, offering benefits which may differ in relation to PPI intake.”
 

Sporebiotics improve variety of symptoms

To test this hypothesis, the investigators recruited 68 patients with functional dyspepsia who had similar characteristics at baseline. Half of the participants (n = 34) were taking PPIs.

Patients were randomized in a 1:1 ratio to receive 2.5 x 10⁹ CFU of Bacillus coagulans MY01 and B. subtilis MY02 twice daily for 8 weeks, or matching placebo. Following this period, an additional 8-week open-label regimen was instituted, during which time all patients received sporebiotics. Throughout the study, a daily diary was used to self-report symptoms.

The primary outcome, measured at 8 weeks, was clinical response, defined by a decrease in weekly postprandial distress symptoms greater than 0.7 among patients who had a baseline score greater than 1.0. Secondary outcomes included change in postprandial distress symptoms greater than 0.5 (minimal clinical response), as well as changes in cardinal epigastric pain, cardinal postprandial distress, and other symptoms. At baseline and 8 weeks, patients taking PPIs underwent a ¹⁴C-glycocolic acid breath test to detect changes in small intestinal bacterial overgrowth.

At 8 weeks, a clinical response was observed in 48% of patients taking sporebiotics, compared with 20% of those in the placebo group (P = .03). At the same time point, 56% of patients in the treatment group had a minimal clinical response versus 27% in the control group (P = .03).

Spore-forming probiotics were also associated with significantly greater improvements in cardinal postprandial distress, cardinal epigastric pain, postprandial fullness, and upper abdominal pain. A trend toward improvement in upper abdominal bloating was also seen (P = .07).

Among patients taking PPIs, baseline rates of positivity for bile acid breath testing were similar between those in the sporebiotic and placebo group, at 18% and 25%, respectively (P = .29). After 8 weeks, however, patients taking spore-forming probiotics had a significantly lower rate of bile acid breath test positivity (7% vs. 36%; P = .04), suggesting improvements in small intestinal bacterial overgrowth.

In the open-label portion of the trial, patients in the treatment group maintained improvements in postprandial distress. Patients who switched from placebo to sporebiotics had a significant reduction in postprandial distress symptoms.

At 8 weeks, sporebiotics were associated with a trend toward fewer side effects of any kind (16% vs. 33%; P = .09), while rates of GI-specific side effects were comparable between groups, at 3% and 15% for sporebiotics and placebo, respectively (P = .2).“Spore-forming probiotics are effective and safe in patients with functional dyspepsia, decreasing both postprandial distress and epigastric pain symptoms,” the investigators concluded. “In patients [taking PPIs], sporebiotics decrease the percentage of positive bile acid breath tests, suggesting a reduction of small intestinal bacterial overgrowth.”

Results are promising, but big questions remain

Pankaj Jay Pasricha, MBBS, MD, vice chair of medicine innovation and commercialization at Johns Hopkins and director of the Johns Hopkins Center for Neurogastroenterology, Baltimore, called the results “very encouraging.”

“This [study] is the first of its kind for this condition,” Dr. Pasricha said in an interview. “It will be very interesting to see whether others can reproduce these findings, and whether [these improvements] are sustained beyond the first few weeks or months.”

He noted that determining associated mechanisms of action could potentially open up new lines of therapy, and provide greater understanding of pathophysiology, which is currently lacking.

“We don’t fully understand the pathophysiology [of functional dyspepsia],” Dr. Pasricha said. “If you don’t understand the pathophysiology, then it’s difficult to identify the right molecular target to address the root cause. Instead, we use a variety of symptomatic treatments that aren’t actually addressing the root cause, but studies like this may help us gain some insight into the cause of the problem, and if it is in fact a fundamental imbalance in the intestinal microbiota, then this would be a rational approach.”

It’s unclear how sporebiotics may improve functional dyspepsia, Dr. Pasricha noted. He proposed three possible mechanisms: the bacteria could be colonizing the intestine, they could be releasing products as they pass through the intestine that have a therapeutic effect, or they may be altering bile acid metabolism in the colon or having some other effect there.

“It’s speculative on my part to say how it works,” Dr. Pasricha said. “All the dots remain to be connected. But it’s a good start, and an outstanding group of investigators.”Dr. Wauters and colleagues reported no conflicts of interest. Dr. Pasricha disclosed a relationship with Pendulum Therapeutics.

Compared with placebo, sporebiotics significantly reduced postprandial distress, epigastric pain, and several other symptoms of functional dyspepsia, reported lead author Lucas Wauters, MD, PhD, of University Hospitals Leuven (Belgium), and colleagues.

“Acid suppressive or first-line therapy with PPIs [proton pump inhibitors] for functional dyspepsia has limited efficacy and potential long-term side effects,” the investigators reported at the annual Digestive Disease Week® (DDW). “Spore-forming bacteria or sporebiotics may be effective for postprandial distress and epigastric pain or burning symptoms, offering benefits which may differ in relation to PPI intake.”
 

Sporebiotics improve variety of symptoms

To test this hypothesis, the investigators recruited 68 patients with functional dyspepsia who had similar characteristics at baseline. Half of the participants (n = 34) were taking PPIs.

Patients were randomized in a 1:1 ratio to receive 2.5 x 10⁹ CFU of Bacillus coagulans MY01 and B. subtilis MY02 twice daily for 8 weeks, or matching placebo. Following this period, an additional 8-week open-label regimen was instituted, during which time all patients received sporebiotics. Throughout the study, a daily diary was used to self-report symptoms.

