Federal Practitioner

Key clinical point: GINS complex subunit 4 (GINS4) is a prognostic biomarker in hepatocellular carcinoma (HCC).

Major finding: GINS4 was overexpressed in HCC. Higher GINS4 expression correlated with higher TNM stage and histologic grade (P less than .0001). Kaplan-Meier survival curves linked higher GINS4 expression with worse overall survival (hazard ratio for death, 1.84; P = .004).

Study details: Findings are from a retrospective study of 1,084 patients with HCC, as well as patients with hepatic cirrhosis and healthy controls. GINS4 was analyzed by using existing publicly available databases and immunohistochemistry of specimens from 35 of the HCC patients.

Disclosures: The National Natural Science Foundation of China and the Hunan Province Science and Technology plan provided funding. The researchers reported having no conflicts of interest.

Source: Zhang Z et al. Front Oncol. 2021 Mar 25. doi: 10.3389/fonc.2021.654185

Key clinical point: GINS complex subunit 4 (GINS4) is a prognostic biomarker in hepatocellular carcinoma (HCC).

Major finding: GINS4 was overexpressed in HCC. Higher GINS4 expression correlated with higher TNM stage and histologic grade (P less than .0001). Kaplan-Meier survival curves linked higher GINS4 expression with worse overall survival (hazard ratio for death, 1.84; P = .004).

Study details: Findings are from a retrospective study of 1,084 patients with HCC, as well as patients with hepatic cirrhosis and healthy controls. GINS4 was analyzed by using existing publicly available databases and immunohistochemistry of specimens from 35 of the HCC patients.

Disclosures: The National Natural Science Foundation of China and the Hunan Province Science and Technology plan provided funding. The researchers reported having no conflicts of interest.

Source: Zhang Z et al. Front Oncol. 2021 Mar 25. doi: 10.3389/fonc.2021.654185

Key clinical point: GINS complex subunit 4 (GINS4) is a prognostic biomarker in hepatocellular carcinoma (HCC).

Major finding: GINS4 was overexpressed in HCC. Higher GINS4 expression correlated with higher TNM stage and histologic grade (P less than .0001). Kaplan-Meier survival curves linked higher GINS4 expression with worse overall survival (hazard ratio for death, 1.84; P = .004).

Study details: Findings are from a retrospective study of 1,084 patients with HCC, as well as patients with hepatic cirrhosis and healthy controls. GINS4 was analyzed by using existing publicly available databases and immunohistochemistry of specimens from 35 of the HCC patients.

Disclosures: The National Natural Science Foundation of China and the Hunan Province Science and Technology plan provided funding. The researchers reported having no conflicts of interest.

Source: Zhang Z et al. Front Oncol. 2021 Mar 25. doi: 10.3389/fonc.2021.654185

Key clinical point: Compared with lenvatinib alone, triple combination therapy with lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy appeared to demonstrate acceptable safety and improved survival in patients with advanced hepatocellular carcinoma (HCC).

Major finding: Median progression-free survival was 11.1 months with triple combination therapy vs 5.1 months with lenvatinib alone (hazard ratio, 0.48; P less than .001). Compared with lenvatinib alone, triple combination therapy was associated with a significantly higher rate of grade 3-4 neutropenia, thrombocytopenia, and nausea.

Study details: Findings come from a retrospective study of 157 patients with unresectable HCC, of whom 86 received lenvatinib and 71 received lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy with FOLFAX (oxaliplatin, leucovorin, and 5-fluorouracil).

Disclosures: The study was funded by the National Key R&D Program of China, National Natural Science Foundation of China, and National Science and Technology Major Project of China. The researchers reported having no conflicts of interest.

Source:  He M-K et al. Ther Adv Med Oncol. 2021 Mar 25. doi: 10.1177/17588359211002720

Key clinical point: Compared with lenvatinib alone, triple combination therapy with lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy appeared to demonstrate acceptable safety and improved survival in patients with advanced hepatocellular carcinoma (HCC).

Major finding: Median progression-free survival was 11.1 months with triple combination therapy vs 5.1 months with lenvatinib alone (hazard ratio, 0.48; P less than .001). Compared with lenvatinib alone, triple combination therapy was associated with a significantly higher rate of grade 3-4 neutropenia, thrombocytopenia, and nausea.

