CHEST Physician

Outcomes for mechanically ventilated adults with sepsis receiving light sedation were the same whether they received dexmedetomidine or propofol, according to data from a 13-center randomized, controlled, double-blind study published online Feb. 2 in the New England Journal of Medicine.

Dexmedetomidine (an alpha2-receptor agonist) and propofol (a gamma-aminobutyric acid [GABA]–receptor agonist) have similar safety profiles.

The findings from the Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure (MENDS2) trial were published on an accelerated schedule to coincide with the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Lead author Christopher G. Hughes, MD, chief of anesthesiology in critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization that previous trials have shown that dexmedetomidine is likely superior to benzodiazepines, especially in improving delirium, coma, and time on a ventilator. Until this trial, dexmedetomidine’s performance in a head-to-head comparison with propofol – the current standard-of-care agent – was not clear.

Researchers discovered that, “despite theoretical advantages of dexmedetomidine, that did not translate into the clinical realm when patients were receiving up-to-date sedation care,” he said.

Guidelines currently recommend either drug when light sedation is needed for adults on ventilators. The drugs are different in the way they affect arousability, immunity, and inflammation, but a comparison of outcomes in adults with sepsis – in terms of days alive without brain dysfunction – had never before been performed in a randomized, controlled trial.

In this trial, 422 patients were randomly assigned to receive either dexmedetomidine (0.15-1.5 mcg/kg of body weight per hour) or propofol (5-50 mcg/kg per minute). Doses were adjusted by bedside nurses (who were unblinded) to achieve specified sedation goals.

The primary outcome was days alive without delirium or coma in the 14 days of intervention. The researchers found no difference between the two groups (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval, 0.74-1.26).

There was also little difference in three secondary outcomes: ventilator-free days (adjusted median, 23.7 vs. 24.0 days; OR, 0.98); death at 90 days (38% vs. 39%; hazard ratio, 1.06); or the Telephone Interview for Cognitive Status (TICS) Total score measuring global cognition at 6 months (adjusted median score, 40.9 vs. 41.4; OR, 0.94).

Dr. Hughes said the researchers “specifically went with a high-severity-of-illness cohort that would be most likely to see an effect.”

He said the drugs have different adverse-effect profiles, so a clinician can consider those in deciding between the two, but either should be fine at baseline.

The researchers note that at least 20 million patients each year develop sepsis with severe organ dysfunction, and more than 20% receive mechanical ventilation.
 

Confirmation of current guidelines

Sandra Kane-Gill, PharmD, president-elect of SCCM, stated in an interview that she is impressed with the study design and said the results give definitive confirmation of current guidelines.

“The rigorous study design is different from previous comparative-effectiveness trials on the drugs in this group of patients,” she said.

As to what clinicians think about when choosing one over the other, Dr. Kane-Gill said that with dexmedetomidine, there may be more concern about bradycardia, whereas propofol may be associated with concerns of high triglycerides.

“There may be more comfort with use of propofol,” and dexmedetomidine can be more costly than propofol, she added, so those could be factors in decision-making as well.

Dr. Hughes said this study offers a robust look at cognition after the ICU, which is getting increasing attention.

“We had a much more extensive cognitive battery we performed on patients than in previous studies,” Dr. Hughes said, “and it’s important that we did not find a difference in either the main cognition or the other cognitive scores between the two agents.”

Enrollment was completed before the pandemic, but he said the results are relevant to COVID-19 patients because those who are on ventilators in the ICU are in a sick, septic-shock cohort.

“COVID patients would be the type of patients we enrolled in this study,” he said, “with the high severity of illness and the infection on top of being on a ventilator. We know that sedation regimens have been challenging in COVID patients.”

Dr. Hughes and Dr. Kane-Gill have disclosed no relevant financial relationships.

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

Outcomes for mechanically ventilated adults with sepsis receiving light sedation were the same whether they received dexmedetomidine or propofol, according to data from a 13-center randomized, controlled, double-blind study published online Feb. 2 in the New England Journal of Medicine.

Dexmedetomidine (an alpha2-receptor agonist) and propofol (a gamma-aminobutyric acid [GABA]–receptor agonist) have similar safety profiles.

The findings from the Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure (MENDS2) trial were published on an accelerated schedule to coincide with the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Lead author Christopher G. Hughes, MD, chief of anesthesiology in critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization that previous trials have shown that dexmedetomidine is likely superior to benzodiazepines, especially in improving delirium, coma, and time on a ventilator. Until this trial, dexmedetomidine’s performance in a head-to-head comparison with propofol – the current standard-of-care agent – was not clear.

Researchers discovered that, “despite theoretical advantages of dexmedetomidine, that did not translate into the clinical realm when patients were receiving up-to-date sedation care,” he said.

Guidelines currently recommend either drug when light sedation is needed for adults on ventilators. The drugs are different in the way they affect arousability, immunity, and inflammation, but a comparison of outcomes in adults with sepsis – in terms of days alive without brain dysfunction – had never before been performed in a randomized, controlled trial.

In this trial, 422 patients were randomly assigned to receive either dexmedetomidine (0.15-1.5 mcg/kg of body weight per hour) or propofol (5-50 mcg/kg per minute). Doses were adjusted by bedside nurses (who were unblinded) to achieve specified sedation goals.

The primary outcome was days alive without delirium or coma in the 14 days of intervention. The researchers found no difference between the two groups (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval, 0.74-1.26).

There was also little difference in three secondary outcomes: ventilator-free days (adjusted median, 23.7 vs. 24.0 days; OR, 0.98); death at 90 days (38% vs. 39%; hazard ratio, 1.06); or the Telephone Interview for Cognitive Status (TICS) Total score measuring global cognition at 6 months (adjusted median score, 40.9 vs. 41.4; OR, 0.94).

Dr. Hughes said the researchers “specifically went with a high-severity-of-illness cohort that would be most likely to see an effect.”

He said the drugs have different adverse-effect profiles, so a clinician can consider those in deciding between the two, but either should be fine at baseline.

The researchers note that at least 20 million patients each year develop sepsis with severe organ dysfunction, and more than 20% receive mechanical ventilation.
 

Confirmation of current guidelines

Sandra Kane-Gill, PharmD, president-elect of SCCM, stated in an interview that she is impressed with the study design and said the results give definitive confirmation of current guidelines.

“The rigorous study design is different from previous comparative-effectiveness trials on the drugs in this group of patients,” she said.

As to what clinicians think about when choosing one over the other, Dr. Kane-Gill said that with dexmedetomidine, there may be more concern about bradycardia, whereas propofol may be associated with concerns of high triglycerides.

“There may be more comfort with use of propofol,” and dexmedetomidine can be more costly than propofol, she added, so those could be factors in decision-making as well.

Dr. Hughes said this study offers a robust look at cognition after the ICU, which is getting increasing attention.

“We had a much more extensive cognitive battery we performed on patients than in previous studies,” Dr. Hughes said, “and it’s important that we did not find a difference in either the main cognition or the other cognitive scores between the two agents.”

Enrollment was completed before the pandemic, but he said the results are relevant to COVID-19 patients because those who are on ventilators in the ICU are in a sick, septic-shock cohort.

“COVID patients would be the type of patients we enrolled in this study,” he said, “with the high severity of illness and the infection on top of being on a ventilator. We know that sedation regimens have been challenging in COVID patients.”

Dr. Hughes and Dr. Kane-Gill have disclosed no relevant financial relationships.

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

Outcomes for mechanically ventilated adults with sepsis receiving light sedation were the same whether they received dexmedetomidine or propofol, according to data from a 13-center randomized, controlled, double-blind study published online Feb. 2 in the New England Journal of Medicine.

Dexmedetomidine (an alpha2-receptor agonist) and propofol (a gamma-aminobutyric acid [GABA]–receptor agonist) have similar safety profiles.

The findings from the Maximizing the Efficacy of Sedation and Reducing Neurological Dysfunction and Mortality in Septic Patients with Acute Respiratory Failure (MENDS2) trial were published on an accelerated schedule to coincide with the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Lead author Christopher G. Hughes, MD, chief of anesthesiology in critical care medicine at Vanderbilt University Medical Center, Nashville, Tenn., told this news organization that previous trials have shown that dexmedetomidine is likely superior to benzodiazepines, especially in improving delirium, coma, and time on a ventilator. Until this trial, dexmedetomidine’s performance in a head-to-head comparison with propofol – the current standard-of-care agent – was not clear.

Researchers discovered that, “despite theoretical advantages of dexmedetomidine, that did not translate into the clinical realm when patients were receiving up-to-date sedation care,” he said.

Guidelines currently recommend either drug when light sedation is needed for adults on ventilators. The drugs are different in the way they affect arousability, immunity, and inflammation, but a comparison of outcomes in adults with sepsis – in terms of days alive without brain dysfunction – had never before been performed in a randomized, controlled trial.

In this trial, 422 patients were randomly assigned to receive either dexmedetomidine (0.15-1.5 mcg/kg of body weight per hour) or propofol (5-50 mcg/kg per minute). Doses were adjusted by bedside nurses (who were unblinded) to achieve specified sedation goals.

The primary outcome was days alive without delirium or coma in the 14 days of intervention. The researchers found no difference between the two groups (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval, 0.74-1.26).

There was also little difference in three secondary outcomes: ventilator-free days (adjusted median, 23.7 vs. 24.0 days; OR, 0.98); death at 90 days (38% vs. 39%; hazard ratio, 1.06); or the Telephone Interview for Cognitive Status (TICS) Total score measuring global cognition at 6 months (adjusted median score, 40.9 vs. 41.4; OR, 0.94).

Dr. Hughes said the researchers “specifically went with a high-severity-of-illness cohort that would be most likely to see an effect.”

He said the drugs have different adverse-effect profiles, so a clinician can consider those in deciding between the two, but either should be fine at baseline.

The researchers note that at least 20 million patients each year develop sepsis with severe organ dysfunction, and more than 20% receive mechanical ventilation.
 

Confirmation of current guidelines

Sandra Kane-Gill, PharmD, president-elect of SCCM, stated in an interview that she is impressed with the study design and said the results give definitive confirmation of current guidelines.

“The rigorous study design is different from previous comparative-effectiveness trials on the drugs in this group of patients,” she said.

As to what clinicians think about when choosing one over the other, Dr. Kane-Gill said that with dexmedetomidine, there may be more concern about bradycardia, whereas propofol may be associated with concerns of high triglycerides.

“There may be more comfort with use of propofol,” and dexmedetomidine can be more costly than propofol, she added, so those could be factors in decision-making as well.

Dr. Hughes said this study offers a robust look at cognition after the ICU, which is getting increasing attention.

“We had a much more extensive cognitive battery we performed on patients than in previous studies,” Dr. Hughes said, “and it’s important that we did not find a difference in either the main cognition or the other cognitive scores between the two agents.”

Enrollment was completed before the pandemic, but he said the results are relevant to COVID-19 patients because those who are on ventilators in the ICU are in a sick, septic-shock cohort.

“COVID patients would be the type of patients we enrolled in this study,” he said, “with the high severity of illness and the infection on top of being on a ventilator. We know that sedation regimens have been challenging in COVID patients.”

Dr. Hughes and Dr. Kane-Gill have disclosed no relevant financial relationships.

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

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

The gout drug colchicine appears to lower the severity of COVID-19, a small new Brazilian study finds, adding to evidence that the familiar medication holds promise as a treatment for hospitalized patients.

Patients who received colchicine in this randomized, double-blinded, placebo-controlled clinical trial presented better evolution in terms of the need for supplemental oxygen and the length of hospitalisation. ... Colchicine was safe and well tolerated,” the study authors wrote in RMD Open. However, deaths were rare in the trial, they added, and it is impossible to “evaluate the capacity of colchicine to avoid admission to ICU and reduce mortality.”

The oral anti-inflammatory colchicine, widely used as treatment in rheumatic disease, was first approved in the United States 60 years ago. Researchers began to explore its potential as a COVID-19 treatment in the early months of the pandemic.

On Jan. 25, an international team of researchers reported in a press release – but not yet a published paper – that the drug seemed to reduce hospitalizations, mechanical ventilation, and deaths in the ColCORONA trial. Earlier, a much-smaller, randomized, open-label, Greek trial linked the drug to reduced time to clinical deterioration and hospital stay.

The Brazilian authors of the new study, led by Maria Isabel Lopes of the University of São Paulo’s Ribeirão Preto Medical School, randomly assigned 75 hospitalized patients with moderate to severe COVID-19 to colchicine or placebo. A total of 72 subjects completed the April-August 2020 trial: 36 received colchicine (typically 0.5 mg three times for 5 days, then 0.5 mg twice daily for 5 days; doses were adjusted in low-weight patients and those with chronic kidney disease). The other 36 received the placebo.

(In the United States, 0.6-mg tablets of generic colchicine cost as little as $1.90 each with free coupons, according to goodrx.com.)

The median age in the groups was similar (55 years); and the placebo group had more women (61% vs. 47% in the colchicine group, P = .34). All 72 patients received the same COVID-19 treatment at the time of the trial: azithromycin, hydroxychloroquine, and unfractionated heparin. Most patients, about two-thirds in both groups, also received methylprednisolone because they needed higher amounts of supplemental oxygen.

Patients in the colchicine group needed supplemental oxygen for less time: Their median time of need was 4.0 days (interquartile range [IQR], 2.0-6.0) vs. 6.5 days (IQR, 4.0-9.0) for the placebo group (P < .001). The median time for hospitalization was also lower at 7.0 days (IQR, 5.0–9.0) for the colchicine group vs. 9.0 (IQR, 7.0–12.0) for the placebo group (log rank test, 10.6; P = .001).

The researchers also reported the percentage of patients who needed supplemental oxygen at day 2 as 67% with colchicine vs. 86% with placebo, and at day 7 as 9% vs. 42% (log rank test, 10.6; P = .001). Two patients in the placebo group died, both from ventilator-associated pneumonia.

As for side effects, new or worsened diarrhea was reported more often in the colchicine group (17% vs. 6% with placebo), but the difference was not statistically significant (P = .26), and diarrhea was controlled via medication.

The researchers reported that limitations include the exclusion criteria and their inability to link colchicine to rates of ICU admissions and death.

The drug appears to help patients with COVID-19, the study authors wrote, by “inhibiting inflammasome, reducing neutrophil migration and activation, or preventing endothelial damage.”

A “well-conceived and well-designed” study

In an interview, NYU Langone Health rheumatologist Michael H. Pillinger, MD – an investigator with the ColCORONA trial – praised the Brazilian study. It “appears well-conceived and well-designed, and was enrolled at a rate that was greater than the sample size that was estimated to be needed based on power analysis,” he said.

The Brazilian study is small, he noted. (In contrast, the ColCORONA trial had 4,488 outpatient participants.) “This study differs from ColCORONA in several ways – the most important being that it is a study of inpatients with moderate to severe COVID (really mostly moderate),” he added. “ColCORONA is looking at a target audience that is much larger – outpatients with mild to moderate COVID with risk factors for hospitalization. Both questions are really important and certainly not mutually exclusive, since our care remains inadequate in both venues. This study also adds value in that several other studies have been conducted in hospital patients with enrollment criteria relatively similar to this one, and all showed benefit, but those were open-label or retrospective, and this is blinded and placebo-controlled.”
 

Using colchicine in patients with COVID-19

Should physicians turn to colchicine in patients with COVID-19? “I would rather that it still be used in the context of research until formal recommendations can be made by bodies like the NIH and CDC,” Dr. Pillinger said. “But certainly, there may be times when physicians feel compelled to treat patients off label.”

He cautioned, however, that colchicine should never be used with some other drugs. Its interaction with the antibiotic clarithromycin can be fatal, he noted. And, he said, the drug must be monitored in general since it can cause rare, severe problems.

“Overall, colchicine probably works on the overabundant inflammatory response to COVID, and it may be that it can be combined with other drugs that affect viral replication or promote immunity – e.g. vaccines,” Dr. Pillinger said. “So far, it seems as if there is no safety problem with combining colchicine with other approaches, but this has not been studied in a rigorous manner.”