The primary outcome, measured at 8 weeks, was clinical response, defined by a decrease in weekly postprandial distress symptoms greater than 0.7 among patients who had a baseline score greater than 1.0. Secondary outcomes included change in postprandial distress symptoms greater than 0.5 (minimal clinical response), as well as changes in cardinal epigastric pain, cardinal postprandial distress, and other symptoms. At baseline and 8 weeks, patients taking PPIs underwent a ¹⁴C-glycocolic acid breath test to detect changes in small intestinal bacterial overgrowth.

At 8 weeks, a clinical response was observed in 48% of patients taking sporebiotics, compared with 20% of those in the placebo group (P = .03). At the same time point, 56% of patients in the treatment group had a minimal clinical response versus 27% in the control group (P = .03).

Spore-forming probiotics were also associated with significantly greater improvements in cardinal postprandial distress, cardinal epigastric pain, postprandial fullness, and upper abdominal pain. A trend toward improvement in upper abdominal bloating was also seen (P = .07).

Among patients taking PPIs, baseline rates of positivity for bile acid breath testing were similar between those in the sporebiotic and placebo group, at 18% and 25%, respectively (P = .29). After 8 weeks, however, patients taking spore-forming probiotics had a significantly lower rate of bile acid breath test positivity (7% vs. 36%; P = .04), suggesting improvements in small intestinal bacterial overgrowth.

In the open-label portion of the trial, patients in the treatment group maintained improvements in postprandial distress. Patients who switched from placebo to sporebiotics had a significant reduction in postprandial distress symptoms.

At 8 weeks, sporebiotics were associated with a trend toward fewer side effects of any kind (16% vs. 33%; P = .09), while rates of GI-specific side effects were comparable between groups, at 3% and 15% for sporebiotics and placebo, respectively (P = .2).“Spore-forming probiotics are effective and safe in patients with functional dyspepsia, decreasing both postprandial distress and epigastric pain symptoms,” the investigators concluded. “In patients [taking PPIs], sporebiotics decrease the percentage of positive bile acid breath tests, suggesting a reduction of small intestinal bacterial overgrowth.”

Results are promising, but big questions remain

Pankaj Jay Pasricha, MBBS, MD, vice chair of medicine innovation and commercialization at Johns Hopkins and director of the Johns Hopkins Center for Neurogastroenterology, Baltimore, called the results “very encouraging.”

“This [study] is the first of its kind for this condition,” Dr. Pasricha said in an interview. “It will be very interesting to see whether others can reproduce these findings, and whether [these improvements] are sustained beyond the first few weeks or months.”

He noted that determining associated mechanisms of action could potentially open up new lines of therapy, and provide greater understanding of pathophysiology, which is currently lacking.

“We don’t fully understand the pathophysiology [of functional dyspepsia],” Dr. Pasricha said. “If you don’t understand the pathophysiology, then it’s difficult to identify the right molecular target to address the root cause. Instead, we use a variety of symptomatic treatments that aren’t actually addressing the root cause, but studies like this may help us gain some insight into the cause of the problem, and if it is in fact a fundamental imbalance in the intestinal microbiota, then this would be a rational approach.”

It’s unclear how sporebiotics may improve functional dyspepsia, Dr. Pasricha noted. He proposed three possible mechanisms: the bacteria could be colonizing the intestine, they could be releasing products as they pass through the intestine that have a therapeutic effect, or they may be altering bile acid metabolism in the colon or having some other effect there.

“It’s speculative on my part to say how it works,” Dr. Pasricha said. “All the dots remain to be connected. But it’s a good start, and an outstanding group of investigators.”Dr. Wauters and colleagues reported no conflicts of interest. Dr. Pasricha disclosed a relationship with Pendulum Therapeutics.

Compared with placebo, sporebiotics significantly reduced postprandial distress, epigastric pain, and several other symptoms of functional dyspepsia, reported lead author Lucas Wauters, MD, PhD, of University Hospitals Leuven (Belgium), and colleagues.

“Acid suppressive or first-line therapy with PPIs [proton pump inhibitors] for functional dyspepsia has limited efficacy and potential long-term side effects,” the investigators reported at the annual Digestive Disease Week® (DDW). “Spore-forming bacteria or sporebiotics may be effective for postprandial distress and epigastric pain or burning symptoms, offering benefits which may differ in relation to PPI intake.”
 

Sporebiotics improve variety of symptoms

To test this hypothesis, the investigators recruited 68 patients with functional dyspepsia who had similar characteristics at baseline. Half of the participants (n = 34) were taking PPIs.

Patients were randomized in a 1:1 ratio to receive 2.5 x 10⁹ CFU of Bacillus coagulans MY01 and B. subtilis MY02 twice daily for 8 weeks, or matching placebo. Following this period, an additional 8-week open-label regimen was instituted, during which time all patients received sporebiotics. Throughout the study, a daily diary was used to self-report symptoms.

The primary outcome, measured at 8 weeks, was clinical response, defined by a decrease in weekly postprandial distress symptoms greater than 0.7 among patients who had a baseline score greater than 1.0. Secondary outcomes included change in postprandial distress symptoms greater than 0.5 (minimal clinical response), as well as changes in cardinal epigastric pain, cardinal postprandial distress, and other symptoms. At baseline and 8 weeks, patients taking PPIs underwent a ¹⁴C-glycocolic acid breath test to detect changes in small intestinal bacterial overgrowth.

At 8 weeks, a clinical response was observed in 48% of patients taking sporebiotics, compared with 20% of those in the placebo group (P = .03). At the same time point, 56% of patients in the treatment group had a minimal clinical response versus 27% in the control group (P = .03).