Study details: Findings come from a retrospective study of 157 patients with unresectable HCC, of whom 86 received lenvatinib and 71 received lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy with FOLFAX (oxaliplatin, leucovorin, and 5-fluorouracil).

Disclosures: The study was funded by the National Key R&D Program of China, National Natural Science Foundation of China, and National Science and Technology Major Project of China. The researchers reported having no conflicts of interest.

Source:  He M-K et al. Ther Adv Med Oncol. 2021 Mar 25. doi: 10.1177/17588359211002720

Key clinical point: Compared with lenvatinib alone, triple combination therapy with lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy appeared to demonstrate acceptable safety and improved survival in patients with advanced hepatocellular carcinoma (HCC).

Major finding: Median progression-free survival was 11.1 months with triple combination therapy vs 5.1 months with lenvatinib alone (hazard ratio, 0.48; P less than .001). Compared with lenvatinib alone, triple combination therapy was associated with a significantly higher rate of grade 3-4 neutropenia, thrombocytopenia, and nausea.

Study details: Findings come from a retrospective study of 157 patients with unresectable HCC, of whom 86 received lenvatinib and 71 received lenvatinib, toripalimab, and hepatic arterial infusion chemotherapy with FOLFAX (oxaliplatin, leucovorin, and 5-fluorouracil).

Disclosures: The study was funded by the National Key R&D Program of China, National Natural Science Foundation of China, and National Science and Technology Major Project of China. The researchers reported having no conflicts of interest.

Source:  He M-K et al. Ther Adv Med Oncol. 2021 Mar 25. doi: 10.1177/17588359211002720

Physicians’ trust in health care system leaders has taken a steep drop during the COVID-19 pandemic, according to a survey conducted by NORC at the University of Chicago on behalf of the American Board of Internal Medicine Foundation.

Survey results, released May 21, indicate that 30% of physicians say their trust in the U.S. health care system and health care leadership has decreased during the pandemic. Only 18% reported an increase in trust.

Physicians, however, have great trust in their fellow clinicians.

In the survey of 600 physicians, 94% said they trust doctors within their practice; 85% trusted doctors outside of their practice; and 89% trusted nurses. That trust increased during the pandemic, with 41% saying their trust in fellow physicians rose and 37% saying their trust in nurses did.

In a separate survey, NORC asked patients about their trust in various aspects of health care. Among 2,069 respondents, a wide majority reported that they trust doctors (84%) and nurses (85%), but only 64% trusted the health care system as a whole. One in three consumers (32%) said their trust in the health care system decreased during the pandemic, compared with 11% who said their trust increased.

The ABIM Foundation released the research findings on May 21 as part of Building Trust, a national campaign that aims to boost trust among patients, clinicians, system leaders, researchers, and others.

Richard J. Baron, MD, president and chief executive officer of the ABIM Foundation, said in an interview, “Clearly there’s lower trust in health care organization leaders and executives, and that’s troubling.

“Science by itself is not enough,” he said. “Becoming trustworthy has to be a core project of everybody in health care.”

Deterioration in physicians’ trust during the pandemic comes in part from failed promises of adequate personal protective equipment and some physicians’ loss of income as a result of the crisis, Dr. Baron said.

He added that the vaccine rollout was very uneven and that policies as to which elective procedures could be performed were handled differently in different parts of the country.

He also noted that, early on, transparency was lacking as to how many COVID patients hospitals were treating, which may have contributed to the decrease in trust in the system.
 

Fear of being known as ‘the COVID hospital’

Hospitals were afraid of being known as “the COVID hospital” and losing patients who were afraid to come there, Dr. Baron said.

He said the COVID-19 epidemic exacerbated problems regarding trust, but that trust has been declining for some time. The Building Trust campaign will focus on solutions in breaches of trust as physicians move increasingly toward being employees of huge systems, according to Dr. Baron.

However, trust works both ways, Dr. Baron notes. Physicians can be champions for their health care system or “throw the system under the bus,” he said.