Moving forward, he said, the drug’s very low price outside of the United States “could provide resource-poor countries with a way to help keep patients out of precious hospital beds – or help them go home sooner once admitted.” For now, however, “we need a large-scale inpatient study, and one is currently going on in Great Britain. We also need validation of the outpatient ColCORONA study, and studies to look at whether colchicine can work in conjunction with other strategies.”

The study was funded by grants from the São Paulo Research Foundation, Brazilian National Council for Scientific and Technological Development, and CAPES Foundation. No disclosures are reported. Dr. Pillinger reports serving as an investigator for the ColCORONA trial and receiving a unrelated investigator-initiated grant from Hikma, a colchicine manufacturer.

The United States has now reported more than 450,000 COVID-19 deaths during the pandemic, adding 3,912 more on Wednesday, according to data from Johns Hopkins University.

Daily COVID-19 deaths still remain high in the United States, though they’ve decreased slightly from the peak of 4,466 deaths on Jan. 12.

The United States also reported more than 121,000 new COVID-19 cases on Wednesday, which is down from a peak of more than 300,000 new cases on Tuesday. In total, more than 26.5 million people in the United States have been diagnosed with COVID-19, making up a quarter of the 104.5 million cases reported worldwide.

The 7-day average for COVID-19 hospitalizations and deaths continues to decline, according to the COVID Tracking Project. The 7-day average for hospitalizations is around 96,500, and the 7-day average for deaths is about 3,000. With the exception of Vermont, all states and territories have reported declines or no changes in their hospitalizations and deaths.

“We have seen the 7-day average for new deaths decrease for over a week. At the same time, states are reporting an average of 3,000 people dying per day,” the COVID Tracking Project wrote in a post on Twitter. “The data is hopeful and devastating.”

More than 2.2 million COVID-19 deaths have been reported worldwide. The United States continues to report the most deaths, followed by Brazil with 227,500, Mexico with 161,200, and India with 154,700 deaths.

The U.S. COVID-19 death toll could reach 496,000-534,000 by the end of February, according to a new forecast by the CDC, which includes models from 36 national groups. Deaths will likely decrease during the next 4 weeks, with about 11,300-22,600 deaths possibly reported during the last week of February.

The 534,000 total would equal about 1 death for every minute of the pandemic, according to CNN, given that the first U.S. death was reported on Feb. 29 last year.

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

The United States has now reported more than 450,000 COVID-19 deaths during the pandemic, adding 3,912 more on Wednesday, according to data from Johns Hopkins University.

Daily COVID-19 deaths still remain high in the United States, though they’ve decreased slightly from the peak of 4,466 deaths on Jan. 12.

The United States also reported more than 121,000 new COVID-19 cases on Wednesday, which is down from a peak of more than 300,000 new cases on Tuesday. In total, more than 26.5 million people in the United States have been diagnosed with COVID-19, making up a quarter of the 104.5 million cases reported worldwide.

The 7-day average for COVID-19 hospitalizations and deaths continues to decline, according to the COVID Tracking Project. The 7-day average for hospitalizations is around 96,500, and the 7-day average for deaths is about 3,000. With the exception of Vermont, all states and territories have reported declines or no changes in their hospitalizations and deaths.

“We have seen the 7-day average for new deaths decrease for over a week. At the same time, states are reporting an average of 3,000 people dying per day,” the COVID Tracking Project wrote in a post on Twitter. “The data is hopeful and devastating.”

More than 2.2 million COVID-19 deaths have been reported worldwide. The United States continues to report the most deaths, followed by Brazil with 227,500, Mexico with 161,200, and India with 154,700 deaths.

The U.S. COVID-19 death toll could reach 496,000-534,000 by the end of February, according to a new forecast by the CDC, which includes models from 36 national groups. Deaths will likely decrease during the next 4 weeks, with about 11,300-22,600 deaths possibly reported during the last week of February.

The 534,000 total would equal about 1 death for every minute of the pandemic, according to CNN, given that the first U.S. death was reported on Feb. 29 last year.

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

The United States has now reported more than 450,000 COVID-19 deaths during the pandemic, adding 3,912 more on Wednesday, according to data from Johns Hopkins University.

Daily COVID-19 deaths still remain high in the United States, though they’ve decreased slightly from the peak of 4,466 deaths on Jan. 12.

The United States also reported more than 121,000 new COVID-19 cases on Wednesday, which is down from a peak of more than 300,000 new cases on Tuesday. In total, more than 26.5 million people in the United States have been diagnosed with COVID-19, making up a quarter of the 104.5 million cases reported worldwide.

The 7-day average for COVID-19 hospitalizations and deaths continues to decline, according to the COVID Tracking Project. The 7-day average for hospitalizations is around 96,500, and the 7-day average for deaths is about 3,000. With the exception of Vermont, all states and territories have reported declines or no changes in their hospitalizations and deaths.

“We have seen the 7-day average for new deaths decrease for over a week. At the same time, states are reporting an average of 3,000 people dying per day,” the COVID Tracking Project wrote in a post on Twitter. “The data is hopeful and devastating.”

More than 2.2 million COVID-19 deaths have been reported worldwide. The United States continues to report the most deaths, followed by Brazil with 227,500, Mexico with 161,200, and India with 154,700 deaths.

The U.S. COVID-19 death toll could reach 496,000-534,000 by the end of February, according to a new forecast by the CDC, which includes models from 36 national groups. Deaths will likely decrease during the next 4 weeks, with about 11,300-22,600 deaths possibly reported during the last week of February.

The 534,000 total would equal about 1 death for every minute of the pandemic, according to CNN, given that the first U.S. death was reported on Feb. 29 last year.

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

Patients who received telemedicine in an intensive care unit were less likely to die and more likely to have a shorter hospital stay than those who received standard ICU care without a 24-hour intensivist on-site, new data suggest.

Chiedozie I. Udeh, MD, staff intensivist with the Cleveland Clinic Foundation, presented results of a retrospective study of 153,987 consecutive ICU patients at the Critical Care Congress sponsored by the Society of Critical Care Medicine. .

Among the statistically significant findings were that 30-day mortality decreased by 18% (odds ratio, 0.82; 95% confidence interval, 0.77-0.87) and length of stay in the ICU decreased by 1.6 days in the telehealth model (95% CI, 1.5-1.7), compared with the traditional model. The total length of the average hospital stay was reduced by 2.1 days (95% CI, 1.9-2.4).

Patients in the study received ICU care at one of nine Cleveland Clinic hospitals between Jan. 1, 2010, and Dec. 31, 2019. Overall, 108,482 (70%) received ICU-telemedicine care during hours when an intensivist was not on-site.

Dr. Udeh said in an interview that only the largest academic centers typically have an intensivist on-site 24 hours a day. In the traditional model, critical care specialists may be on-site during the day but on call after hours.

In the tele-ICU model, in contrast, an intensivist – perhaps at a command center serving several hospitals – can observe and order treatments for patients remotely. The specialist has access to the patient’s medical record and test results, can monitor vital signs and visible changes, and can talk with both the patient and the nurse or other provider in the room.

Dr. Udeh said he suspects the 18% drop in mortality risk and the shorter hospital stay come from time saved. The physician doesn’t have to ask the nurse to look up health information and with constant monitoring can spot problems sooner or prevent them.

“You reduce a lot of the time from event to intervention or prevent an event by being more proactive,” Dr. Udeh said.

Ben Scott, MD, associate professor of anesthesiology and critical care at the University of Colorado at Denver, Aurora, said in an interview that his institution uses the tele-ICU model in several of the smaller hospitals there and is not surprised that Dr. Udeh’s team found such positive results. Dr. Scott was not involved in Dr. Udeh’s study.

“Most of us who have been working in this area and studying the results believe that these programs can make a big difference,” said Dr. Scott, vice chair for the SCCM tele-critical-care committee.

The smaller UC hospitals have ICU capability but not the census numbers to warrant 24-hour intensivist coverage. Of course, they do have 24-hour nursing coverage, and they typically use telemedicine when an intensivist is needed during the night, Dr. Scott said.
 

Hard to pinpoint telemedicine’s role

Dr. Scott said it’s hard to determine from studies how much telemedicine is influencing outcomes, compared with potentially confounding factors. A hospital with several ICUs might choose to send a patient to a certain ICU for a particular reason, which could confound comparisons.

The statistical techniques Dr. Udeh’s team used, however, helped account for confounding, Dr. Scott said. The extended years for the study and large patient sample also strengthen confidence in the results, he said.

The researchers found that several factors can increase an ICU patient’s risk of dying, including the reason for admission (such as cardiac arrest or sepsis), being admitted on a weekend, and the patient’s race. But they found that telemedicine might mitigate the effects of weekend admissions; the telemedicine patients admitted on a weekend in this study were no more likely to die than those admitted on a weekday.

The telemedicine model is especially important in areas without intensivists.

“If my only recourse is to send my patient out of town or out of state to another hospital, it’s a win-win,” Dr. Udeh said.

Regardless of the resources of individual hospitals, the national picture is clear, he said. “We just don’t have enough people trained in critical care to place an intensivist in every ICU 24/7.”

In late January, Santa Cruz Valley Regional Hospital in Green Valley, Ariz., temporarily shut down its ICU. The hospital CEO said the closure came because the hospital was unable to hire a pulmonologist.
 

Balancing cost issues

Cost issues with the tele-ICU have been a barrier for widespread adoption, Dr. Udeh said. He estimated that only about 15%-20% of hospitals incorporate the model.

Hospitals must pay for hardware and the telehealth service while still needing to have someone on staff available to come in if a physician’s presence is needed. And so far, those costs are not generally reimbursable by payers.

Hospitals must balance the costs with the potential for better outcomes and shorter stays, he said.

The model has benefits for the provider as well.

Dr. Udeh recounted being awakened by a call in the middle of the night and fighting off grogginess to quickly process information and make critical decisions.

But with the tele-ICU model, providers are awake for a specified shift and are periodically rounding on patients electronically with real-time access to health information.

Dr. Udeh said many of the tele-ICU platforms have decision support built in, with various degrees of complexity, so that the system might flag when a patient’s blood pressure is trending down, for example.

Although this research used prepandemic data, COVID-19 has highlighted the need for solutions to stretch ICU workforces.

Dr. Scott pointed out that in the pandemic, many hospitals that don’t have regular critical care services have had to take care of critically ill patients.

Having a telemedicine program can help bring that expertise to the bedside, he said.

Dr. Udeh, his coinvestigators, and Dr. Scott have disclosed no relevant financial relationships.

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

Patients who received telemedicine in an intensive care unit were less likely to die and more likely to have a shorter hospital stay than those who received standard ICU care without a 24-hour intensivist on-site, new data suggest.

Chiedozie I. Udeh, MD, staff intensivist with the Cleveland Clinic Foundation, presented results of a retrospective study of 153,987 consecutive ICU patients at the Critical Care Congress sponsored by the Society of Critical Care Medicine. .

Among the statistically significant findings were that 30-day mortality decreased by 18% (odds ratio, 0.82; 95% confidence interval, 0.77-0.87) and length of stay in the ICU decreased by 1.6 days in the telehealth model (95% CI, 1.5-1.7), compared with the traditional model. The total length of the average hospital stay was reduced by 2.1 days (95% CI, 1.9-2.4).

Patients in the study received ICU care at one of nine Cleveland Clinic hospitals between Jan. 1, 2010, and Dec. 31, 2019. Overall, 108,482 (70%) received ICU-telemedicine care during hours when an intensivist was not on-site.

Dr. Udeh said in an interview that only the largest academic centers typically have an intensivist on-site 24 hours a day. In the traditional model, critical care specialists may be on-site during the day but on call after hours.

In the tele-ICU model, in contrast, an intensivist – perhaps at a command center serving several hospitals – can observe and order treatments for patients remotely. The specialist has access to the patient’s medical record and test results, can monitor vital signs and visible changes, and can talk with both the patient and the nurse or other provider in the room.

Dr. Udeh said he suspects the 18% drop in mortality risk and the shorter hospital stay come from time saved. The physician doesn’t have to ask the nurse to look up health information and with constant monitoring can spot problems sooner or prevent them.

“You reduce a lot of the time from event to intervention or prevent an event by being more proactive,” Dr. Udeh said.

Ben Scott, MD, associate professor of anesthesiology and critical care at the University of Colorado at Denver, Aurora, said in an interview that his institution uses the tele-ICU model in several of the smaller hospitals there and is not surprised that Dr. Udeh’s team found such positive results. Dr. Scott was not involved in Dr. Udeh’s study.

“Most of us who have been working in this area and studying the results believe that these programs can make a big difference,” said Dr. Scott, vice chair for the SCCM tele-critical-care committee.

The smaller UC hospitals have ICU capability but not the census numbers to warrant 24-hour intensivist coverage. Of course, they do have 24-hour nursing coverage, and they typically use telemedicine when an intensivist is needed during the night, Dr. Scott said.
 

Hard to pinpoint telemedicine’s role

Dr. Scott said it’s hard to determine from studies how much telemedicine is influencing outcomes, compared with potentially confounding factors. A hospital with several ICUs might choose to send a patient to a certain ICU for a particular reason, which could confound comparisons.

The statistical techniques Dr. Udeh’s team used, however, helped account for confounding, Dr. Scott said. The extended years for the study and large patient sample also strengthen confidence in the results, he said.

The researchers found that several factors can increase an ICU patient’s risk of dying, including the reason for admission (such as cardiac arrest or sepsis), being admitted on a weekend, and the patient’s race. But they found that telemedicine might mitigate the effects of weekend admissions; the telemedicine patients admitted on a weekend in this study were no more likely to die than those admitted on a weekday.

The telemedicine model is especially important in areas without intensivists.

“If my only recourse is to send my patient out of town or out of state to another hospital, it’s a win-win,” Dr. Udeh said.

Regardless of the resources of individual hospitals, the national picture is clear, he said. “We just don’t have enough people trained in critical care to place an intensivist in every ICU 24/7.”

In late January, Santa Cruz Valley Regional Hospital in Green Valley, Ariz., temporarily shut down its ICU. The hospital CEO said the closure came because the hospital was unable to hire a pulmonologist.
 

Balancing cost issues

Cost issues with the tele-ICU have been a barrier for widespread adoption, Dr. Udeh said. He estimated that only about 15%-20% of hospitals incorporate the model.

Hospitals must pay for hardware and the telehealth service while still needing to have someone on staff available to come in if a physician’s presence is needed. And so far, those costs are not generally reimbursable by payers.

Hospitals must balance the costs with the potential for better outcomes and shorter stays, he said.

The model has benefits for the provider as well.

Dr. Udeh recounted being awakened by a call in the middle of the night and fighting off grogginess to quickly process information and make critical decisions.

But with the tele-ICU model, providers are awake for a specified shift and are periodically rounding on patients electronically with real-time access to health information.

Dr. Udeh said many of the tele-ICU platforms have decision support built in, with various degrees of complexity, so that the system might flag when a patient’s blood pressure is trending down, for example.

Although this research used prepandemic data, COVID-19 has highlighted the need for solutions to stretch ICU workforces.

Dr. Scott pointed out that in the pandemic, many hospitals that don’t have regular critical care services have had to take care of critically ill patients.

Having a telemedicine program can help bring that expertise to the bedside, he said.

Dr. Udeh, his coinvestigators, and Dr. Scott have disclosed no relevant financial relationships.

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

Patients who received telemedicine in an intensive care unit were less likely to die and more likely to have a shorter hospital stay than those who received standard ICU care without a 24-hour intensivist on-site, new data suggest.

Chiedozie I. Udeh, MD, staff intensivist with the Cleveland Clinic Foundation, presented results of a retrospective study of 153,987 consecutive ICU patients at the Critical Care Congress sponsored by the Society of Critical Care Medicine. .

Among the statistically significant findings were that 30-day mortality decreased by 18% (odds ratio, 0.82; 95% confidence interval, 0.77-0.87) and length of stay in the ICU decreased by 1.6 days in the telehealth model (95% CI, 1.5-1.7), compared with the traditional model. The total length of the average hospital stay was reduced by 2.1 days (95% CI, 1.9-2.4).