Spore-forming probiotics were also associated with significantly greater improvements in cardinal postprandial distress, cardinal epigastric pain, postprandial fullness, and upper abdominal pain. A trend toward improvement in upper abdominal bloating was also seen (P = .07).

Among patients taking PPIs, baseline rates of positivity for bile acid breath testing were similar between those in the sporebiotic and placebo group, at 18% and 25%, respectively (P = .29). After 8 weeks, however, patients taking spore-forming probiotics had a significantly lower rate of bile acid breath test positivity (7% vs. 36%; P = .04), suggesting improvements in small intestinal bacterial overgrowth.

In the open-label portion of the trial, patients in the treatment group maintained improvements in postprandial distress. Patients who switched from placebo to sporebiotics had a significant reduction in postprandial distress symptoms.

At 8 weeks, sporebiotics were associated with a trend toward fewer side effects of any kind (16% vs. 33%; P = .09), while rates of GI-specific side effects were comparable between groups, at 3% and 15% for sporebiotics and placebo, respectively (P = .2).“Spore-forming probiotics are effective and safe in patients with functional dyspepsia, decreasing both postprandial distress and epigastric pain symptoms,” the investigators concluded. “In patients [taking PPIs], sporebiotics decrease the percentage of positive bile acid breath tests, suggesting a reduction of small intestinal bacterial overgrowth.”

Results are promising, but big questions remain

Pankaj Jay Pasricha, MBBS, MD, vice chair of medicine innovation and commercialization at Johns Hopkins and director of the Johns Hopkins Center for Neurogastroenterology, Baltimore, called the results “very encouraging.”

“This [study] is the first of its kind for this condition,” Dr. Pasricha said in an interview. “It will be very interesting to see whether others can reproduce these findings, and whether [these improvements] are sustained beyond the first few weeks or months.”

He noted that determining associated mechanisms of action could potentially open up new lines of therapy, and provide greater understanding of pathophysiology, which is currently lacking.

“We don’t fully understand the pathophysiology [of functional dyspepsia],” Dr. Pasricha said. “If you don’t understand the pathophysiology, then it’s difficult to identify the right molecular target to address the root cause. Instead, we use a variety of symptomatic treatments that aren’t actually addressing the root cause, but studies like this may help us gain some insight into the cause of the problem, and if it is in fact a fundamental imbalance in the intestinal microbiota, then this would be a rational approach.”

It’s unclear how sporebiotics may improve functional dyspepsia, Dr. Pasricha noted. He proposed three possible mechanisms: the bacteria could be colonizing the intestine, they could be releasing products as they pass through the intestine that have a therapeutic effect, or they may be altering bile acid metabolism in the colon or having some other effect there.

“It’s speculative on my part to say how it works,” Dr. Pasricha said. “All the dots remain to be connected. But it’s a good start, and an outstanding group of investigators.”Dr. Wauters and colleagues reported no conflicts of interest. Dr. Pasricha disclosed a relationship with Pendulum Therapeutics.

Nasogastric intubation for esophageal manometry or impedance monitoring does not generate significant aerosol particles and is associated with minimal droplet spread, according to a Belgian study presented at the annual Digestive Disease Week® (DDW). These findings suggest that standard personal protective equipment and appropriate patient positioning are likely sufficient to protect health care workers from increased risk of coronavirus transmission during tube placement and removal, reported lead author Wout Verbeure, PhD, of Leuven University Hospital, Belgium, and colleagues.

“Subsequent to the COVID-19 peak, [nasogastric tube insertion and extraction] were scaled back based on the assumption that they generate respiratory aerosol particles and droplet spread,” the investigators reported. “However, there is no scientific evidence for this theory.”

To address this knowledge gap, the investigators conducted an observational trial involving SARS-CoV-2-negative patients and including 21 insertions and removals for high-resolution manometry (HRM), plus 12 insertions and 10 removals for 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH). During the study, a Camfil City M Air Purifier was added to the examination room. This was present during 13 of the 21 HRM insertions and removals, allowing for comparison of aerosol particle measurements before and after introduction of the device.
 

The mechanics of the study

Aerosol particles (0.3-10 mcm) were measured with a Particle Measuring Systems LASAIR II Particle Counter positioned 1 cm away from the patient’s face. For both procedures, measurements were taken before, during, and up to 5 minutes after each nasogastric tube placement and removal. Additional measurements were taken while the HRM examination was being conducted.

To measure droplet spread, 1% medical fluorescein in saline was applied to each patient’s nasal cavity; droplets were visualized on a white sheet covering the patient and a white apron worn by the health care worker. The patients’ masks were kept below their noses but were covering their mouths.

“During the placement and removal of the catheter, the health care worker was always standing sideways or even behind the patient, and they always stood higher relative to the patient to ensure that when there was aerosol or droplet spread, it was not in their direction,” Dr. Verbeure said during his virtual presentation.

During placement for HRM and removal for MII-pH, aerosol particles (excluding those that were 0.3 mcm), decreased significantly. Otherwise, particle counts remained stable. “This shows that these investigations do not generate additional aerosol [particles], which is good news,” Dr. Verbeure said.

When the air purifier was present, placement and examination for HRM were associated with significant reductions in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm), whereas removal caused a slight uptick in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm) that did not decline after 5 minutes. “This was actually a surprise to us,” Dr. Verbeure said. “Because we now had an air purifier present, and we expected an even lower number of particles.”

He suggested that the purifier may have been reducing particle counts during HRM examination, thereby lowering baseline values before removal, making small changes more noticeable; or the purifier may have been causing turbulence that spread particles during removal. Whether either of these hypotheses is true, Dr. Verbeure noted that particle counts were never higher than at the start of the examination. Fluorescein visualization showed “surprisingly little droplet spread,” Dr. Verbeure said, apart from some contamination around the patient’s neck.