For example, if a patient complains about the appointment system, clinicians who trust their institutions may say the system usually works and that they will try to make sure the patient has a better experience next time. Clinicians without trust may say they agree that the health care system doesn’t know what it is doing, and patients may further lose confidence when physicians validate their complaint, and patients may then go elsewhere.
 

78% of patients trust primary care doctor

When asked whether they trust their primary care physician, 78% of patients said yes. However, trust in doctors was higher among people who were older (90%), White (82%), or had high income (89%). Among people reporting lower trust, 25% said their physician spends too little time with them, and 14% said their doctor does not know or listen to them.

The survey shows that government agencies have work to do to earn trust. Responses indicate that 43% of physicians said they have “complete trust” in government health care agencies, such as the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention, which is substantially higher than other parts of the health care system. However, trust in agencies declined for 43% of physician respondents and increased for 21%.

Dhruv Khullar, MD, MPP, of the department of health policy and economics at Weill Cornell Medical College in New York, told this news organization the survey results match what he sees anecdotally in medicine – that physicians have been losing trust in the system but not in their colleagues.

He said the sample size of 600 is enough to be influential, though he said he would like to know the response rate, which was not calculated for this survey.

He added that, in large part, physicians’ lack of trust in their systems may come from generally being asked to see more patients and to meet more metrics during the same or shorter periods.

Physicians’ lack of trust in the system can have significant consequences, he said. It can lead to burnout, which has been linked with poorer quality of care and physician turnover, he noted.

COVID-19 led some physicians to wonder whether their system had their best interests at heart, insofar as access to adequate medicines and supplies as well as emotional support were inconsistent, Dr. Khullar said.

He said that to regain trust health care systems need to ask themselves questions in three areas. The first is whether their goals are focused on the best interest of the organization or the best interest of the patient.

“Next is competency,” Dr. Khullar said. “Maybe your motives are right, but are you able to deliver? Are you delivering a good product, whether clinical services or something else?”

The third area is transparency, he said. “Are you going to be honest and forthright in what we’re doing and where we’re going?”

Caroline Pearson, senior vice president of health care strategy for NORC, said the emailed survey was conducted between Dec. 29, 2020, and Feb. 5, 2021, with a health care survey partner that maintains a nationwide panel of physicians across specialties.

She said this report is fairly novel insofar as surveys are more typically conducted regarding patients’ trust of their doctors or of the health care system.

Ms. Pearson said because health care is delivered in teams, understanding the level of trust among the entities helps ensure that care will be delivered effectively and seamlessly with high quality.

“We want our patients to trust our doctors, but we really want doctors to trust each other and trust the hospitals and systems in which they’re working,” she said.

Dr. Baron, Ms. Pearson, and Dr. Khullar report no relevant financial relationships.

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

Physicians’ trust in health care system leaders has taken a steep drop during the COVID-19 pandemic, according to a survey conducted by NORC at the University of Chicago on behalf of the American Board of Internal Medicine Foundation.

Survey results, released May 21, indicate that 30% of physicians say their trust in the U.S. health care system and health care leadership has decreased during the pandemic. Only 18% reported an increase in trust.

Physicians, however, have great trust in their fellow clinicians.

In the survey of 600 physicians, 94% said they trust doctors within their practice; 85% trusted doctors outside of their practice; and 89% trusted nurses. That trust increased during the pandemic, with 41% saying their trust in fellow physicians rose and 37% saying their trust in nurses did.

In a separate survey, NORC asked patients about their trust in various aspects of health care. Among 2,069 respondents, a wide majority reported that they trust doctors (84%) and nurses (85%), but only 64% trusted the health care system as a whole. One in three consumers (32%) said their trust in the health care system decreased during the pandemic, compared with 11% who said their trust increased.

The ABIM Foundation released the research findings on May 21 as part of Building Trust, a national campaign that aims to boost trust among patients, clinicians, system leaders, researchers, and others.

Richard J. Baron, MD, president and chief executive officer of the ABIM Foundation, said in an interview, “Clearly there’s lower trust in health care organization leaders and executives, and that’s troubling.

“Science by itself is not enough,” he said. “Becoming trustworthy has to be a core project of everybody in health care.”