Patients in the study received ICU care at one of nine Cleveland Clinic hospitals between Jan. 1, 2010, and Dec. 31, 2019. Overall, 108,482 (70%) received ICU-telemedicine care during hours when an intensivist was not on-site.

Dr. Udeh said in an interview that only the largest academic centers typically have an intensivist on-site 24 hours a day. In the traditional model, critical care specialists may be on-site during the day but on call after hours.

In the tele-ICU model, in contrast, an intensivist – perhaps at a command center serving several hospitals – can observe and order treatments for patients remotely. The specialist has access to the patient’s medical record and test results, can monitor vital signs and visible changes, and can talk with both the patient and the nurse or other provider in the room.

Dr. Udeh said he suspects the 18% drop in mortality risk and the shorter hospital stay come from time saved. The physician doesn’t have to ask the nurse to look up health information and with constant monitoring can spot problems sooner or prevent them.

“You reduce a lot of the time from event to intervention or prevent an event by being more proactive,” Dr. Udeh said.

Ben Scott, MD, associate professor of anesthesiology and critical care at the University of Colorado at Denver, Aurora, said in an interview that his institution uses the tele-ICU model in several of the smaller hospitals there and is not surprised that Dr. Udeh’s team found such positive results. Dr. Scott was not involved in Dr. Udeh’s study.

“Most of us who have been working in this area and studying the results believe that these programs can make a big difference,” said Dr. Scott, vice chair for the SCCM tele-critical-care committee.

The smaller UC hospitals have ICU capability but not the census numbers to warrant 24-hour intensivist coverage. Of course, they do have 24-hour nursing coverage, and they typically use telemedicine when an intensivist is needed during the night, Dr. Scott said.
 

Hard to pinpoint telemedicine’s role

Dr. Scott said it’s hard to determine from studies how much telemedicine is influencing outcomes, compared with potentially confounding factors. A hospital with several ICUs might choose to send a patient to a certain ICU for a particular reason, which could confound comparisons.

The statistical techniques Dr. Udeh’s team used, however, helped account for confounding, Dr. Scott said. The extended years for the study and large patient sample also strengthen confidence in the results, he said.

The researchers found that several factors can increase an ICU patient’s risk of dying, including the reason for admission (such as cardiac arrest or sepsis), being admitted on a weekend, and the patient’s race. But they found that telemedicine might mitigate the effects of weekend admissions; the telemedicine patients admitted on a weekend in this study were no more likely to die than those admitted on a weekday.

The telemedicine model is especially important in areas without intensivists.

“If my only recourse is to send my patient out of town or out of state to another hospital, it’s a win-win,” Dr. Udeh said.

Regardless of the resources of individual hospitals, the national picture is clear, he said. “We just don’t have enough people trained in critical care to place an intensivist in every ICU 24/7.”

In late January, Santa Cruz Valley Regional Hospital in Green Valley, Ariz., temporarily shut down its ICU. The hospital CEO said the closure came because the hospital was unable to hire a pulmonologist.
 

Balancing cost issues

Cost issues with the tele-ICU have been a barrier for widespread adoption, Dr. Udeh said. He estimated that only about 15%-20% of hospitals incorporate the model.

Hospitals must pay for hardware and the telehealth service while still needing to have someone on staff available to come in if a physician’s presence is needed. And so far, those costs are not generally reimbursable by payers.

Hospitals must balance the costs with the potential for better outcomes and shorter stays, he said.

The model has benefits for the provider as well.

Dr. Udeh recounted being awakened by a call in the middle of the night and fighting off grogginess to quickly process information and make critical decisions.

But with the tele-ICU model, providers are awake for a specified shift and are periodically rounding on patients electronically with real-time access to health information.

Dr. Udeh said many of the tele-ICU platforms have decision support built in, with various degrees of complexity, so that the system might flag when a patient’s blood pressure is trending down, for example.

Although this research used prepandemic data, COVID-19 has highlighted the need for solutions to stretch ICU workforces.

Dr. Scott pointed out that in the pandemic, many hospitals that don’t have regular critical care services have had to take care of critically ill patients.

Having a telemedicine program can help bring that expertise to the bedside, he said.

Dr. Udeh, his coinvestigators, and Dr. Scott have disclosed no relevant financial relationships.

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

The final numbers won’t look much different, but the 2021 Match results will be unlike any before. As of mid-January, only 16 more institutions were confirmed to be participating in Match Day this year, resulting in about 800 more positions, said Donna Lamb, president and CEO of the National Resident Matching Program (NRMP). The Electronic Residency Application Service reported about 50,000 individual applicant submissions, a slight increase from prior years.

The stats may be similar, but the current residency application cycle may lead to wildly different results after the pandemic forced interviews to be conducted virtually and caused the cancellation of most away clinical rotations. Troy Amen, a fifth-year MD-MBA student at Harvard Medical School, Boston, and copresident of his student class, says the lack of on-campus, in-person experiences means students feel more in the dark than ever. The same is true for institutions. “The programs are also suffering because now they don’t know which students are a good ‘cultural fit’ for them,” he said.

Standing out has always been a concern for prospective residents, but Mr. Amen says fears are even higher this year. “[Institutions are] struggling to vet out 850 applicants, and they have no connection to us.”

Organizations have scrambled to keep the process as fair and informative as possible. “Everyone is trying to do the right thing here,” said Alison J. Whelan, MD, chief academic officer of the Association of American Medical Colleges (AAMC). She says that although the process has significantly changed, the heart of it remains the same. “The bottom line is directors really want to fill their intern class, and schools and students really want to match.”

Since the NRMP was established in 1952, it has never had to contend with a pandemic of this scale. The unprecedented circumstances have led to some much-feared and some unexpected changes, like top candidates “stealing” interview slots, “swag bags” sent to entice residents, beefed-up online profiles, as well as “Zoom fatigue,” a spike in home-field advantage for institutions, and massive anxiety for those students staking their future to a city they may have never seen in person.
 

What was lost and what was gained

“It’s really hard to get a real feel for the program when you’ve not been there in person,” said Christopher Smith, MD, director of the internal medicine residency program at Beth Israel Deaconess Medical Center in Boston. Dr. Smith recalled interviewing for residencies 25 years ago. His wife, a teacher, took time off to travel with him.

“She would ‘interview the town’ while I interviewed the program, and we compared notes at night,” he said. Because of COVID-19-related travel restrictions, just physically seeing the city in which they may live for years wasn’t an option for many. “I have a lot of sympathy for students applying right now,” Dr. Smith said.

For the residency class of 2021, the first shoe really dropped last March, when the AAMC issued guidance strongly recommending that programs pause clinical rotations away from their home schools. As established doctors know well, and as graduating medical students confirmed, these rotations are crucial to understanding a program’s culture and gaining experience that can boost candidacy. “I’m applying to orthopedic surgery, where away rotations are the gold standard for impressing attendees and residents at institutions away from home,” said Mr. Amen.

The pandemic completely cut off that key source of information to determine the right fit. It also meant applicants couldn’t have as diverse a portfolio of recommendation letters, something many worry may be detrimental to their soon-to-be-released Match rankings.

Unlike the loss of away rotations, the forced shift from in-person to virtual interviews had some meaningful benefits. Students no longer incurred expenses for airline flights, hotel rooms, and rental cars. Many organizations and programs have been trying for years to figure out how to lower the financial burden of interviews to make the process more equitable for those at economic or other disadvantage.

“The equity piece of this is huge – decreasing barriers and leveling the field a little bit is a really huge advantage,” said Kate Shaw, MD, residency program director and associate chair of education for the obstetrics and gynecology program at Stanford (Calif.) University. In some ways, this latest change is an extension of a strategy Dr. Shaw and others had already begun implementing.

“Over the last 5 to 10 years, we’ve been working to address the implicit bias in the application process, so we’ve gone to a holistic review of applicants, where we don’t have score cutoffs. We look at the whole person,” she said. “And we did that in an effort to increase diversity and equity.” Dr. Shaw and others hope that the accidental positive changes from COVID restrictions may be intentionally preserved long after the pandemic ends.
 

Home-field advantage vs. swag bags

Many medical students applying to residencies this year say they have given greater weight to their home programs than they might have without the pandemic. “I didn’t get a sense of anyone’s culture other than my home institution,” said Alex Skidmore, a fourth-year medical student at Washington University in St. Louis. “I definitely am ranking Wash-U higher.”

The desire to emphasize the known quality of a student’s home institution isn’t surprising to program directors. Dr. Shaw said she thinks this year’s Match could well end with a higher percentage of students matching either in their home programs or in programs close to loved ones. “The value of being close to family has come up in our conversations, where students are considering the right program for them but also the other life factors,” she said.

To overcome this home-field advantage, many programs have beefed up their websites, including providing video tours of their facilities. They also “upped their social media game” and encouraged residents to create online groups for prospective residents to share information about programs and life outside of work. Some residents even offered video tours of their personal apartments to applicants.

Without in-person access to facilities and staff, a program’s online presence became a deciding factor, applicants said. “If you have a bad website, it’s like having a dirty building to interview applicants in,” Mr. Skidmore said. For many prospective residents, an institution’s Internet presence was a “make or break” factor. “It’s the only thing I saw for many programs, and when we are doing the amount of research we are doing remotely, when I saw a program with a bad website, it made me not like the program as much,” he said.

Some programs, hoping to woo candidates as well as to provide them with more insight into what they and their cities have to offer, sent “swag bags” to candidates. These included things like gift cards for food delivery and offerings from local businesses. Washington University’s pediatrics residency program sent gooey butter cakes – a St. Louis staple – along with other treats from small businesses and copies of magazines that showcased the city’s dining and entertainment scene.

Other programs, even those at the same medical institution, felt quite strongly that those types of packages shouldn’t be sent. “We interviewed almost 500 applicants, so there was no way we could have afforded that,” said Dominique Cosco, MD, director of Washington University’s internal medicine residency program. “Our normal recruitment budget is almost $100,000 in a normal year, and that got cut because of COVID. For us, it was thinking about allocations of resources.”
 

Interview slot theft and zoom fatigue

Remote interviewing also meant that applicants could accept more interviews, something that raised a big concern. Without expenses or travel time, would top-tier candidates take more interviews than normal and thus take limited interview spots from other qualified candidates? Maybe so, says the AAMC’s Dr. Whelan.

“We didn’t have systematic data, but we heard from enough schools and programs ... that students who were maybe not the top-top ranked students in the class but in every way solid were receiving fewer interviews than previous years,” Dr. Whelan said. This is despite guidance that recommended programs add interview slots to serve as a counterbalance.

Some students say they accepted more interview slots in the beginning of the interview season, partly because they could, and partly because some thought of early interviews as “practice” for later interviews. However, as video interviews piled up, some of them described feeling “Zoom fatigue” and said they later canceled interviews with programs they didn’t anticipate joining.
 

More SOAP, less clarity

As for what comes next, the NRMP is preparing for a longer-than-normal Supplemental Offer and Acceptance Program (SOAP) than in years past. SOAP usually offers three rounds of matches after the initial Match Day; Ms. Lamb said things are different this year.

“SOAP will be the same number of days, but we’ve added an additional round on Thursday afternoon,” she said. Will it be unnecessary or not enough? Nobody knows. “How big SOAP actually is going to be is one of the things that we really don’t have a sense of right now and probably aren’t going to have a sense of until the Match.”

Uncertainty is the name of the game. More than any other Match before, programs and applicants won’t know how results from this pandemic year stack up for a few months at the very least. “I really want to see what this looks like on the other side,” Dr. Smith said. “Are applicants happy with the way it looks when they come here? Do they feel like they matched with the right place?”

Whether this unprecedented year will be remembered more for positive changes moving forward, including more flexibility on remote interviews, or for less-informed decisions that result in dissatisfied participants is also unclear.

“I think after the Match is over, we’ll be talking to everyone to get more perspective on what people who are applying now would tell the next class, and how programs can adjust,” said Kathy Diemer, MD, assistant dean for career counseling at Washington University. At the very least, those who are involved in this year after year can start thinking about what the future should look like.

“We’re going to need to do some kind of debriefing after this is over, both program directors and our students as well, so we can determine how to move forward next year and beyond.”

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

The final numbers won’t look much different, but the 2021 Match results will be unlike any before. As of mid-January, only 16 more institutions were confirmed to be participating in Match Day this year, resulting in about 800 more positions, said Donna Lamb, president and CEO of the National Resident Matching Program (NRMP). The Electronic Residency Application Service reported about 50,000 individual applicant submissions, a slight increase from prior years.

The stats may be similar, but the current residency application cycle may lead to wildly different results after the pandemic forced interviews to be conducted virtually and caused the cancellation of most away clinical rotations. Troy Amen, a fifth-year MD-MBA student at Harvard Medical School, Boston, and copresident of his student class, says the lack of on-campus, in-person experiences means students feel more in the dark than ever. The same is true for institutions. “The programs are also suffering because now they don’t know which students are a good ‘cultural fit’ for them,” he said.

Standing out has always been a concern for prospective residents, but Mr. Amen says fears are even higher this year. “[Institutions are] struggling to vet out 850 applicants, and they have no connection to us.”

Organizations have scrambled to keep the process as fair and informative as possible. “Everyone is trying to do the right thing here,” said Alison J. Whelan, MD, chief academic officer of the Association of American Medical Colleges (AAMC). She says that although the process has significantly changed, the heart of it remains the same. “The bottom line is directors really want to fill their intern class, and schools and students really want to match.”

Since the NRMP was established in 1952, it has never had to contend with a pandemic of this scale. The unprecedented circumstances have led to some much-feared and some unexpected changes, like top candidates “stealing” interview slots, “swag bags” sent to entice residents, beefed-up online profiles, as well as “Zoom fatigue,” a spike in home-field advantage for institutions, and massive anxiety for those students staking their future to a city they may have never seen in person.
 

What was lost and what was gained

“It’s really hard to get a real feel for the program when you’ve not been there in person,” said Christopher Smith, MD, director of the internal medicine residency program at Beth Israel Deaconess Medical Center in Boston. Dr. Smith recalled interviewing for residencies 25 years ago. His wife, a teacher, took time off to travel with him.

“She would ‘interview the town’ while I interviewed the program, and we compared notes at night,” he said. Because of COVID-19-related travel restrictions, just physically seeing the city in which they may live for years wasn’t an option for many. “I have a lot of sympathy for students applying right now,” Dr. Smith said.

For the residency class of 2021, the first shoe really dropped last March, when the AAMC issued guidance strongly recommending that programs pause clinical rotations away from their home schools. As established doctors know well, and as graduating medical students confirmed, these rotations are crucial to understanding a program’s culture and gaining experience that can boost candidacy. “I’m applying to orthopedic surgery, where away rotations are the gold standard for impressing attendees and residents at institutions away from home,” said Mr. Amen.

The pandemic completely cut off that key source of information to determine the right fit. It also meant applicants couldn’t have as diverse a portfolio of recommendation letters, something many worry may be detrimental to their soon-to-be-released Match rankings.

Unlike the loss of away rotations, the forced shift from in-person to virtual interviews had some meaningful benefits. Students no longer incurred expenses for airline flights, hotel rooms, and rental cars. Many organizations and programs have been trying for years to figure out how to lower the financial burden of interviews to make the process more equitable for those at economic or other disadvantage.

“The equity piece of this is huge – decreasing barriers and leveling the field a little bit is a really huge advantage,” said Kate Shaw, MD, residency program director and associate chair of education for the obstetrics and gynecology program at Stanford (Calif.) University. In some ways, this latest change is an extension of a strategy Dr. Shaw and others had already begun implementing.

“Over the last 5 to 10 years, we’ve been working to address the implicit bias in the application process, so we’ve gone to a holistic review of applicants, where we don’t have score cutoffs. We look at the whole person,” she said. “And we did that in an effort to increase diversity and equity.” Dr. Shaw and others hope that the accidental positive changes from COVID restrictions may be intentionally preserved long after the pandemic ends.
 