“Esophageal investigations do not seem to generate additional [aerosol] particles,” Dr. Verbeure concluded. “So wearing the recommended protective gear and also considering the right positioning of the health care worker relative to the patient is important to keep performing this daily clinical routine.” To avoid droplet spread, health care workers should “be aware of the [patient’s] neck region and the direction of the catheter,” Dr. Verbeure added.
 

SORTing the results

According to Mahdi Najafi, MD, associate professor in the department of anesthesiology at Tehran University of Medical Sciences, Iran, and adjunct professor at Schulich School of Medicine & Dentistry, Western University, London, Ontario, the findings offer valuable insights. “[This study] is very important for at least two reasons: The extent of using this procedure in patient care, especially in the critical care setting, and the paucity of information for COVID-19 transmission and route of transmission as well,” Dr. Najafi said in an interview.

Yet he cautioned against generalizing the results. “We cannot extend the results to all nasogastric tube intubations,” Dr. Najafi said. “There are reasons for that. The tube for manometry is delicate and flexible, while the nasogastric tube used for drainage and GI pressure release – which is used commonly in intensive care and the operating room – is larger and rather rigid. Moreover, the patient is awake and conscious for manometry while the other procedures are done in sedated or unconscious patients.”

He noted that nasogastric intubation is more challenging in unconscious patients, and often requires a laryngoscope and/or Magill forceps. “The result [of using these instruments] is coughing, which is undoubtedly the most important cause of aerosol generation,” Dr. Najafi said. “It can be regarded as a drawback to this study as well. The authors would be better to report the number and/or severity of the airway reactions during the procedures, which are the main source of droplets and aerosols.”

To reduce risk of coronavirus transmission during nasogastric intubation of unconscious patients, Dr. Najafi recommended the SORT (Sniffing position, nasogastric tube Orientation, contralateral Rotation, and Twisting movement) maneuver, which he introduced in 2016 for use in critical care and operating room settings.

“The employment of anatomical approach and avoiding equipment for intubation were devised to increase the level of safety and decrease hazards and adverse effects,” Dr. Najafi said of the SORT maneuver. “The procedure needs to be done step-by-step and as smooth as possible.”

In a recent study, the SORT maneuver was compared with nasogastric intubation using neck flexion lateral pressure in critically ill patients. The investigators concluded that the SORT maneuver is “a promising method” notable for its simple technique, and suggested that more trials are needed.

The investigators and Dr. Najafi reported no conflicts of interest.

Nasogastric intubation for esophageal manometry or impedance monitoring does not generate significant aerosol particles and is associated with minimal droplet spread, according to a Belgian study presented at the annual Digestive Disease Week® (DDW). These findings suggest that standard personal protective equipment and appropriate patient positioning are likely sufficient to protect health care workers from increased risk of coronavirus transmission during tube placement and removal, reported lead author Wout Verbeure, PhD, of Leuven University Hospital, Belgium, and colleagues.

“Subsequent to the COVID-19 peak, [nasogastric tube insertion and extraction] were scaled back based on the assumption that they generate respiratory aerosol particles and droplet spread,” the investigators reported. “However, there is no scientific evidence for this theory.”

To address this knowledge gap, the investigators conducted an observational trial involving SARS-CoV-2-negative patients and including 21 insertions and removals for high-resolution manometry (HRM), plus 12 insertions and 10 removals for 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH). During the study, a Camfil City M Air Purifier was added to the examination room. This was present during 13 of the 21 HRM insertions and removals, allowing for comparison of aerosol particle measurements before and after introduction of the device.
 

The mechanics of the study

Aerosol particles (0.3-10 mcm) were measured with a Particle Measuring Systems LASAIR II Particle Counter positioned 1 cm away from the patient’s face. For both procedures, measurements were taken before, during, and up to 5 minutes after each nasogastric tube placement and removal. Additional measurements were taken while the HRM examination was being conducted.

To measure droplet spread, 1% medical fluorescein in saline was applied to each patient’s nasal cavity; droplets were visualized on a white sheet covering the patient and a white apron worn by the health care worker. The patients’ masks were kept below their noses but were covering their mouths.

“During the placement and removal of the catheter, the health care worker was always standing sideways or even behind the patient, and they always stood higher relative to the patient to ensure that when there was aerosol or droplet spread, it was not in their direction,” Dr. Verbeure said during his virtual presentation.

During placement for HRM and removal for MII-pH, aerosol particles (excluding those that were 0.3 mcm), decreased significantly. Otherwise, particle counts remained stable. “This shows that these investigations do not generate additional aerosol [particles], which is good news,” Dr. Verbeure said.

When the air purifier was present, placement and examination for HRM were associated with significant reductions in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm), whereas removal caused a slight uptick in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm) that did not decline after 5 minutes. “This was actually a surprise to us,” Dr. Verbeure said. “Because we now had an air purifier present, and we expected an even lower number of particles.”

He suggested that the purifier may have been reducing particle counts during HRM examination, thereby lowering baseline values before removal, making small changes more noticeable; or the purifier may have been causing turbulence that spread particles during removal. Whether either of these hypotheses is true, Dr. Verbeure noted that particle counts were never higher than at the start of the examination. Fluorescein visualization showed “surprisingly little droplet spread,” Dr. Verbeure said, apart from some contamination around the patient’s neck.

“Esophageal investigations do not seem to generate additional [aerosol] particles,” Dr. Verbeure concluded. “So wearing the recommended protective gear and also considering the right positioning of the health care worker relative to the patient is important to keep performing this daily clinical routine.” To avoid droplet spread, health care workers should “be aware of the [patient’s] neck region and the direction of the catheter,” Dr. Verbeure added.
 

SORTing the results

According to Mahdi Najafi, MD, associate professor in the department of anesthesiology at Tehran University of Medical Sciences, Iran, and adjunct professor at Schulich School of Medicine & Dentistry, Western University, London, Ontario, the findings offer valuable insights. “[This study] is very important for at least two reasons: The extent of using this procedure in patient care, especially in the critical care setting, and the paucity of information for COVID-19 transmission and route of transmission as well,” Dr. Najafi said in an interview.

Yet he cautioned against generalizing the results. “We cannot extend the results to all nasogastric tube intubations,” Dr. Najafi said. “There are reasons for that. The tube for manometry is delicate and flexible, while the nasogastric tube used for drainage and GI pressure release – which is used commonly in intensive care and the operating room – is larger and rather rigid. Moreover, the patient is awake and conscious for manometry while the other procedures are done in sedated or unconscious patients.”

He noted that nasogastric intubation is more challenging in unconscious patients, and often requires a laryngoscope and/or Magill forceps. “The result [of using these instruments] is coughing, which is undoubtedly the most important cause of aerosol generation,” Dr. Najafi said. “It can be regarded as a drawback to this study as well. The authors would be better to report the number and/or severity of the airway reactions during the procedures, which are the main source of droplets and aerosols.”

To reduce risk of coronavirus transmission during nasogastric intubation of unconscious patients, Dr. Najafi recommended the SORT (Sniffing position, nasogastric tube Orientation, contralateral Rotation, and Twisting movement) maneuver, which he introduced in 2016 for use in critical care and operating room settings.

“The employment of anatomical approach and avoiding equipment for intubation were devised to increase the level of safety and decrease hazards and adverse effects,” Dr. Najafi said of the SORT maneuver. “The procedure needs to be done step-by-step and as smooth as possible.”

In a recent study, the SORT maneuver was compared with nasogastric intubation using neck flexion lateral pressure in critically ill patients. The investigators concluded that the SORT maneuver is “a promising method” notable for its simple technique, and suggested that more trials are needed.

The investigators and Dr. Najafi reported no conflicts of interest.

Nasogastric intubation for esophageal manometry or impedance monitoring does not generate significant aerosol particles and is associated with minimal droplet spread, according to a Belgian study presented at the annual Digestive Disease Week® (DDW). These findings suggest that standard personal protective equipment and appropriate patient positioning are likely sufficient to protect health care workers from increased risk of coronavirus transmission during tube placement and removal, reported lead author Wout Verbeure, PhD, of Leuven University Hospital, Belgium, and colleagues.

“Subsequent to the COVID-19 peak, [nasogastric tube insertion and extraction] were scaled back based on the assumption that they generate respiratory aerosol particles and droplet spread,” the investigators reported. “However, there is no scientific evidence for this theory.”

To address this knowledge gap, the investigators conducted an observational trial involving SARS-CoV-2-negative patients and including 21 insertions and removals for high-resolution manometry (HRM), plus 12 insertions and 10 removals for 24-hour multichannel intraluminal impedance-pH monitoring (MII-pH). During the study, a Camfil City M Air Purifier was added to the examination room. This was present during 13 of the 21 HRM insertions and removals, allowing for comparison of aerosol particle measurements before and after introduction of the device.
 

The mechanics of the study

Aerosol particles (0.3-10 mcm) were measured with a Particle Measuring Systems LASAIR II Particle Counter positioned 1 cm away from the patient’s face. For both procedures, measurements were taken before, during, and up to 5 minutes after each nasogastric tube placement and removal. Additional measurements were taken while the HRM examination was being conducted.

To measure droplet spread, 1% medical fluorescein in saline was applied to each patient’s nasal cavity; droplets were visualized on a white sheet covering the patient and a white apron worn by the health care worker. The patients’ masks were kept below their noses but were covering their mouths.

“During the placement and removal of the catheter, the health care worker was always standing sideways or even behind the patient, and they always stood higher relative to the patient to ensure that when there was aerosol or droplet spread, it was not in their direction,” Dr. Verbeure said during his virtual presentation.

During placement for HRM and removal for MII-pH, aerosol particles (excluding those that were 0.3 mcm), decreased significantly. Otherwise, particle counts remained stable. “This shows that these investigations do not generate additional aerosol [particles], which is good news,” Dr. Verbeure said.

When the air purifier was present, placement and examination for HRM were associated with significant reductions in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm), whereas removal caused a slight uptick in aerosol particles (excluding those that were 0.3 mcm or 0.5 mcm) that did not decline after 5 minutes. “This was actually a surprise to us,” Dr. Verbeure said. “Because we now had an air purifier present, and we expected an even lower number of particles.”

He suggested that the purifier may have been reducing particle counts during HRM examination, thereby lowering baseline values before removal, making small changes more noticeable; or the purifier may have been causing turbulence that spread particles during removal. Whether either of these hypotheses is true, Dr. Verbeure noted that particle counts were never higher than at the start of the examination. Fluorescein visualization showed “surprisingly little droplet spread,” Dr. Verbeure said, apart from some contamination around the patient’s neck.

“Esophageal investigations do not seem to generate additional [aerosol] particles,” Dr. Verbeure concluded. “So wearing the recommended protective gear and also considering the right positioning of the health care worker relative to the patient is important to keep performing this daily clinical routine.” To avoid droplet spread, health care workers should “be aware of the [patient’s] neck region and the direction of the catheter,” Dr. Verbeure added.
 