Home-field advantage vs. swag bags

Many medical students applying to residencies this year say they have given greater weight to their home programs than they might have without the pandemic. “I didn’t get a sense of anyone’s culture other than my home institution,” said Alex Skidmore, a fourth-year medical student at Washington University in St. Louis. “I definitely am ranking Wash-U higher.”

The desire to emphasize the known quality of a student’s home institution isn’t surprising to program directors. Dr. Shaw said she thinks this year’s Match could well end with a higher percentage of students matching either in their home programs or in programs close to loved ones. “The value of being close to family has come up in our conversations, where students are considering the right program for them but also the other life factors,” she said.

To overcome this home-field advantage, many programs have beefed up their websites, including providing video tours of their facilities. They also “upped their social media game” and encouraged residents to create online groups for prospective residents to share information about programs and life outside of work. Some residents even offered video tours of their personal apartments to applicants.

Without in-person access to facilities and staff, a program’s online presence became a deciding factor, applicants said. “If you have a bad website, it’s like having a dirty building to interview applicants in,” Mr. Skidmore said. For many prospective residents, an institution’s Internet presence was a “make or break” factor. “It’s the only thing I saw for many programs, and when we are doing the amount of research we are doing remotely, when I saw a program with a bad website, it made me not like the program as much,” he said.

Some programs, hoping to woo candidates as well as to provide them with more insight into what they and their cities have to offer, sent “swag bags” to candidates. These included things like gift cards for food delivery and offerings from local businesses. Washington University’s pediatrics residency program sent gooey butter cakes – a St. Louis staple – along with other treats from small businesses and copies of magazines that showcased the city’s dining and entertainment scene.

Other programs, even those at the same medical institution, felt quite strongly that those types of packages shouldn’t be sent. “We interviewed almost 500 applicants, so there was no way we could have afforded that,” said Dominique Cosco, MD, director of Washington University’s internal medicine residency program. “Our normal recruitment budget is almost $100,000 in a normal year, and that got cut because of COVID. For us, it was thinking about allocations of resources.”
 

Interview slot theft and zoom fatigue

Remote interviewing also meant that applicants could accept more interviews, something that raised a big concern. Without expenses or travel time, would top-tier candidates take more interviews than normal and thus take limited interview spots from other qualified candidates? Maybe so, says the AAMC’s Dr. Whelan.

“We didn’t have systematic data, but we heard from enough schools and programs ... that students who were maybe not the top-top ranked students in the class but in every way solid were receiving fewer interviews than previous years,” Dr. Whelan said. This is despite guidance that recommended programs add interview slots to serve as a counterbalance.

Some students say they accepted more interview slots in the beginning of the interview season, partly because they could, and partly because some thought of early interviews as “practice” for later interviews. However, as video interviews piled up, some of them described feeling “Zoom fatigue” and said they later canceled interviews with programs they didn’t anticipate joining.
 

More SOAP, less clarity

As for what comes next, the NRMP is preparing for a longer-than-normal Supplemental Offer and Acceptance Program (SOAP) than in years past. SOAP usually offers three rounds of matches after the initial Match Day; Ms. Lamb said things are different this year.

“SOAP will be the same number of days, but we’ve added an additional round on Thursday afternoon,” she said. Will it be unnecessary or not enough? Nobody knows. “How big SOAP actually is going to be is one of the things that we really don’t have a sense of right now and probably aren’t going to have a sense of until the Match.”

Uncertainty is the name of the game. More than any other Match before, programs and applicants won’t know how results from this pandemic year stack up for a few months at the very least. “I really want to see what this looks like on the other side,” Dr. Smith said. “Are applicants happy with the way it looks when they come here? Do they feel like they matched with the right place?”

Whether this unprecedented year will be remembered more for positive changes moving forward, including more flexibility on remote interviews, or for less-informed decisions that result in dissatisfied participants is also unclear.

“I think after the Match is over, we’ll be talking to everyone to get more perspective on what people who are applying now would tell the next class, and how programs can adjust,” said Kathy Diemer, MD, assistant dean for career counseling at Washington University. At the very least, those who are involved in this year after year can start thinking about what the future should look like.

“We’re going to need to do some kind of debriefing after this is over, both program directors and our students as well, so we can determine how to move forward next year and beyond.”

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

The final numbers won’t look much different, but the 2021 Match results will be unlike any before. As of mid-January, only 16 more institutions were confirmed to be participating in Match Day this year, resulting in about 800 more positions, said Donna Lamb, president and CEO of the National Resident Matching Program (NRMP). The Electronic Residency Application Service reported about 50,000 individual applicant submissions, a slight increase from prior years.

The stats may be similar, but the current residency application cycle may lead to wildly different results after the pandemic forced interviews to be conducted virtually and caused the cancellation of most away clinical rotations. Troy Amen, a fifth-year MD-MBA student at Harvard Medical School, Boston, and copresident of his student class, says the lack of on-campus, in-person experiences means students feel more in the dark than ever. The same is true for institutions. “The programs are also suffering because now they don’t know which students are a good ‘cultural fit’ for them,” he said.

Standing out has always been a concern for prospective residents, but Mr. Amen says fears are even higher this year. “[Institutions are] struggling to vet out 850 applicants, and they have no connection to us.”

Organizations have scrambled to keep the process as fair and informative as possible. “Everyone is trying to do the right thing here,” said Alison J. Whelan, MD, chief academic officer of the Association of American Medical Colleges (AAMC). She says that although the process has significantly changed, the heart of it remains the same. “The bottom line is directors really want to fill their intern class, and schools and students really want to match.”

Since the NRMP was established in 1952, it has never had to contend with a pandemic of this scale. The unprecedented circumstances have led to some much-feared and some unexpected changes, like top candidates “stealing” interview slots, “swag bags” sent to entice residents, beefed-up online profiles, as well as “Zoom fatigue,” a spike in home-field advantage for institutions, and massive anxiety for those students staking their future to a city they may have never seen in person.
 

What was lost and what was gained

“It’s really hard to get a real feel for the program when you’ve not been there in person,” said Christopher Smith, MD, director of the internal medicine residency program at Beth Israel Deaconess Medical Center in Boston. Dr. Smith recalled interviewing for residencies 25 years ago. His wife, a teacher, took time off to travel with him.

“She would ‘interview the town’ while I interviewed the program, and we compared notes at night,” he said. Because of COVID-19-related travel restrictions, just physically seeing the city in which they may live for years wasn’t an option for many. “I have a lot of sympathy for students applying right now,” Dr. Smith said.

For the residency class of 2021, the first shoe really dropped last March, when the AAMC issued guidance strongly recommending that programs pause clinical rotations away from their home schools. As established doctors know well, and as graduating medical students confirmed, these rotations are crucial to understanding a program’s culture and gaining experience that can boost candidacy. “I’m applying to orthopedic surgery, where away rotations are the gold standard for impressing attendees and residents at institutions away from home,” said Mr. Amen.

The pandemic completely cut off that key source of information to determine the right fit. It also meant applicants couldn’t have as diverse a portfolio of recommendation letters, something many worry may be detrimental to their soon-to-be-released Match rankings.

Unlike the loss of away rotations, the forced shift from in-person to virtual interviews had some meaningful benefits. Students no longer incurred expenses for airline flights, hotel rooms, and rental cars. Many organizations and programs have been trying for years to figure out how to lower the financial burden of interviews to make the process more equitable for those at economic or other disadvantage.

“The equity piece of this is huge – decreasing barriers and leveling the field a little bit is a really huge advantage,” said Kate Shaw, MD, residency program director and associate chair of education for the obstetrics and gynecology program at Stanford (Calif.) University. In some ways, this latest change is an extension of a strategy Dr. Shaw and others had already begun implementing.

“Over the last 5 to 10 years, we’ve been working to address the implicit bias in the application process, so we’ve gone to a holistic review of applicants, where we don’t have score cutoffs. We look at the whole person,” she said. “And we did that in an effort to increase diversity and equity.” Dr. Shaw and others hope that the accidental positive changes from COVID restrictions may be intentionally preserved long after the pandemic ends.
 

Home-field advantage vs. swag bags

Many medical students applying to residencies this year say they have given greater weight to their home programs than they might have without the pandemic. “I didn’t get a sense of anyone’s culture other than my home institution,” said Alex Skidmore, a fourth-year medical student at Washington University in St. Louis. “I definitely am ranking Wash-U higher.”

The desire to emphasize the known quality of a student’s home institution isn’t surprising to program directors. Dr. Shaw said she thinks this year’s Match could well end with a higher percentage of students matching either in their home programs or in programs close to loved ones. “The value of being close to family has come up in our conversations, where students are considering the right program for them but also the other life factors,” she said.

To overcome this home-field advantage, many programs have beefed up their websites, including providing video tours of their facilities. They also “upped their social media game” and encouraged residents to create online groups for prospective residents to share information about programs and life outside of work. Some residents even offered video tours of their personal apartments to applicants.

Without in-person access to facilities and staff, a program’s online presence became a deciding factor, applicants said. “If you have a bad website, it’s like having a dirty building to interview applicants in,” Mr. Skidmore said. For many prospective residents, an institution’s Internet presence was a “make or break” factor. “It’s the only thing I saw for many programs, and when we are doing the amount of research we are doing remotely, when I saw a program with a bad website, it made me not like the program as much,” he said.

Some programs, hoping to woo candidates as well as to provide them with more insight into what they and their cities have to offer, sent “swag bags” to candidates. These included things like gift cards for food delivery and offerings from local businesses. Washington University’s pediatrics residency program sent gooey butter cakes – a St. Louis staple – along with other treats from small businesses and copies of magazines that showcased the city’s dining and entertainment scene.

Other programs, even those at the same medical institution, felt quite strongly that those types of packages shouldn’t be sent. “We interviewed almost 500 applicants, so there was no way we could have afforded that,” said Dominique Cosco, MD, director of Washington University’s internal medicine residency program. “Our normal recruitment budget is almost $100,000 in a normal year, and that got cut because of COVID. For us, it was thinking about allocations of resources.”
 

Interview slot theft and zoom fatigue

Remote interviewing also meant that applicants could accept more interviews, something that raised a big concern. Without expenses or travel time, would top-tier candidates take more interviews than normal and thus take limited interview spots from other qualified candidates? Maybe so, says the AAMC’s Dr. Whelan.

“We didn’t have systematic data, but we heard from enough schools and programs ... that students who were maybe not the top-top ranked students in the class but in every way solid were receiving fewer interviews than previous years,” Dr. Whelan said. This is despite guidance that recommended programs add interview slots to serve as a counterbalance.

Some students say they accepted more interview slots in the beginning of the interview season, partly because they could, and partly because some thought of early interviews as “practice” for later interviews. However, as video interviews piled up, some of them described feeling “Zoom fatigue” and said they later canceled interviews with programs they didn’t anticipate joining.
 

More SOAP, less clarity

As for what comes next, the NRMP is preparing for a longer-than-normal Supplemental Offer and Acceptance Program (SOAP) than in years past. SOAP usually offers three rounds of matches after the initial Match Day; Ms. Lamb said things are different this year.

“SOAP will be the same number of days, but we’ve added an additional round on Thursday afternoon,” she said. Will it be unnecessary or not enough? Nobody knows. “How big SOAP actually is going to be is one of the things that we really don’t have a sense of right now and probably aren’t going to have a sense of until the Match.”

Uncertainty is the name of the game. More than any other Match before, programs and applicants won’t know how results from this pandemic year stack up for a few months at the very least. “I really want to see what this looks like on the other side,” Dr. Smith said. “Are applicants happy with the way it looks when they come here? Do they feel like they matched with the right place?”

Whether this unprecedented year will be remembered more for positive changes moving forward, including more flexibility on remote interviews, or for less-informed decisions that result in dissatisfied participants is also unclear.

“I think after the Match is over, we’ll be talking to everyone to get more perspective on what people who are applying now would tell the next class, and how programs can adjust,” said Kathy Diemer, MD, assistant dean for career counseling at Washington University. At the very least, those who are involved in this year after year can start thinking about what the future should look like.

“We’re going to need to do some kind of debriefing after this is over, both program directors and our students as well, so we can determine how to move forward next year and beyond.”

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

A third of patients with COVID-19 and thoracic malignancies die, according to updated results from the TERAVOLT registry.

The risk of death was similar across racial and ethnic groups. Factors associated with an increased risk of death were male sex, older age, worse performance scores, and four or more metastatic sites.

“Death rates remain high at 33%, underscoring the importance of COVID-19 vaccination in patients with thoracic cancers, when available,” said Umit Tapan, MD, of Boston University.

Dr. Tapan presented the TERAVOLT update at the 2020 World Congress on Lung Cancer (Abstract P09.18), which was rescheduled for January 2021.

The TERAVOLT registry is a multicenter, observational study with a cross-sectional component and a longitudinal cohort component.

The registry includes patients who have thoracic cancers – non–small cell lung cancer (NSCLC), small cell lung cancer, mesothelioma, thymic epithelial tumors, and other pulmonary neuroendocrine neoplasms – and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms.

Clinical data were extracted from medical records of consecutive patients from Jan. 1, 2020, and will be collected until the end of pandemic, as declared by the World Health Organization. Data collected include demographics, oncologic history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes.

“The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus,” Dr. Tapan said.

Data from TERAVOLT were previously presented at AACR, ASCO, and ESMO last year, as well as published in The Lancet Oncology.

Updated results

Dr. Tapan presented data on 1,011 patients from 120 centers in 19 countries. The patients’ median age was 68 years (range, 28-95 years), and more than half were male (58%). Most patients (72%) were White, 20% were Hispanic/Latino, and 8% were Black/African American.

Most patients had NSCLC (82%), and most had stage IV disease (68%). Patients had received a median of one prior line of therapy.

As in earlier reports of TERAVOLT data, the mortality rate was 33%.

In a multivariate analysis, the following characteristics were associated with an increased risk of death:

• Male sex (odds ratio, 1.4).
• Older age (per 10 years; OR, 1.21).
• Performance score of 1 (OR, 1.73), 2 (OR, 4.74), and 3/4 (OR, 10.7).
• Four or more metastatic sites (OR, 3.05).

The following characteristics were associated with an increased risk of hospitalization in a multivariate analysis:

• Male sex (OR, 1.67).
• Older age (per 10 years; OR, 1.24).
• Performance score of 2 (OR, 4.47) and 3/4 (OR, 9.63).
• Four or more metastatic sites (OR, 4.0).
• Thymic carcinoma (OR, 3.58).
• Receiving radiation (OR, 2.1).

Race and ethnicity did not seem to affect the risk of death or hospitalization, “but we plan to conduct further analysis,” Dr. Tapan said.

Roxana Reyes, MD, of Hospital Clínic de Barcelona, said her hospital sees patients with lung cancer at high risk for COVID-19, but there is no screening program in place.

“We use medical consultations to focus on early diagnosis. We treat COVID-19 complications but lose a lot of patients. There is an opportunity to be found to find these patients sooner,” Dr. Reyes said.

She noted that COVID-19 will likely last a long time, and therefore “we have to protect against it and continue to diagnose lung cancer at earlier stages.”

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. Dr. Tapan has no relevant disclosures. The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer.

A third of patients with COVID-19 and thoracic malignancies die, according to updated results from the TERAVOLT registry.

The risk of death was similar across racial and ethnic groups. Factors associated with an increased risk of death were male sex, older age, worse performance scores, and four or more metastatic sites.

“Death rates remain high at 33%, underscoring the importance of COVID-19 vaccination in patients with thoracic cancers, when available,” said Umit Tapan, MD, of Boston University.

Dr. Tapan presented the TERAVOLT update at the 2020 World Congress on Lung Cancer (Abstract P09.18), which was rescheduled for January 2021.

The TERAVOLT registry is a multicenter, observational study with a cross-sectional component and a longitudinal cohort component.

The registry includes patients who have thoracic cancers – non–small cell lung cancer (NSCLC), small cell lung cancer, mesothelioma, thymic epithelial tumors, and other pulmonary neuroendocrine neoplasms – and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms.

Clinical data were extracted from medical records of consecutive patients from Jan. 1, 2020, and will be collected until the end of pandemic, as declared by the World Health Organization. Data collected include demographics, oncologic history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes.

“The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus,” Dr. Tapan said.

Data from TERAVOLT were previously presented at AACR, ASCO, and ESMO last year, as well as published in The Lancet Oncology.

Updated results

Dr. Tapan presented data on 1,011 patients from 120 centers in 19 countries. The patients’ median age was 68 years (range, 28-95 years), and more than half were male (58%). Most patients (72%) were White, 20% were Hispanic/Latino, and 8% were Black/African American.

Most patients had NSCLC (82%), and most had stage IV disease (68%). Patients had received a median of one prior line of therapy.

As in earlier reports of TERAVOLT data, the mortality rate was 33%.

In a multivariate analysis, the following characteristics were associated with an increased risk of death:

• Male sex (odds ratio, 1.4).
• Older age (per 10 years; OR, 1.21).
• Performance score of 1 (OR, 1.73), 2 (OR, 4.74), and 3/4 (OR, 10.7).
• Four or more metastatic sites (OR, 3.05).

The following characteristics were associated with an increased risk of hospitalization in a multivariate analysis:

• Male sex (OR, 1.67).
• Older age (per 10 years; OR, 1.24).
• Performance score of 2 (OR, 4.47) and 3/4 (OR, 9.63).
• Four or more metastatic sites (OR, 4.0).
• Thymic carcinoma (OR, 3.58).
• Receiving radiation (OR, 2.1).

Race and ethnicity did not seem to affect the risk of death or hospitalization, “but we plan to conduct further analysis,” Dr. Tapan said.

Roxana Reyes, MD, of Hospital Clínic de Barcelona, said her hospital sees patients with lung cancer at high risk for COVID-19, but there is no screening program in place.

“We use medical consultations to focus on early diagnosis. We treat COVID-19 complications but lose a lot of patients. There is an opportunity to be found to find these patients sooner,” Dr. Reyes said.

She noted that COVID-19 will likely last a long time, and therefore “we have to protect against it and continue to diagnose lung cancer at earlier stages.”

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. Dr. Tapan has no relevant disclosures. The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer.

A third of patients with COVID-19 and thoracic malignancies die, according to updated results from the TERAVOLT registry.

The risk of death was similar across racial and ethnic groups. Factors associated with an increased risk of death were male sex, older age, worse performance scores, and four or more metastatic sites.

“Death rates remain high at 33%, underscoring the importance of COVID-19 vaccination in patients with thoracic cancers, when available,” said Umit Tapan, MD, of Boston University.

Dr. Tapan presented the TERAVOLT update at the 2020 World Congress on Lung Cancer (Abstract P09.18), which was rescheduled for January 2021.

The TERAVOLT registry is a multicenter, observational study with a cross-sectional component and a longitudinal cohort component.

The registry includes patients who have thoracic cancers – non–small cell lung cancer (NSCLC), small cell lung cancer, mesothelioma, thymic epithelial tumors, and other pulmonary neuroendocrine neoplasms – and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms.

Clinical data were extracted from medical records of consecutive patients from Jan. 1, 2020, and will be collected until the end of pandemic, as declared by the World Health Organization. Data collected include demographics, oncologic history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes.

“The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus,” Dr. Tapan said.

Data from TERAVOLT were previously presented at AACR, ASCO, and ESMO last year, as well as published in The Lancet Oncology.

Updated results

Dr. Tapan presented data on 1,011 patients from 120 centers in 19 countries. The patients’ median age was 68 years (range, 28-95 years), and more than half were male (58%). Most patients (72%) were White, 20% were Hispanic/Latino, and 8% were Black/African American.

Most patients had NSCLC (82%), and most had stage IV disease (68%). Patients had received a median of one prior line of therapy.

As in earlier reports of TERAVOLT data, the mortality rate was 33%.

In a multivariate analysis, the following characteristics were associated with an increased risk of death:

• Male sex (odds ratio, 1.4).
• Older age (per 10 years; OR, 1.21).
• Performance score of 1 (OR, 1.73), 2 (OR, 4.74), and 3/4 (OR, 10.7).
• Four or more metastatic sites (OR, 3.05).

The following characteristics were associated with an increased risk of hospitalization in a multivariate analysis:

• Male sex (OR, 1.67).
• Older age (per 10 years; OR, 1.24).
• Performance score of 2 (OR, 4.47) and 3/4 (OR, 9.63).
• Four or more metastatic sites (OR, 4.0).
• Thymic carcinoma (OR, 3.58).
• Receiving radiation (OR, 2.1).

Race and ethnicity did not seem to affect the risk of death or hospitalization, “but we plan to conduct further analysis,” Dr. Tapan said.

Roxana Reyes, MD, of Hospital Clínic de Barcelona, said her hospital sees patients with lung cancer at high risk for COVID-19, but there is no screening program in place.

“We use medical consultations to focus on early diagnosis. We treat COVID-19 complications but lose a lot of patients. There is an opportunity to be found to find these patients sooner,” Dr. Reyes said.

She noted that COVID-19 will likely last a long time, and therefore “we have to protect against it and continue to diagnose lung cancer at earlier stages.”

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. Dr. Tapan has no relevant disclosures. The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer.

In the first ever placebo-controlled phase 3 trial in patients with relapsed mesothelioma, immunotherapy with nivolumab significantly improved both overall survival (OS) and progression-free survival (PFS).

The CONFIRM trial involved 330 previously treated patients with mesothelioma who were randomly assigned to nivolumab or placebo for 1 year or until progression or unacceptable toxicity.

Although recruitment to the study was stopped early because of the COVID-19 pandemic, enough data accrued to show that nivolumab improved overall survival by 28% over placebo, and increased PFS by 39%.

“Nivolumab was deemed a safe and effective treatment and should be considered a new treatment option for patients with relapsed mesothelioma,” said principal investigator Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester (England).

He presented the results at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Rina Hui, MD, PhD, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, who was not involved in the study, said that these results had been a “long time coming.”

CONFIRM has added “important, encouraging data on immunotherapy in the salvage setting,” Dr. Hui said, noting that two-thirds of patients had received two or more prior lines of therapy.

Dr. Fennel noted that “a significant clinical benefit was observed in the epithelioid subtype” of the disease but not in patients with nonepithelioid disease.

However, there was “no evidence” to support programmed death–ligand 1 (PD-L1) expression as predictive of outcomes, he added, which does appear to be the case in some trials on lung cancer and other tumors.

Commenting on these observations, Dr. Hui said that PD-L1 as a predictive biomarker in mesothelioma has been “controversial,” and she emphasized that the results from CONFIRM indicate “no evidence of PD-L1 being predictive.”

However, Dr. Hui questioned the other observation that clinical benefit appeared to be seen only in the epithelioid subtype.

She emphasized that nonepithelioid disease is known to be a “more aggressive, chemoresistant subtype ... with a steep decline in the survival curves.

“Therefore, a lot of patients would not have made it to a subsequent-line clinical trial, explaining why there were only 12% in the CONFIRM study,” and so the sample size may be “too small to detect a difference in outcome,” Dr. Hui said.

Consequently, Dr. Hui said she “would not deny patients with nonepithelioid histology from considering nivolumab in the salvage setting.”

She argued that there was “no clear predictive biomarker for patient selection” emerging from the CONFIRM data.

She agreed that, in patients with mesothelioma who have progressed following platinum/pemetrexed-based chemotherapy as in the first line, “monotherapy nivolumab now can be considered as a treatment option in the second- ... or third-line setting, after second-line chemotherapy”.

However, outstanding questions remain, including whether nivolumab “provides better outcomes than second-line single agent chemotherapy or second-line gemcitabine with the [vascular endothelial growth factor receptor] inhibitor ramucirumab.”

It may also be that nivolumab plus ipilimumab might be superior to nivolumab alone in the salvage setting.

But a more fundamental question is what should be considered for salvage therapy if nivolumab and ipilimumab have already been used in the first-line setting, Dr. Hui said.

Results of first-line immunotherapy combination trials are “eagerly awaited ... to determine and develop other salvage treatments,” she commented.

Responding on Twitter, Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust in Royal Tunbridge Wells, England, echoed these comments, saying that the results were “very exciting,” but he also “can’t wait to see the first-line chemo–immunotherapy data.”

Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, commented on Twitter that there was “not a lot of safety data” in the presentation and awaits their eventual publication.

He added that it is “good to have a positive trial” in relapsed mesothelioma, “though the first-line studies will decrease the eventual impact as immunotherapy becomes involved earlier in treatment.”

 

Details of the CONFIRM results 

Relapsed mesothelioma is an “unmet need,” and, until now, “there have been no phase 3 trials which have demonstrated improved overall survival,” Dr. Fennell said in his presentation.

However, three phase 2 trials have shown that immune checkpoint targeting via PD-1 has shown useful clinical activity as a monotherapy in the relapsed setting, and one of these trials has led to approval of nivolumab in Japan for this indication.

CONFIRM was an investigator-initiated phase 3 trial in patients with relapsed mesothelioma who had received more than one prior line of therapy and had a good performance status.

Recruitment began in April 2017, and the “target sample size was 336 patients,” Dr. Fennell said, but the trial was “halted at 332 patients (in March 2020) due to the peaking of the COVID-19 pandemic in the U.K.”

“However, at the time, it was felt there were sufficient events” to justify the current analysis of the coprimary endpoints of PFS and OS, despite the latter being 59 events short of the target of 291.

Dr. Fennell said that baseline characteristics were “generally well balanced” between the nivolumab (n = 221) and placebo (n = 111) arms.

However, there were more patients with a PD-L1 tumor proportion score (TPS) of at least 1% among the patients given nivolumab, at 37% versus 29% in the placebo arm.

After a median follow-up of 17.1 months in the nivolumab arm and 14.2 months in the placebo group, overall survival was significantly longer with the active treatment, at 9.2 months versus 6.6 months with placebo (hazard ratio, 0.72; P = .018).

The proportion of patients alive at 12 months was 39.5% in the nivolumab group and 26.9% in patients given placebo. Investigator-assessed PFS was also significantly longer with nivolumab, at 3.0 months versus 1.8 months with placebo (HR, 0.61; P < .001).

The proportion of patients disease free at 12 months was 14.5% with active treatment versus 4.9% months with the placebo.

“The role for PD-L1 as a potential biomarker was assessed,” Dr. Fennell said, using the Dako 22C3 antibody, with 150 nivolumab and 84 placebo patients divided into those with a TPS <1% or ≥1%.

He noted that PD-L1 expression in the tumor “did not predict survival for patients in the CONFIRM trial,” with neither PD-L1 positive nor PD-L1 negative patients demonstrating a significant improvement in overall survival with nivolumab vs placebo.

“For histology, epithelioid mesothelioma patients benefited from nivolumab,” Dr. Fennell continued, with a hazard ratio for death of 0.71 versus placebo (P = .021). “However, for the nonepithelioid subgroup, in this immature survival analysis ... the P value was not significant,” but this was a small subgroup of patients (12% in both nivolumab and placebo groups).

The safety analysis revealed that the proportion of patients with any serious adverse events, of any grade or grade 3 or higher, was almost identical between the active and placebo arms, Dr. Fennel reported. There were five deaths (3.6%) related to a serious adverse event in the nivolumab arm and four (5.3%) in the placebo group.

This research was funded by the Stand Up to Cancer campaign for Cancer Research UK, supported by Cancer Research UK core funding at the Southampton Clinical Trials Unit, and investigator-initiated support from Bristol-Myers Squibb for free drug labeling and distribution and funding for RECIST reporting. Dr. Fennell reported relationships with Astex Therapeutics, AstraZeneca, Atara Biotherapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Inventiva, Lab 21, Merck, and Roche. Dr. Hui reported relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Seagen.

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

In the first ever placebo-controlled phase 3 trial in patients with relapsed mesothelioma, immunotherapy with nivolumab significantly improved both overall survival (OS) and progression-free survival (PFS).

The CONFIRM trial involved 330 previously treated patients with mesothelioma who were randomly assigned to nivolumab or placebo for 1 year or until progression or unacceptable toxicity.

Although recruitment to the study was stopped early because of the COVID-19 pandemic, enough data accrued to show that nivolumab improved overall survival by 28% over placebo, and increased PFS by 39%.

“Nivolumab was deemed a safe and effective treatment and should be considered a new treatment option for patients with relapsed mesothelioma,” said principal investigator Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester (England).

He presented the results at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Rina Hui, MD, PhD, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, who was not involved in the study, said that these results had been a “long time coming.”

CONFIRM has added “important, encouraging data on immunotherapy in the salvage setting,” Dr. Hui said, noting that two-thirds of patients had received two or more prior lines of therapy.

Dr. Fennel noted that “a significant clinical benefit was observed in the epithelioid subtype” of the disease but not in patients with nonepithelioid disease.

However, there was “no evidence” to support programmed death–ligand 1 (PD-L1) expression as predictive of outcomes, he added, which does appear to be the case in some trials on lung cancer and other tumors.

Commenting on these observations, Dr. Hui said that PD-L1 as a predictive biomarker in mesothelioma has been “controversial,” and she emphasized that the results from CONFIRM indicate “no evidence of PD-L1 being predictive.”

However, Dr. Hui questioned the other observation that clinical benefit appeared to be seen only in the epithelioid subtype.

She emphasized that nonepithelioid disease is known to be a “more aggressive, chemoresistant subtype ... with a steep decline in the survival curves.

“Therefore, a lot of patients would not have made it to a subsequent-line clinical trial, explaining why there were only 12% in the CONFIRM study,” and so the sample size may be “too small to detect a difference in outcome,” Dr. Hui said.

Consequently, Dr. Hui said she “would not deny patients with nonepithelioid histology from considering nivolumab in the salvage setting.”

She argued that there was “no clear predictive biomarker for patient selection” emerging from the CONFIRM data.

She agreed that, in patients with mesothelioma who have progressed following platinum/pemetrexed-based chemotherapy as in the first line, “monotherapy nivolumab now can be considered as a treatment option in the second- ... or third-line setting, after second-line chemotherapy”.

However, outstanding questions remain, including whether nivolumab “provides better outcomes than second-line single agent chemotherapy or second-line gemcitabine with the [vascular endothelial growth factor receptor] inhibitor ramucirumab.”

It may also be that nivolumab plus ipilimumab might be superior to nivolumab alone in the salvage setting.

But a more fundamental question is what should be considered for salvage therapy if nivolumab and ipilimumab have already been used in the first-line setting, Dr. Hui said.

Results of first-line immunotherapy combination trials are “eagerly awaited ... to determine and develop other salvage treatments,” she commented.

Responding on Twitter, Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust in Royal Tunbridge Wells, England, echoed these comments, saying that the results were “very exciting,” but he also “can’t wait to see the first-line chemo–immunotherapy data.”

Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, commented on Twitter that there was “not a lot of safety data” in the presentation and awaits their eventual publication.

He added that it is “good to have a positive trial” in relapsed mesothelioma, “though the first-line studies will decrease the eventual impact as immunotherapy becomes involved earlier in treatment.”

 

Details of the CONFIRM results 

Relapsed mesothelioma is an “unmet need,” and, until now, “there have been no phase 3 trials which have demonstrated improved overall survival,” Dr. Fennell said in his presentation.

However, three phase 2 trials have shown that immune checkpoint targeting via PD-1 has shown useful clinical activity as a monotherapy in the relapsed setting, and one of these trials has led to approval of nivolumab in Japan for this indication.

CONFIRM was an investigator-initiated phase 3 trial in patients with relapsed mesothelioma who had received more than one prior line of therapy and had a good performance status.

Recruitment began in April 2017, and the “target sample size was 336 patients,” Dr. Fennell said, but the trial was “halted at 332 patients (in March 2020) due to the peaking of the COVID-19 pandemic in the U.K.”

“However, at the time, it was felt there were sufficient events” to justify the current analysis of the coprimary endpoints of PFS and OS, despite the latter being 59 events short of the target of 291.