SORTing the results

According to Mahdi Najafi, MD, associate professor in the department of anesthesiology at Tehran University of Medical Sciences, Iran, and adjunct professor at Schulich School of Medicine & Dentistry, Western University, London, Ontario, the findings offer valuable insights. “[This study] is very important for at least two reasons: The extent of using this procedure in patient care, especially in the critical care setting, and the paucity of information for COVID-19 transmission and route of transmission as well,” Dr. Najafi said in an interview.

Yet he cautioned against generalizing the results. “We cannot extend the results to all nasogastric tube intubations,” Dr. Najafi said. “There are reasons for that. The tube for manometry is delicate and flexible, while the nasogastric tube used for drainage and GI pressure release – which is used commonly in intensive care and the operating room – is larger and rather rigid. Moreover, the patient is awake and conscious for manometry while the other procedures are done in sedated or unconscious patients.”

He noted that nasogastric intubation is more challenging in unconscious patients, and often requires a laryngoscope and/or Magill forceps. “The result [of using these instruments] is coughing, which is undoubtedly the most important cause of aerosol generation,” Dr. Najafi said. “It can be regarded as a drawback to this study as well. The authors would be better to report the number and/or severity of the airway reactions during the procedures, which are the main source of droplets and aerosols.”

To reduce risk of coronavirus transmission during nasogastric intubation of unconscious patients, Dr. Najafi recommended the SORT (Sniffing position, nasogastric tube Orientation, contralateral Rotation, and Twisting movement) maneuver, which he introduced in 2016 for use in critical care and operating room settings.

“The employment of anatomical approach and avoiding equipment for intubation were devised to increase the level of safety and decrease hazards and adverse effects,” Dr. Najafi said of the SORT maneuver. “The procedure needs to be done step-by-step and as smooth as possible.”

In a recent study, the SORT maneuver was compared with nasogastric intubation using neck flexion lateral pressure in critically ill patients. The investigators concluded that the SORT maneuver is “a promising method” notable for its simple technique, and suggested that more trials are needed.

The investigators and Dr. Najafi reported no conflicts of interest.

Adding bevacizumab (Avastin) to second-line osimertinib (Tagrisso) provided no overall benefit versus osimertinib alone for advanced non–small cell lung cancer with epidermal growth factor receptor (EGFR) and T790M mutations in the randomized, open-label, phase 2 European Thoracic Oncology Platform (ETOP) BOOSTER trial.

The combination treatment did, however, show superiority over osimertinib alone in current and former smokers in the study, say the investigators.

“The use of osimertinib and bevacizumab was associated with longer progression-free survival in the subgroup of patients who were former or current smokers [hazard ratio, 0.57],” Ross Soo, MD, reported during a European Society of Medical Oncology virtual plenary session.

The findings were also published May 12, 2021, in Annals of Oncology.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) with selective activity toward EGFR-sensitizing and T790M resistance mutations, is the standard treatment in this patient population, but progression inevitably occurs.

Based on preclinical studies suggesting that the angiogenic pathway is implicated in EGFR TKI resistance, the current study was designed to assess the efficacy and safety of combined osimertinib and the antiangiogenic agent bevacizumab versus osimertinib alone in patients who progressed on prior EGFR TKI therapy, explained Dr. Soo, a senior consultant in the department of hematology-oncology at the National University Cancer Institute, Singapore.

Median overall progression-free survival (PFS) at a median follow-up of 34 months was 15.4 months versus 12.3 months in 78 patients in the bevacizumab/osimertinib combination therapy group and 77 patients in the osimertinib monotherapy group, respectively – which translated into a nonstatistically significant difference (HR, 0.96).

In the current and former smoker subgroup, median PFS was 16.5 months and 8.4 months with combination versus monotherapy, respectively (HR, .57), Dr. Soo said.

An exploratory analysis showed that the effect of the combination therapy was statistically different in current/former smokers versus never-smokers (HR, 0.52 and 1.47, respectively), he noted.

For the secondary study endpoint of overall survival (OS), no significant difference was seen overall with the combination versus monotherapy (24.0 vs. 24.3 months; HR, 1.03) or the current or former smoker subgroup (HR, 0.54).

However, in the current and former smoker subgroup, the effect of the treatment combination “was in the same direction and similar in magnitude to progression-free survival, but did not reach statistical significance,” Dr. Soo noted.

The exploratory analysis showed OS HRs of 0.59 and 1.54 in the current/former smokers versus never-smokers, respectively.
 

Smoking data may be important

Study participants were adults with a median age of 67 years who had exon 19 del or L858R and T790M mutation at progression on prior EGFR TKI therapy. Most (62%) were women and 40% were current or former smokers. They were enrolled between 2017 and 2019 from 22 centers in six countries and randomly assigned to receive bevacizumab at a dose of 15 mg/kg intravenously on day 1 every 3 weeks plus osimertinib at 80 mg daily or osimertinib alone.

The median time to treatment failure was 8.2 months in the combination therapy, (with TTF of 8.2 months for bevacizumab and 12.4 for osimertinib), compared with 10.8 months for osimertinib monotherapy.

Overall response was 55% in both groups, and disease control rates were 90% and 82% in the groups, respectively. Median duration of response was 14.5 months versus 16.6 months, Dr. Soo said.

Grade 3 or greater treatment-related adverse events occurred in 47% and 18% of patients in the combination and monotherapy groups. The most frequent adverse event in both groups was diarrhea. Proteinuria and hypertension occurred more often in the combination-therapy group.

Based on these findings, osimertinib remains the standard of care in patients with advanced NSCLC with acquired EGFR TKI resistance harboring EGFR T790M mutations, he concluded.