Dr. Fennell said that baseline characteristics were “generally well balanced” between the nivolumab (n = 221) and placebo (n = 111) arms.

However, there were more patients with a PD-L1 tumor proportion score (TPS) of at least 1% among the patients given nivolumab, at 37% versus 29% in the placebo arm.

After a median follow-up of 17.1 months in the nivolumab arm and 14.2 months in the placebo group, overall survival was significantly longer with the active treatment, at 9.2 months versus 6.6 months with placebo (hazard ratio, 0.72; P = .018).

The proportion of patients alive at 12 months was 39.5% in the nivolumab group and 26.9% in patients given placebo. Investigator-assessed PFS was also significantly longer with nivolumab, at 3.0 months versus 1.8 months with placebo (HR, 0.61; P < .001).

The proportion of patients disease free at 12 months was 14.5% with active treatment versus 4.9% months with the placebo.

“The role for PD-L1 as a potential biomarker was assessed,” Dr. Fennell said, using the Dako 22C3 antibody, with 150 nivolumab and 84 placebo patients divided into those with a TPS <1% or ≥1%.

He noted that PD-L1 expression in the tumor “did not predict survival for patients in the CONFIRM trial,” with neither PD-L1 positive nor PD-L1 negative patients demonstrating a significant improvement in overall survival with nivolumab vs placebo.

“For histology, epithelioid mesothelioma patients benefited from nivolumab,” Dr. Fennell continued, with a hazard ratio for death of 0.71 versus placebo (P = .021). “However, for the nonepithelioid subgroup, in this immature survival analysis ... the P value was not significant,” but this was a small subgroup of patients (12% in both nivolumab and placebo groups).

The safety analysis revealed that the proportion of patients with any serious adverse events, of any grade or grade 3 or higher, was almost identical between the active and placebo arms, Dr. Fennel reported. There were five deaths (3.6%) related to a serious adverse event in the nivolumab arm and four (5.3%) in the placebo group.

This research was funded by the Stand Up to Cancer campaign for Cancer Research UK, supported by Cancer Research UK core funding at the Southampton Clinical Trials Unit, and investigator-initiated support from Bristol-Myers Squibb for free drug labeling and distribution and funding for RECIST reporting. Dr. Fennell reported relationships with Astex Therapeutics, AstraZeneca, Atara Biotherapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Inventiva, Lab 21, Merck, and Roche. Dr. Hui reported relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Seagen.

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

In the first ever placebo-controlled phase 3 trial in patients with relapsed mesothelioma, immunotherapy with nivolumab significantly improved both overall survival (OS) and progression-free survival (PFS).

The CONFIRM trial involved 330 previously treated patients with mesothelioma who were randomly assigned to nivolumab or placebo for 1 year or until progression or unacceptable toxicity.

Although recruitment to the study was stopped early because of the COVID-19 pandemic, enough data accrued to show that nivolumab improved overall survival by 28% over placebo, and increased PFS by 39%.

“Nivolumab was deemed a safe and effective treatment and should be considered a new treatment option for patients with relapsed mesothelioma,” said principal investigator Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester (England).

He presented the results at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Rina Hui, MD, PhD, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, who was not involved in the study, said that these results had been a “long time coming.”

CONFIRM has added “important, encouraging data on immunotherapy in the salvage setting,” Dr. Hui said, noting that two-thirds of patients had received two or more prior lines of therapy.

Dr. Fennel noted that “a significant clinical benefit was observed in the epithelioid subtype” of the disease but not in patients with nonepithelioid disease.

However, there was “no evidence” to support programmed death–ligand 1 (PD-L1) expression as predictive of outcomes, he added, which does appear to be the case in some trials on lung cancer and other tumors.

Commenting on these observations, Dr. Hui said that PD-L1 as a predictive biomarker in mesothelioma has been “controversial,” and she emphasized that the results from CONFIRM indicate “no evidence of PD-L1 being predictive.”

However, Dr. Hui questioned the other observation that clinical benefit appeared to be seen only in the epithelioid subtype.

She emphasized that nonepithelioid disease is known to be a “more aggressive, chemoresistant subtype ... with a steep decline in the survival curves.

“Therefore, a lot of patients would not have made it to a subsequent-line clinical trial, explaining why there were only 12% in the CONFIRM study,” and so the sample size may be “too small to detect a difference in outcome,” Dr. Hui said.

Consequently, Dr. Hui said she “would not deny patients with nonepithelioid histology from considering nivolumab in the salvage setting.”

She argued that there was “no clear predictive biomarker for patient selection” emerging from the CONFIRM data.

She agreed that, in patients with mesothelioma who have progressed following platinum/pemetrexed-based chemotherapy as in the first line, “monotherapy nivolumab now can be considered as a treatment option in the second- ... or third-line setting, after second-line chemotherapy”.

However, outstanding questions remain, including whether nivolumab “provides better outcomes than second-line single agent chemotherapy or second-line gemcitabine with the [vascular endothelial growth factor receptor] inhibitor ramucirumab.”

It may also be that nivolumab plus ipilimumab might be superior to nivolumab alone in the salvage setting.

But a more fundamental question is what should be considered for salvage therapy if nivolumab and ipilimumab have already been used in the first-line setting, Dr. Hui said.

Results of first-line immunotherapy combination trials are “eagerly awaited ... to determine and develop other salvage treatments,” she commented.

Responding on Twitter, Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust in Royal Tunbridge Wells, England, echoed these comments, saying that the results were “very exciting,” but he also “can’t wait to see the first-line chemo–immunotherapy data.”

Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, commented on Twitter that there was “not a lot of safety data” in the presentation and awaits their eventual publication.

He added that it is “good to have a positive trial” in relapsed mesothelioma, “though the first-line studies will decrease the eventual impact as immunotherapy becomes involved earlier in treatment.”

 

Details of the CONFIRM results 

Relapsed mesothelioma is an “unmet need,” and, until now, “there have been no phase 3 trials which have demonstrated improved overall survival,” Dr. Fennell said in his presentation.

However, three phase 2 trials have shown that immune checkpoint targeting via PD-1 has shown useful clinical activity as a monotherapy in the relapsed setting, and one of these trials has led to approval of nivolumab in Japan for this indication.

CONFIRM was an investigator-initiated phase 3 trial in patients with relapsed mesothelioma who had received more than one prior line of therapy and had a good performance status.

Recruitment began in April 2017, and the “target sample size was 336 patients,” Dr. Fennell said, but the trial was “halted at 332 patients (in March 2020) due to the peaking of the COVID-19 pandemic in the U.K.”

“However, at the time, it was felt there were sufficient events” to justify the current analysis of the coprimary endpoints of PFS and OS, despite the latter being 59 events short of the target of 291.

Dr. Fennell said that baseline characteristics were “generally well balanced” between the nivolumab (n = 221) and placebo (n = 111) arms.

However, there were more patients with a PD-L1 tumor proportion score (TPS) of at least 1% among the patients given nivolumab, at 37% versus 29% in the placebo arm.

After a median follow-up of 17.1 months in the nivolumab arm and 14.2 months in the placebo group, overall survival was significantly longer with the active treatment, at 9.2 months versus 6.6 months with placebo (hazard ratio, 0.72; P = .018).

The proportion of patients alive at 12 months was 39.5% in the nivolumab group and 26.9% in patients given placebo. Investigator-assessed PFS was also significantly longer with nivolumab, at 3.0 months versus 1.8 months with placebo (HR, 0.61; P < .001).

The proportion of patients disease free at 12 months was 14.5% with active treatment versus 4.9% months with the placebo.

“The role for PD-L1 as a potential biomarker was assessed,” Dr. Fennell said, using the Dako 22C3 antibody, with 150 nivolumab and 84 placebo patients divided into those with a TPS <1% or ≥1%.

He noted that PD-L1 expression in the tumor “did not predict survival for patients in the CONFIRM trial,” with neither PD-L1 positive nor PD-L1 negative patients demonstrating a significant improvement in overall survival with nivolumab vs placebo.

“For histology, epithelioid mesothelioma patients benefited from nivolumab,” Dr. Fennell continued, with a hazard ratio for death of 0.71 versus placebo (P = .021). “However, for the nonepithelioid subgroup, in this immature survival analysis ... the P value was not significant,” but this was a small subgroup of patients (12% in both nivolumab and placebo groups).

The safety analysis revealed that the proportion of patients with any serious adverse events, of any grade or grade 3 or higher, was almost identical between the active and placebo arms, Dr. Fennel reported. There were five deaths (3.6%) related to a serious adverse event in the nivolumab arm and four (5.3%) in the placebo group.

This research was funded by the Stand Up to Cancer campaign for Cancer Research UK, supported by Cancer Research UK core funding at the Southampton Clinical Trials Unit, and investigator-initiated support from Bristol-Myers Squibb for free drug labeling and distribution and funding for RECIST reporting. Dr. Fennell reported relationships with Astex Therapeutics, AstraZeneca, Atara Biotherapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Inventiva, Lab 21, Merck, and Roche. Dr. Hui reported relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Seagen.

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

Screening for lung cancer with low-dose computed tomography (LDCT) has thus far been targeted at individuals who smoke or have smoked, but the incidence of lung cancer has been found to be increasing among people who have never smoked, and they too should undergo screening, suggest researchers from Taiwan.

“Lung cancer in never-smokers is a global rising threat,” said lead researcher Pan-Chyr Yang, MD, PhD, chair professor at the National Taiwan University Hospital and academician of Academia Sinica, Taiwan.

In Taiwan, more than half of the cases of lung cancer occur in never-smokers; among female lung cancer patients, 93% are never-smokers.

The incidence of lung cancer – in particular, adenocarcinoma – is increasing in Taiwan, even though the prevalence of smoking has fallen dramatically in men in recent years and has remained low in women.

At the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, Dr. Yang presented new results that suggest “LDCT screening for never-smokers with high risk may be feasible.”

The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) recruited over 12,000 individuals aged 55-70 years who had never smoked or had done so more than 15 years previously and had risk factors such as a family history of the disease or passive smoke exposure, or who had regularly been exposed to frying food.

Participants underwent LDCT after chest x-ray, followed by biopsy if necessary.

These procedures detected largely invasive lung cancer in 2.6% of participants. Tumors were of stage 0-I in 95% of cases.

The lung cancer detection rate of 2.6% in TALENT in never-smokers is higher than has been found in large studies of smokers, including the 1.1% rate recorded in the NLST study and the 0.9% seen in the NELSON study.

The key factor associated with increased prevalence of lung cancer was a first-degree family history of the disease, Dr. Yang reported.

Notably, having a sister with lung cancer increased the risk for the disease by 78%. Having an affected brother doubled the risk. An increase in the number of first-degree relatives with lung cancer also significantly increased the risk.
 

More research needed

The TALENT study “provides new, very original evidence on lung cancer risks, and therefore lung cancer screening eligibility could be redefined in Asia, or at least in East Asia,” said the discussant for the paper, Ugo Pastorino, MD, director of thoracic surgery at IRCCS Istituto Nazionale dei Tumori Foundation, Milan.

However, he said that “more research is needed on lung cancer biology in nonsmokers.”

There is currently no follow-up or mortality data, and given the proportion of patients who underwent invasive procedures, it could be that more than 40% of those procedures were carried out in individuals with benign disease, he cautioned.

On Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said that although family history “emerges” from the study as a potential risk factor for lung cancer, “this analysis would be much more insightful with genomic analyses of these cancers.”

Devika Das, MD, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham, said that the study is “interesting,” given the rise of adenocarcinoma among never-smokers.

She agreed that further details and long-term outcomes are needed and said the key learning point was the need for a “robust” study of the biology of lung cancer in this population.

Lillian Leigh, an Australian lawyer and a lung cancer patient advocate, said the study “provides new evidence” on lung cancer risks.

“As an Asian never-smoker living with lung cancer, the TALENT trial results give me hope,” she said.
 

Details of TALENT findings

The TALENT study recruited individuals aged 55-70 years at 17 medical centers between February 2015 and July 2019.

Participants were required to be never-smokers or to have a smoking history of less than 10 pack-years and to have quit the habit more than 15 years previously.

They also had to have one of the following risk factors:

• Family history of lung cancer in up to third-degree relatives, in which case younger patients could be recruited.
• Environmental (passive) tobacco smoking history.
• Chronic lung disease, namely,  or .
• A cooking index ≥110, defined as 2/7 × the number of days of frying per week × the number of years cooking.
• Cooking without ventilation.

The participants underwent chest x-ray. If the x-ray proved negative, the team performed standard LDCT, examined blood and urine samples for lung cancer biomarkers, and administered standard questionnaires.

Participants who were found on LDCT to have solid or part-solid nodules greater than 6 mm in diameter or pure ground-glass nodules greater than 5 mm in diameter underwent biopsy or standard follow-up.

Individuals whose initial chest x-ray was positive underwent standard contrast-enhanced chest CT prior to biopsy or standard follow-up.

Of 13,207 individuals initially screened, 12,011 were enrolled. Of those, 73.8% were women. The mean age was 61.2 years, and 93.3% were never-smokers.

Among the participants, 46.4% had a first-degree family history of lung cancer; 3.0% had a second-degree family history; and 0.5% had a third-degree family history.

Environmental tobacco exposure was recorded in 83.2% of patients. Chronic lung disease was present in 9.8%; 36.7% had a cooking index ≥110; and 1.8 cooked without ventilation.

Dr. Yang said LDCT results were positive for 17.4% of patients, and 3.4% underwent invasive procedures.

Overall, lung cancer was detected in 313 participants (2.6%). Invasive lung cancer was detected in 255 (2.1%). Of those, 17.9% had multiple primary lung cancers.

Strikingly, 96.5% of the confirmed lung cancer cases were stage 0-I. The majority were stage IA, “which is higher than in other studies that have focused on heavy smokers,” Dr. Yang said. More than half of cases (58.5%) were invasive adenocarcinomas.

The prevalence of lung cancer was significantly higher among people who had a family history of the disease, at 3.2%, vs. 2.0% in those without, at a relative risk of 1.61 (P < .001).

The prevalence was higher still in individuals who had a first-degree family history of lung cancer, at 3.3%, giving a relative risk of 1.69 in comparison with those who did not have a family history (P < .001). The findings were nonsignificant for second- and third-degree relatives.

The relative risk increased even further when the first-degree relative who had a history of lung cancer was a sister, at 1.78 (P < .001), or a brother, at 2.00 (P < .001).

The relative risk was slightly lower if the patient’s relative was the mother, at 1.43 (P = .010), and was nonsignificant if the relative was the father (P = .077).

The risk for lung cancer also increased with an increase in the number of first-degree relatives with the disease, rising from 3.1% with one relative to 4.0% with two relatives, 6.7% with three relatives, and 9.1% with at least four relatives (P < .001). A similar pattern was seen for invasive lung cancer.

The other risk factors included in the study, such as environmental tobacco exposure, chronic lung disease, and cooking index, were not significantly associated with the prevalence of lung cancer.

No funding for the study has been disclosed. Dr. Yang has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Eli Lilly, Roche, GlaxoSmithKline, and ONO Pharma and has served on the advisory board of OBI Pharma, CHO Pharma, and Lin BioScience. Dr. Pastorino has disclosed no relevant financial relationships.

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

Screening for lung cancer with low-dose computed tomography (LDCT) has thus far been targeted at individuals who smoke or have smoked, but the incidence of lung cancer has been found to be increasing among people who have never smoked, and they too should undergo screening, suggest researchers from Taiwan.

“Lung cancer in never-smokers is a global rising threat,” said lead researcher Pan-Chyr Yang, MD, PhD, chair professor at the National Taiwan University Hospital and academician of Academia Sinica, Taiwan.

In Taiwan, more than half of the cases of lung cancer occur in never-smokers; among female lung cancer patients, 93% are never-smokers.

The incidence of lung cancer – in particular, adenocarcinoma – is increasing in Taiwan, even though the prevalence of smoking has fallen dramatically in men in recent years and has remained low in women.

At the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, Dr. Yang presented new results that suggest “LDCT screening for never-smokers with high risk may be feasible.”

The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) recruited over 12,000 individuals aged 55-70 years who had never smoked or had done so more than 15 years previously and had risk factors such as a family history of the disease or passive smoke exposure, or who had regularly been exposed to frying food.

Participants underwent LDCT after chest x-ray, followed by biopsy if necessary.

These procedures detected largely invasive lung cancer in 2.6% of participants. Tumors were of stage 0-I in 95% of cases.

The lung cancer detection rate of 2.6% in TALENT in never-smokers is higher than has been found in large studies of smokers, including the 1.1% rate recorded in the NLST study and the 0.9% seen in the NELSON study.

The key factor associated with increased prevalence of lung cancer was a first-degree family history of the disease, Dr. Yang reported.

Notably, having a sister with lung cancer increased the risk for the disease by 78%. Having an affected brother doubled the risk. An increase in the number of first-degree relatives with lung cancer also significantly increased the risk.
 

More research needed

The TALENT study “provides new, very original evidence on lung cancer risks, and therefore lung cancer screening eligibility could be redefined in Asia, or at least in East Asia,” said the discussant for the paper, Ugo Pastorino, MD, director of thoracic surgery at IRCCS Istituto Nazionale dei Tumori Foundation, Milan.

However, he said that “more research is needed on lung cancer biology in nonsmokers.”

There is currently no follow-up or mortality data, and given the proportion of patients who underwent invasive procedures, it could be that more than 40% of those procedures were carried out in individuals with benign disease, he cautioned.

On Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said that although family history “emerges” from the study as a potential risk factor for lung cancer, “this analysis would be much more insightful with genomic analyses of these cancers.”

Devika Das, MD, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham, said that the study is “interesting,” given the rise of adenocarcinoma among never-smokers.

She agreed that further details and long-term outcomes are needed and said the key learning point was the need for a “robust” study of the biology of lung cancer in this population.

Lillian Leigh, an Australian lawyer and a lung cancer patient advocate, said the study “provides new evidence” on lung cancer risks.

“As an Asian never-smoker living with lung cancer, the TALENT trial results give me hope,” she said.
 

Details of TALENT findings

The TALENT study recruited individuals aged 55-70 years at 17 medical centers between February 2015 and July 2019.

Participants were required to be never-smokers or to have a smoking history of less than 10 pack-years and to have quit the habit more than 15 years previously.

They also had to have one of the following risk factors:

• Family history of lung cancer in up to third-degree relatives, in which case younger patients could be recruited.
• Environmental (passive) tobacco smoking history.
• Chronic lung disease, namely,  or .
• A cooking index ≥110, defined as 2/7 × the number of days of frying per week × the number of years cooking.
• Cooking without ventilation.

The participants underwent chest x-ray. If the x-ray proved negative, the team performed standard LDCT, examined blood and urine samples for lung cancer biomarkers, and administered standard questionnaires.

Participants who were found on LDCT to have solid or part-solid nodules greater than 6 mm in diameter or pure ground-glass nodules greater than 5 mm in diameter underwent biopsy or standard follow-up.

Individuals whose initial chest x-ray was positive underwent standard contrast-enhanced chest CT prior to biopsy or standard follow-up.

Of 13,207 individuals initially screened, 12,011 were enrolled. Of those, 73.8% were women. The mean age was 61.2 years, and 93.3% were never-smokers.

Among the participants, 46.4% had a first-degree family history of lung cancer; 3.0% had a second-degree family history; and 0.5% had a third-degree family history.

Environmental tobacco exposure was recorded in 83.2% of patients. Chronic lung disease was present in 9.8%; 36.7% had a cooking index ≥110; and 1.8 cooked without ventilation.

Dr. Yang said LDCT results were positive for 17.4% of patients, and 3.4% underwent invasive procedures.

Overall, lung cancer was detected in 313 participants (2.6%). Invasive lung cancer was detected in 255 (2.1%). Of those, 17.9% had multiple primary lung cancers.

Strikingly, 96.5% of the confirmed lung cancer cases were stage 0-I. The majority were stage IA, “which is higher than in other studies that have focused on heavy smokers,” Dr. Yang said. More than half of cases (58.5%) were invasive adenocarcinomas.

The prevalence of lung cancer was significantly higher among people who had a family history of the disease, at 3.2%, vs. 2.0% in those without, at a relative risk of 1.61 (P < .001).

The prevalence was higher still in individuals who had a first-degree family history of lung cancer, at 3.3%, giving a relative risk of 1.69 in comparison with those who did not have a family history (P < .001). The findings were nonsignificant for second- and third-degree relatives.

The relative risk increased even further when the first-degree relative who had a history of lung cancer was a sister, at 1.78 (P < .001), or a brother, at 2.00 (P < .001).

The relative risk was slightly lower if the patient’s relative was the mother, at 1.43 (P = .010), and was nonsignificant if the relative was the father (P = .077).

The risk for lung cancer also increased with an increase in the number of first-degree relatives with the disease, rising from 3.1% with one relative to 4.0% with two relatives, 6.7% with three relatives, and 9.1% with at least four relatives (P < .001). A similar pattern was seen for invasive lung cancer.

The other risk factors included in the study, such as environmental tobacco exposure, chronic lung disease, and cooking index, were not significantly associated with the prevalence of lung cancer.

No funding for the study has been disclosed. Dr. Yang has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Eli Lilly, Roche, GlaxoSmithKline, and ONO Pharma and has served on the advisory board of OBI Pharma, CHO Pharma, and Lin BioScience. Dr. Pastorino has disclosed no relevant financial relationships.

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

Screening for lung cancer with low-dose computed tomography (LDCT) has thus far been targeted at individuals who smoke or have smoked, but the incidence of lung cancer has been found to be increasing among people who have never smoked, and they too should undergo screening, suggest researchers from Taiwan.

“Lung cancer in never-smokers is a global rising threat,” said lead researcher Pan-Chyr Yang, MD, PhD, chair professor at the National Taiwan University Hospital and academician of Academia Sinica, Taiwan.

In Taiwan, more than half of the cases of lung cancer occur in never-smokers; among female lung cancer patients, 93% are never-smokers.

The incidence of lung cancer – in particular, adenocarcinoma – is increasing in Taiwan, even though the prevalence of smoking has fallen dramatically in men in recent years and has remained low in women.

At the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, Dr. Yang presented new results that suggest “LDCT screening for never-smokers with high risk may be feasible.”

The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) recruited over 12,000 individuals aged 55-70 years who had never smoked or had done so more than 15 years previously and had risk factors such as a family history of the disease or passive smoke exposure, or who had regularly been exposed to frying food.

Participants underwent LDCT after chest x-ray, followed by biopsy if necessary.

These procedures detected largely invasive lung cancer in 2.6% of participants. Tumors were of stage 0-I in 95% of cases.

The lung cancer detection rate of 2.6% in TALENT in never-smokers is higher than has been found in large studies of smokers, including the 1.1% rate recorded in the NLST study and the 0.9% seen in the NELSON study.

The key factor associated with increased prevalence of lung cancer was a first-degree family history of the disease, Dr. Yang reported.

Notably, having a sister with lung cancer increased the risk for the disease by 78%. Having an affected brother doubled the risk. An increase in the number of first-degree relatives with lung cancer also significantly increased the risk.
 

More research needed

The TALENT study “provides new, very original evidence on lung cancer risks, and therefore lung cancer screening eligibility could be redefined in Asia, or at least in East Asia,” said the discussant for the paper, Ugo Pastorino, MD, director of thoracic surgery at IRCCS Istituto Nazionale dei Tumori Foundation, Milan.

However, he said that “more research is needed on lung cancer biology in nonsmokers.”

There is currently no follow-up or mortality data, and given the proportion of patients who underwent invasive procedures, it could be that more than 40% of those procedures were carried out in individuals with benign disease, he cautioned.

On Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said that although family history “emerges” from the study as a potential risk factor for lung cancer, “this analysis would be much more insightful with genomic analyses of these cancers.”

Devika Das, MD, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham, said that the study is “interesting,” given the rise of adenocarcinoma among never-smokers.

She agreed that further details and long-term outcomes are needed and said the key learning point was the need for a “robust” study of the biology of lung cancer in this population.

Lillian Leigh, an Australian lawyer and a lung cancer patient advocate, said the study “provides new evidence” on lung cancer risks.

“As an Asian never-smoker living with lung cancer, the TALENT trial results give me hope,” she said.
 

Details of TALENT findings

The TALENT study recruited individuals aged 55-70 years at 17 medical centers between February 2015 and July 2019.

Participants were required to be never-smokers or to have a smoking history of less than 10 pack-years and to have quit the habit more than 15 years previously.

They also had to have one of the following risk factors:

• Family history of lung cancer in up to third-degree relatives, in which case younger patients could be recruited.
• Environmental (passive) tobacco smoking history.
• Chronic lung disease, namely,  or .
• A cooking index ≥110, defined as 2/7 × the number of days of frying per week × the number of years cooking.
• Cooking without ventilation.

The participants underwent chest x-ray. If the x-ray proved negative, the team performed standard LDCT, examined blood and urine samples for lung cancer biomarkers, and administered standard questionnaires.

Participants who were found on LDCT to have solid or part-solid nodules greater than 6 mm in diameter or pure ground-glass nodules greater than 5 mm in diameter underwent biopsy or standard follow-up.

Individuals whose initial chest x-ray was positive underwent standard contrast-enhanced chest CT prior to biopsy or standard follow-up.

Of 13,207 individuals initially screened, 12,011 were enrolled. Of those, 73.8% were women. The mean age was 61.2 years, and 93.3% were never-smokers.

Among the participants, 46.4% had a first-degree family history of lung cancer; 3.0% had a second-degree family history; and 0.5% had a third-degree family history.

Environmental tobacco exposure was recorded in 83.2% of patients. Chronic lung disease was present in 9.8%; 36.7% had a cooking index ≥110; and 1.8 cooked without ventilation.

Dr. Yang said LDCT results were positive for 17.4% of patients, and 3.4% underwent invasive procedures.

Overall, lung cancer was detected in 313 participants (2.6%). Invasive lung cancer was detected in 255 (2.1%). Of those, 17.9% had multiple primary lung cancers.

Strikingly, 96.5% of the confirmed lung cancer cases were stage 0-I. The majority were stage IA, “which is higher than in other studies that have focused on heavy smokers,” Dr. Yang said. More than half of cases (58.5%) were invasive adenocarcinomas.

The prevalence of lung cancer was significantly higher among people who had a family history of the disease, at 3.2%, vs. 2.0% in those without, at a relative risk of 1.61 (P < .001).

The prevalence was higher still in individuals who had a first-degree family history of lung cancer, at 3.3%, giving a relative risk of 1.69 in comparison with those who did not have a family history (P < .001). The findings were nonsignificant for second- and third-degree relatives.

The relative risk increased even further when the first-degree relative who had a history of lung cancer was a sister, at 1.78 (P < .001), or a brother, at 2.00 (P < .001).

The relative risk was slightly lower if the patient’s relative was the mother, at 1.43 (P = .010), and was nonsignificant if the relative was the father (P = .077).

The risk for lung cancer also increased with an increase in the number of first-degree relatives with the disease, rising from 3.1% with one relative to 4.0% with two relatives, 6.7% with three relatives, and 9.1% with at least four relatives (P < .001). A similar pattern was seen for invasive lung cancer.

The other risk factors included in the study, such as environmental tobacco exposure, chronic lung disease, and cooking index, were not significantly associated with the prevalence of lung cancer.

No funding for the study has been disclosed. Dr. Yang has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Eli Lilly, Roche, GlaxoSmithKline, and ONO Pharma and has served on the advisory board of OBI Pharma, CHO Pharma, and Lin BioScience. Dr. Pastorino has disclosed no relevant financial relationships.

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

The Food and Drug Administration has granted accelerated approval for tepotinib (TEPMETKO) for the treatment of adults with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations.

Tepotinib is the first once-daily oral MET inhibitor approved for this patient population, and the approval applies to both treatment-naive and previously treated patients with NSCLC.

The approval was supported by results from the ongoing phase 2 VISION trial. Tepotinib produced an overall response rate of 43% in both treatment-naive patients (n = 69) and previously treated patients (n = 83) in this trial. The median duration of response was 10.8 months and 11.1 months, respectively.

Results of the primary analysis were published in The New England Journal of Medicine last year.

Study subjects received the recommended dose of 450 mg taken as two 225-mg tablets once daily with food until disease progression or unacceptable toxicity. Adverse reactions occurring in at least 20% of patients included edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity also have been reported with tepotinib.

Continued approval of tepotinib “may be contingent upon verification and description of clinical benefit in confirmatory trials,” the FDA stated in an approval announcement.

EMD Serono, the drug’s maker, also announced the approval in a press statement, calling tepotinib “an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations.”

“METex14 skipping occurs in approximately 3% to 4% of NSCLC cases, and patients with this aggressive lung cancer are often elderly and face a poor clinical prognosis,” Paul K. Paik, MD, the VISION primary investigator and clinical director of the thoracic oncology service at Memorial Sloan Kettering Cancer Center in New York, said in the statement.

“There is a pressing need for targeted treatments that have the potential to generate durable antitumor activity and improve the lives of patients with this challenging disease,” he added.

Andrea Ferris, president and chief executive officer of the nonprofit LUNGevity Foundation, further noted the “powerful progress” made in recent years with respect to understanding genetic mutations in NSCLC.

“The availability of a new precision medicine for NSCLC with METex14 skipping alterations advances patient access to targeted treatment and underscores the importance of routine comprehensive biomarker testing for patients with this challenging cancer,” she said in the statement.

Tepotinib was approved in Japan in March 2020. The drug previously received breakthrough therapy designation and orphan drug designation from the FDA. A marketing authorization application for tepotinib was validated by the European Medicines Agency in November 2020 for a similar indication, EMD Serono reported, adding that applications “have also been submitted in Australia, Switzerland, and Canada under the FDA’s Project Orbis initiative, which provides a framework for concurrent submission and review of oncology medicines among international partners.”

Other phase 2 studies of tepotinib are ongoing. The INSIGHT 2 study is designed to test tepotinib in combination with osimertinib in MET amplified, advanced, or metastatic NSCLC with activating EGFR mutations that has progressed following first-line treatment with osimertinib. The PERSPECTIVE study is designed to test tepotinib in combination with cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer with acquired resistance to anti-EGFR antibody targeting therapy due to MET amplification.

For more details on tepotinib, see the full prescribing information.

[email protected]

The Food and Drug Administration has granted accelerated approval for tepotinib (TEPMETKO) for the treatment of adults with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations.

Tepotinib is the first once-daily oral MET inhibitor approved for this patient population, and the approval applies to both treatment-naive and previously treated patients with NSCLC.

The approval was supported by results from the ongoing phase 2 VISION trial. Tepotinib produced an overall response rate of 43% in both treatment-naive patients (n = 69) and previously treated patients (n = 83) in this trial. The median duration of response was 10.8 months and 11.1 months, respectively.

Results of the primary analysis were published in The New England Journal of Medicine last year.

Study subjects received the recommended dose of 450 mg taken as two 225-mg tablets once daily with food until disease progression or unacceptable toxicity. Adverse reactions occurring in at least 20% of patients included edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity also have been reported with tepotinib.

Continued approval of tepotinib “may be contingent upon verification and description of clinical benefit in confirmatory trials,” the FDA stated in an approval announcement.

EMD Serono, the drug’s maker, also announced the approval in a press statement, calling tepotinib “an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations.”

“METex14 skipping occurs in approximately 3% to 4% of NSCLC cases, and patients with this aggressive lung cancer are often elderly and face a poor clinical prognosis,” Paul K. Paik, MD, the VISION primary investigator and clinical director of the thoracic oncology service at Memorial Sloan Kettering Cancer Center in New York, said in the statement.

“There is a pressing need for targeted treatments that have the potential to generate durable antitumor activity and improve the lives of patients with this challenging disease,” he added.

Andrea Ferris, president and chief executive officer of the nonprofit LUNGevity Foundation, further noted the “powerful progress” made in recent years with respect to understanding genetic mutations in NSCLC.