The findings are in line with those from prior smaller studies, and are “hypothesis generating,” said invited discussant Edward B. Garon, MD, professor and director of the thoracic oncology program at the University of California, Los Angeles.

The new data are hypothesis generating and will help in analyzing other studies to determine whether there is a difference based on smoking history, he said. 

Dr. Garon also noted that there has been increasing interest in similar combination approaches in the frontline setting, but to date there is little to support frontline use.

“It is certainly a situation where there is room for studies exploring other approaches in the frontline setting,” he concluded.

This study was supported by Astra Zeneca and Roche. Dr. Soo reported financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Lilly, Merck, Novartis, Otsuka, Pfizer, Roche, Synthorx, Taiho, Takeda, and Yuhan. Dr. Garon reported relationships with ABL-Bio, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dracen Pharmaceuticals, Dynavax Technologies, Eli Lilly, EMD Serono, Eisai, Genentech, GlaxoSmithKline, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Natera, Neon, Novartis, Regeneron, Sanofi, Shionogi, and Xilio.

A version of this article first appeared on Medscape.com.

Adding bevacizumab (Avastin) to second-line osimertinib (Tagrisso) provided no overall benefit versus osimertinib alone for advanced non–small cell lung cancer with epidermal growth factor receptor (EGFR) and T790M mutations in the randomized, open-label, phase 2 European Thoracic Oncology Platform (ETOP) BOOSTER trial.

The combination treatment did, however, show superiority over osimertinib alone in current and former smokers in the study, say the investigators.

“The use of osimertinib and bevacizumab was associated with longer progression-free survival in the subgroup of patients who were former or current smokers [hazard ratio, 0.57],” Ross Soo, MD, reported during a European Society of Medical Oncology virtual plenary session.

The findings were also published May 12, 2021, in Annals of Oncology.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) with selective activity toward EGFR-sensitizing and T790M resistance mutations, is the standard treatment in this patient population, but progression inevitably occurs.

Based on preclinical studies suggesting that the angiogenic pathway is implicated in EGFR TKI resistance, the current study was designed to assess the efficacy and safety of combined osimertinib and the antiangiogenic agent bevacizumab versus osimertinib alone in patients who progressed on prior EGFR TKI therapy, explained Dr. Soo, a senior consultant in the department of hematology-oncology at the National University Cancer Institute, Singapore.

Median overall progression-free survival (PFS) at a median follow-up of 34 months was 15.4 months versus 12.3 months in 78 patients in the bevacizumab/osimertinib combination therapy group and 77 patients in the osimertinib monotherapy group, respectively – which translated into a nonstatistically significant difference (HR, 0.96).

In the current and former smoker subgroup, median PFS was 16.5 months and 8.4 months with combination versus monotherapy, respectively (HR, .57), Dr. Soo said.

An exploratory analysis showed that the effect of the combination therapy was statistically different in current/former smokers versus never-smokers (HR, 0.52 and 1.47, respectively), he noted.

For the secondary study endpoint of overall survival (OS), no significant difference was seen overall with the combination versus monotherapy (24.0 vs. 24.3 months; HR, 1.03) or the current or former smoker subgroup (HR, 0.54).

However, in the current and former smoker subgroup, the effect of the treatment combination “was in the same direction and similar in magnitude to progression-free survival, but did not reach statistical significance,” Dr. Soo noted.

The exploratory analysis showed OS HRs of 0.59 and 1.54 in the current/former smokers versus never-smokers, respectively.
 

Smoking data may be important

Study participants were adults with a median age of 67 years who had exon 19 del or L858R and T790M mutation at progression on prior EGFR TKI therapy. Most (62%) were women and 40% were current or former smokers. They were enrolled between 2017 and 2019 from 22 centers in six countries and randomly assigned to receive bevacizumab at a dose of 15 mg/kg intravenously on day 1 every 3 weeks plus osimertinib at 80 mg daily or osimertinib alone.

The median time to treatment failure was 8.2 months in the combination therapy, (with TTF of 8.2 months for bevacizumab and 12.4 for osimertinib), compared with 10.8 months for osimertinib monotherapy.

Overall response was 55% in both groups, and disease control rates were 90% and 82% in the groups, respectively. Median duration of response was 14.5 months versus 16.6 months, Dr. Soo said.

Grade 3 or greater treatment-related adverse events occurred in 47% and 18% of patients in the combination and monotherapy groups. The most frequent adverse event in both groups was diarrhea. Proteinuria and hypertension occurred more often in the combination-therapy group.

Based on these findings, osimertinib remains the standard of care in patients with advanced NSCLC with acquired EGFR TKI resistance harboring EGFR T790M mutations, he concluded.

The findings are in line with those from prior smaller studies, and are “hypothesis generating,” said invited discussant Edward B. Garon, MD, professor and director of the thoracic oncology program at the University of California, Los Angeles.

The new data are hypothesis generating and will help in analyzing other studies to determine whether there is a difference based on smoking history, he said. 

Dr. Garon also noted that there has been increasing interest in similar combination approaches in the frontline setting, but to date there is little to support frontline use.

“It is certainly a situation where there is room for studies exploring other approaches in the frontline setting,” he concluded.

This study was supported by Astra Zeneca and Roche. Dr. Soo reported financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Lilly, Merck, Novartis, Otsuka, Pfizer, Roche, Synthorx, Taiho, Takeda, and Yuhan. Dr. Garon reported relationships with ABL-Bio, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dracen Pharmaceuticals, Dynavax Technologies, Eli Lilly, EMD Serono, Eisai, Genentech, GlaxoSmithKline, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Natera, Neon, Novartis, Regeneron, Sanofi, Shionogi, and Xilio.