“The availability of a new precision medicine for NSCLC with METex14 skipping alterations advances patient access to targeted treatment and underscores the importance of routine comprehensive biomarker testing for patients with this challenging cancer,” she said in the statement.

Tepotinib was approved in Japan in March 2020. The drug previously received breakthrough therapy designation and orphan drug designation from the FDA. A marketing authorization application for tepotinib was validated by the European Medicines Agency in November 2020 for a similar indication, EMD Serono reported, adding that applications “have also been submitted in Australia, Switzerland, and Canada under the FDA’s Project Orbis initiative, which provides a framework for concurrent submission and review of oncology medicines among international partners.”

Other phase 2 studies of tepotinib are ongoing. The INSIGHT 2 study is designed to test tepotinib in combination with osimertinib in MET amplified, advanced, or metastatic NSCLC with activating EGFR mutations that has progressed following first-line treatment with osimertinib. The PERSPECTIVE study is designed to test tepotinib in combination with cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer with acquired resistance to anti-EGFR antibody targeting therapy due to MET amplification.

For more details on tepotinib, see the full prescribing information.

[email protected]

The Food and Drug Administration has granted accelerated approval for tepotinib (TEPMETKO) for the treatment of adults with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations.

Tepotinib is the first once-daily oral MET inhibitor approved for this patient population, and the approval applies to both treatment-naive and previously treated patients with NSCLC.

The approval was supported by results from the ongoing phase 2 VISION trial. Tepotinib produced an overall response rate of 43% in both treatment-naive patients (n = 69) and previously treated patients (n = 83) in this trial. The median duration of response was 10.8 months and 11.1 months, respectively.

Results of the primary analysis were published in The New England Journal of Medicine last year.

Study subjects received the recommended dose of 450 mg taken as two 225-mg tablets once daily with food until disease progression or unacceptable toxicity. Adverse reactions occurring in at least 20% of patients included edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity also have been reported with tepotinib.

Continued approval of tepotinib “may be contingent upon verification and description of clinical benefit in confirmatory trials,” the FDA stated in an approval announcement.

EMD Serono, the drug’s maker, also announced the approval in a press statement, calling tepotinib “an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations.”

“METex14 skipping occurs in approximately 3% to 4% of NSCLC cases, and patients with this aggressive lung cancer are often elderly and face a poor clinical prognosis,” Paul K. Paik, MD, the VISION primary investigator and clinical director of the thoracic oncology service at Memorial Sloan Kettering Cancer Center in New York, said in the statement.

“There is a pressing need for targeted treatments that have the potential to generate durable antitumor activity and improve the lives of patients with this challenging disease,” he added.

Andrea Ferris, president and chief executive officer of the nonprofit LUNGevity Foundation, further noted the “powerful progress” made in recent years with respect to understanding genetic mutations in NSCLC.

“The availability of a new precision medicine for NSCLC with METex14 skipping alterations advances patient access to targeted treatment and underscores the importance of routine comprehensive biomarker testing for patients with this challenging cancer,” she said in the statement.

Tepotinib was approved in Japan in March 2020. The drug previously received breakthrough therapy designation and orphan drug designation from the FDA. A marketing authorization application for tepotinib was validated by the European Medicines Agency in November 2020 for a similar indication, EMD Serono reported, adding that applications “have also been submitted in Australia, Switzerland, and Canada under the FDA’s Project Orbis initiative, which provides a framework for concurrent submission and review of oncology medicines among international partners.”

Other phase 2 studies of tepotinib are ongoing. The INSIGHT 2 study is designed to test tepotinib in combination with osimertinib in MET amplified, advanced, or metastatic NSCLC with activating EGFR mutations that has progressed following first-line treatment with osimertinib. The PERSPECTIVE study is designed to test tepotinib in combination with cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer with acquired resistance to anti-EGFR antibody targeting therapy due to MET amplification.

For more details on tepotinib, see the full prescribing information.

[email protected]

Lung cancer experts have been rejoicing over new longer-term results that continue to show the combination of immunotherapy and chemotherapy doubles survival, compared with chemotherapy alone.

The results are from a 4-year follow-up of 160 patients with previously untreated stage IV non–small cell lung cancer (NSCLC) taking part in the KEYNOTE-189 trial of immunotherapy with pembrolizumab plus pemetrexed–platinum chemotherapy versus chemotherapy plus placebo.

After a median follow-up of 46.3 months, the median overall survival (OS) in the intention-to-treat population was 22.0 months with the combination versus 10.6 months with chemotherapy alone (hazard ratio, 0.60).

A similar pattern was seen for progression-free survival (PFS), with patients receiving the combination having a longer median PFS, at 9.0 months versus 4.9 months with chemotherapy alone (HR, 0.50).

“Stellar data,” Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust, Royal Tunbridge Wells, England, exclaimed on Twitter.

He described the results for the programmed death-ligand 1 (PD-L1) expression subgroups as “astonishing” and singled out the performance of the combination therapy in patients with very low (<1%) tumor PD-L1 expression, showing more than 23% of patients were alive at 3 years versus just over 5% in the group given chemotherapy alone.

Charu Aggarwal, MD, MPH, Leslye M. Heisler associate professor for lung cancer excellence, Penn Medicine, Philadelphia, said the outcomes with the combination of chemotherapy and immunotherapy were “terrific.”

Sandip P. Patel, MD, medical oncologist, associate professor of medicine, University of California, San Diego, agreed that these long-term results were “very impressive.” However, he noted the “full effect” of chemotherapy plus immunotherapy has not “fully been captured in our overall cancer mortality statistics in the U.S. yet.”

The new results were presented at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Previous results from KEYNOTE-189 had already demonstrated that, after a median follow-up of 10.5 months, adding pembrolizumab to chemotherapy significantly improves both OS and PFS, compared with chemotherapy alone.

The latest results show that the combination “continued to provide overall survival and progression-free survival benefit” in extended follow-up, said study presenter Jhanelle Elaine Gray, MD, chair, department of thoracic oncology, Moffitt Cancer Center, Tampa.

The 3-year OS rate with pembrolizumab plus chemotherapy, compared with chemotherapy alone was 31.3% versus 17.4%, and the estimated 3-year PFS was 11.8% versus 1.3%.

Substantial improvements were even seen in patients with tumors that had a low level of PD-L1 expression (measured as the PD-L1 tumor proportion score [TPS]).

Dr. Gray highlighted the finding that the survival benefit with pembrolizumab plus chemotherapy was seen regardless of PD-L1 expression in the tumor, with a hazard ratio versus chemotherapy alone of 0.71 in patients with a TPS ≥ 50%, 0.66 in those with a TPS of 1%-49%, and 0.52 in patients with a TPS less than 1%. A similar pattern was seen with PFS, with a hazard ratio of 0.36 in patients with a TPS of at least 50%, 0.54 in those with a TPS of 1%-49%, and 0.68 in patients with a TPS less than 1%.

In addition, overall response rate and duration of response were also improved with combination therapy, regardless of tumor PD-L1 expression.

Among 56 patients who completed 35 cycles of pembrolizumab, the objective response rate was 87.5% (with 10.7% having a complete response and 76.8% a partial response).

At the data cutoff, 45 patients were alive, 28 did not have progressive disease, and seven had started a second course of pembrolizumab.

The side effect profile of the combination was “manageable,” Dr. Gray reported.

The combination arm was associated with more grade 3-5 treatment-related adverse events than the chemotherapy alone arm, at 52.1% versus 42.1%, and more grade 3-5 immune-related adverse events and infusion reactions, at 27.7% versus 13.4%.

Events leading to treatment discontinuation were also more common with pembrolizumab plus chemotherapy than chemotherapy, at 27.4% versus 9.9%.

The combination of pembrolizumab plus pemetrexed-platinum has already become “a standard-of-care therapy for patients with newly diagnosed metastatic nonsquamous NSCLC,” Dr. Gray commented.

The study was funded by Merck. Dr. Gray disclosed relationships with Array, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, and Merck.

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

Lung cancer experts have been rejoicing over new longer-term results that continue to show the combination of immunotherapy and chemotherapy doubles survival, compared with chemotherapy alone.

The results are from a 4-year follow-up of 160 patients with previously untreated stage IV non–small cell lung cancer (NSCLC) taking part in the KEYNOTE-189 trial of immunotherapy with pembrolizumab plus pemetrexed–platinum chemotherapy versus chemotherapy plus placebo.

After a median follow-up of 46.3 months, the median overall survival (OS) in the intention-to-treat population was 22.0 months with the combination versus 10.6 months with chemotherapy alone (hazard ratio, 0.60).

A similar pattern was seen for progression-free survival (PFS), with patients receiving the combination having a longer median PFS, at 9.0 months versus 4.9 months with chemotherapy alone (HR, 0.50).

“Stellar data,” Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust, Royal Tunbridge Wells, England, exclaimed on Twitter.

He described the results for the programmed death-ligand 1 (PD-L1) expression subgroups as “astonishing” and singled out the performance of the combination therapy in patients with very low (<1%) tumor PD-L1 expression, showing more than 23% of patients were alive at 3 years versus just over 5% in the group given chemotherapy alone.

Charu Aggarwal, MD, MPH, Leslye M. Heisler associate professor for lung cancer excellence, Penn Medicine, Philadelphia, said the outcomes with the combination of chemotherapy and immunotherapy were “terrific.”

Sandip P. Patel, MD, medical oncologist, associate professor of medicine, University of California, San Diego, agreed that these long-term results were “very impressive.” However, he noted the “full effect” of chemotherapy plus immunotherapy has not “fully been captured in our overall cancer mortality statistics in the U.S. yet.”

The new results were presented at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Previous results from KEYNOTE-189 had already demonstrated that, after a median follow-up of 10.5 months, adding pembrolizumab to chemotherapy significantly improves both OS and PFS, compared with chemotherapy alone.

The latest results show that the combination “continued to provide overall survival and progression-free survival benefit” in extended follow-up, said study presenter Jhanelle Elaine Gray, MD, chair, department of thoracic oncology, Moffitt Cancer Center, Tampa.

The 3-year OS rate with pembrolizumab plus chemotherapy, compared with chemotherapy alone was 31.3% versus 17.4%, and the estimated 3-year PFS was 11.8% versus 1.3%.

Substantial improvements were even seen in patients with tumors that had a low level of PD-L1 expression (measured as the PD-L1 tumor proportion score [TPS]).

Dr. Gray highlighted the finding that the survival benefit with pembrolizumab plus chemotherapy was seen regardless of PD-L1 expression in the tumor, with a hazard ratio versus chemotherapy alone of 0.71 in patients with a TPS ≥ 50%, 0.66 in those with a TPS of 1%-49%, and 0.52 in patients with a TPS less than 1%. A similar pattern was seen with PFS, with a hazard ratio of 0.36 in patients with a TPS of at least 50%, 0.54 in those with a TPS of 1%-49%, and 0.68 in patients with a TPS less than 1%.

In addition, overall response rate and duration of response were also improved with combination therapy, regardless of tumor PD-L1 expression.

Among 56 patients who completed 35 cycles of pembrolizumab, the objective response rate was 87.5% (with 10.7% having a complete response and 76.8% a partial response).

At the data cutoff, 45 patients were alive, 28 did not have progressive disease, and seven had started a second course of pembrolizumab.

The side effect profile of the combination was “manageable,” Dr. Gray reported.

The combination arm was associated with more grade 3-5 treatment-related adverse events than the chemotherapy alone arm, at 52.1% versus 42.1%, and more grade 3-5 immune-related adverse events and infusion reactions, at 27.7% versus 13.4%.

Events leading to treatment discontinuation were also more common with pembrolizumab plus chemotherapy than chemotherapy, at 27.4% versus 9.9%.

The combination of pembrolizumab plus pemetrexed-platinum has already become “a standard-of-care therapy for patients with newly diagnosed metastatic nonsquamous NSCLC,” Dr. Gray commented.

The study was funded by Merck. Dr. Gray disclosed relationships with Array, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, and Merck.

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

Lung cancer experts have been rejoicing over new longer-term results that continue to show the combination of immunotherapy and chemotherapy doubles survival, compared with chemotherapy alone.

The results are from a 4-year follow-up of 160 patients with previously untreated stage IV non–small cell lung cancer (NSCLC) taking part in the KEYNOTE-189 trial of immunotherapy with pembrolizumab plus pemetrexed–platinum chemotherapy versus chemotherapy plus placebo.

After a median follow-up of 46.3 months, the median overall survival (OS) in the intention-to-treat population was 22.0 months with the combination versus 10.6 months with chemotherapy alone (hazard ratio, 0.60).

A similar pattern was seen for progression-free survival (PFS), with patients receiving the combination having a longer median PFS, at 9.0 months versus 4.9 months with chemotherapy alone (HR, 0.50).

“Stellar data,” Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust, Royal Tunbridge Wells, England, exclaimed on Twitter.

He described the results for the programmed death-ligand 1 (PD-L1) expression subgroups as “astonishing” and singled out the performance of the combination therapy in patients with very low (<1%) tumor PD-L1 expression, showing more than 23% of patients were alive at 3 years versus just over 5% in the group given chemotherapy alone.

Charu Aggarwal, MD, MPH, Leslye M. Heisler associate professor for lung cancer excellence, Penn Medicine, Philadelphia, said the outcomes with the combination of chemotherapy and immunotherapy were “terrific.”

Sandip P. Patel, MD, medical oncologist, associate professor of medicine, University of California, San Diego, agreed that these long-term results were “very impressive.” However, he noted the “full effect” of chemotherapy plus immunotherapy has not “fully been captured in our overall cancer mortality statistics in the U.S. yet.”

The new results were presented at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Previous results from KEYNOTE-189 had already demonstrated that, after a median follow-up of 10.5 months, adding pembrolizumab to chemotherapy significantly improves both OS and PFS, compared with chemotherapy alone.

The latest results show that the combination “continued to provide overall survival and progression-free survival benefit” in extended follow-up, said study presenter Jhanelle Elaine Gray, MD, chair, department of thoracic oncology, Moffitt Cancer Center, Tampa.

The 3-year OS rate with pembrolizumab plus chemotherapy, compared with chemotherapy alone was 31.3% versus 17.4%, and the estimated 3-year PFS was 11.8% versus 1.3%.

Substantial improvements were even seen in patients with tumors that had a low level of PD-L1 expression (measured as the PD-L1 tumor proportion score [TPS]).

Dr. Gray highlighted the finding that the survival benefit with pembrolizumab plus chemotherapy was seen regardless of PD-L1 expression in the tumor, with a hazard ratio versus chemotherapy alone of 0.71 in patients with a TPS ≥ 50%, 0.66 in those with a TPS of 1%-49%, and 0.52 in patients with a TPS less than 1%. A similar pattern was seen with PFS, with a hazard ratio of 0.36 in patients with a TPS of at least 50%, 0.54 in those with a TPS of 1%-49%, and 0.68 in patients with a TPS less than 1%.

In addition, overall response rate and duration of response were also improved with combination therapy, regardless of tumor PD-L1 expression.

Among 56 patients who completed 35 cycles of pembrolizumab, the objective response rate was 87.5% (with 10.7% having a complete response and 76.8% a partial response).

At the data cutoff, 45 patients were alive, 28 did not have progressive disease, and seven had started a second course of pembrolizumab.

The side effect profile of the combination was “manageable,” Dr. Gray reported.

The combination arm was associated with more grade 3-5 treatment-related adverse events than the chemotherapy alone arm, at 52.1% versus 42.1%, and more grade 3-5 immune-related adverse events and infusion reactions, at 27.7% versus 13.4%.

Events leading to treatment discontinuation were also more common with pembrolizumab plus chemotherapy than chemotherapy, at 27.4% versus 9.9%.

The combination of pembrolizumab plus pemetrexed-platinum has already become “a standard-of-care therapy for patients with newly diagnosed metastatic nonsquamous NSCLC,” Dr. Gray commented.

The study was funded by Merck. Dr. Gray disclosed relationships with Array, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, and Merck.

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