A version of this article first appeared on Medscape.com.

Adding bevacizumab (Avastin) to second-line osimertinib (Tagrisso) provided no overall benefit versus osimertinib alone for advanced non–small cell lung cancer with epidermal growth factor receptor (EGFR) and T790M mutations in the randomized, open-label, phase 2 European Thoracic Oncology Platform (ETOP) BOOSTER trial.

The combination treatment did, however, show superiority over osimertinib alone in current and former smokers in the study, say the investigators.

“The use of osimertinib and bevacizumab was associated with longer progression-free survival in the subgroup of patients who were former or current smokers [hazard ratio, 0.57],” Ross Soo, MD, reported during a European Society of Medical Oncology virtual plenary session.

The findings were also published May 12, 2021, in Annals of Oncology.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) with selective activity toward EGFR-sensitizing and T790M resistance mutations, is the standard treatment in this patient population, but progression inevitably occurs.

Based on preclinical studies suggesting that the angiogenic pathway is implicated in EGFR TKI resistance, the current study was designed to assess the efficacy and safety of combined osimertinib and the antiangiogenic agent bevacizumab versus osimertinib alone in patients who progressed on prior EGFR TKI therapy, explained Dr. Soo, a senior consultant in the department of hematology-oncology at the National University Cancer Institute, Singapore.

Median overall progression-free survival (PFS) at a median follow-up of 34 months was 15.4 months versus 12.3 months in 78 patients in the bevacizumab/osimertinib combination therapy group and 77 patients in the osimertinib monotherapy group, respectively – which translated into a nonstatistically significant difference (HR, 0.96).

In the current and former smoker subgroup, median PFS was 16.5 months and 8.4 months with combination versus monotherapy, respectively (HR, .57), Dr. Soo said.

An exploratory analysis showed that the effect of the combination therapy was statistically different in current/former smokers versus never-smokers (HR, 0.52 and 1.47, respectively), he noted.

For the secondary study endpoint of overall survival (OS), no significant difference was seen overall with the combination versus monotherapy (24.0 vs. 24.3 months; HR, 1.03) or the current or former smoker subgroup (HR, 0.54).

However, in the current and former smoker subgroup, the effect of the treatment combination “was in the same direction and similar in magnitude to progression-free survival, but did not reach statistical significance,” Dr. Soo noted.

The exploratory analysis showed OS HRs of 0.59 and 1.54 in the current/former smokers versus never-smokers, respectively.
 

Smoking data may be important

Study participants were adults with a median age of 67 years who had exon 19 del or L858R and T790M mutation at progression on prior EGFR TKI therapy. Most (62%) were women and 40% were current or former smokers. They were enrolled between 2017 and 2019 from 22 centers in six countries and randomly assigned to receive bevacizumab at a dose of 15 mg/kg intravenously on day 1 every 3 weeks plus osimertinib at 80 mg daily or osimertinib alone.

The median time to treatment failure was 8.2 months in the combination therapy, (with TTF of 8.2 months for bevacizumab and 12.4 for osimertinib), compared with 10.8 months for osimertinib monotherapy.

Overall response was 55% in both groups, and disease control rates were 90% and 82% in the groups, respectively. Median duration of response was 14.5 months versus 16.6 months, Dr. Soo said.

Grade 3 or greater treatment-related adverse events occurred in 47% and 18% of patients in the combination and monotherapy groups. The most frequent adverse event in both groups was diarrhea. Proteinuria and hypertension occurred more often in the combination-therapy group.

Based on these findings, osimertinib remains the standard of care in patients with advanced NSCLC with acquired EGFR TKI resistance harboring EGFR T790M mutations, he concluded.

The findings are in line with those from prior smaller studies, and are “hypothesis generating,” said invited discussant Edward B. Garon, MD, professor and director of the thoracic oncology program at the University of California, Los Angeles.

The new data are hypothesis generating and will help in analyzing other studies to determine whether there is a difference based on smoking history, he said. 

Dr. Garon also noted that there has been increasing interest in similar combination approaches in the frontline setting, but to date there is little to support frontline use.

“It is certainly a situation where there is room for studies exploring other approaches in the frontline setting,” he concluded.

This study was supported by Astra Zeneca and Roche. Dr. Soo reported financial relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Lilly, Merck, Novartis, Otsuka, Pfizer, Roche, Synthorx, Taiho, Takeda, and Yuhan. Dr. Garon reported relationships with ABL-Bio, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dracen Pharmaceuticals, Dynavax Technologies, Eli Lilly, EMD Serono, Eisai, Genentech, GlaxoSmithKline, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Natera, Neon, Novartis, Regeneron, Sanofi, Shionogi, and Xilio.

A version of this article first appeared on Medscape.com.

The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.

KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.  

The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.

It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.

“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.

Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.

“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
 

Details of clinical data

This is an accelerated approval based on response rate data.

The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.

The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.

Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.

Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
 

Companion diagnostic tests also approved

Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.

A version of this article first appeared on Medscape.com.

The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.

KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.  

The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.

It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.

“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.

Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.

“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
 

Details of clinical data

This is an accelerated approval based on response rate data.

The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.

The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.

Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.

Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
 

Companion diagnostic tests also approved

Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.

A version of this article first appeared on Medscape.com.

The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.

KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.  

The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.

It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.

“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.

Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.

“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
 

Details of clinical data

This is an accelerated approval based on response rate data.

The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.

The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.

Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.

The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.

Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
 

Companion diagnostic tests also approved

Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.

A version of this article first appeared on Medscape.com.