Deterioration in physicians’ trust during the pandemic comes in part from failed promises of adequate personal protective equipment and some physicians’ loss of income as a result of the crisis, Dr. Baron said.

He added that the vaccine rollout was very uneven and that policies as to which elective procedures could be performed were handled differently in different parts of the country.

He also noted that, early on, transparency was lacking as to how many COVID patients hospitals were treating, which may have contributed to the decrease in trust in the system.
 

Fear of being known as ‘the COVID hospital’

Hospitals were afraid of being known as “the COVID hospital” and losing patients who were afraid to come there, Dr. Baron said.

He said the COVID-19 epidemic exacerbated problems regarding trust, but that trust has been declining for some time. The Building Trust campaign will focus on solutions in breaches of trust as physicians move increasingly toward being employees of huge systems, according to Dr. Baron.

However, trust works both ways, Dr. Baron notes. Physicians can be champions for their health care system or “throw the system under the bus,” he said.

For example, if a patient complains about the appointment system, clinicians who trust their institutions may say the system usually works and that they will try to make sure the patient has a better experience next time. Clinicians without trust may say they agree that the health care system doesn’t know what it is doing, and patients may further lose confidence when physicians validate their complaint, and patients may then go elsewhere.
 

78% of patients trust primary care doctor

When asked whether they trust their primary care physician, 78% of patients said yes. However, trust in doctors was higher among people who were older (90%), White (82%), or had high income (89%). Among people reporting lower trust, 25% said their physician spends too little time with them, and 14% said their doctor does not know or listen to them.

The survey shows that government agencies have work to do to earn trust. Responses indicate that 43% of physicians said they have “complete trust” in government health care agencies, such as the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention, which is substantially higher than other parts of the health care system. However, trust in agencies declined for 43% of physician respondents and increased for 21%.

Dhruv Khullar, MD, MPP, of the department of health policy and economics at Weill Cornell Medical College in New York, told this news organization the survey results match what he sees anecdotally in medicine – that physicians have been losing trust in the system but not in their colleagues.

He said the sample size of 600 is enough to be influential, though he said he would like to know the response rate, which was not calculated for this survey.

He added that, in large part, physicians’ lack of trust in their systems may come from generally being asked to see more patients and to meet more metrics during the same or shorter periods.

Physicians’ lack of trust in the system can have significant consequences, he said. It can lead to burnout, which has been linked with poorer quality of care and physician turnover, he noted.

COVID-19 led some physicians to wonder whether their system had their best interests at heart, insofar as access to adequate medicines and supplies as well as emotional support were inconsistent, Dr. Khullar said.

He said that to regain trust health care systems need to ask themselves questions in three areas. The first is whether their goals are focused on the best interest of the organization or the best interest of the patient.

“Next is competency,” Dr. Khullar said. “Maybe your motives are right, but are you able to deliver? Are you delivering a good product, whether clinical services or something else?”

The third area is transparency, he said. “Are you going to be honest and forthright in what we’re doing and where we’re going?”

Caroline Pearson, senior vice president of health care strategy for NORC, said the emailed survey was conducted between Dec. 29, 2020, and Feb. 5, 2021, with a health care survey partner that maintains a nationwide panel of physicians across specialties.

She said this report is fairly novel insofar as surveys are more typically conducted regarding patients’ trust of their doctors or of the health care system.

Ms. Pearson said because health care is delivered in teams, understanding the level of trust among the entities helps ensure that care will be delivered effectively and seamlessly with high quality.

“We want our patients to trust our doctors, but we really want doctors to trust each other and trust the hospitals and systems in which they’re working,” she said.

Dr. Baron, Ms. Pearson, and Dr. Khullar report no relevant financial relationships.

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

Physicians’ trust in health care system leaders has taken a steep drop during the COVID-19 pandemic, according to a survey conducted by NORC at the University of Chicago on behalf of the American Board of Internal Medicine Foundation.

Survey results, released May 21, indicate that 30% of physicians say their trust in the U.S. health care system and health care leadership has decreased during the pandemic. Only 18% reported an increase in trust.

Physicians, however, have great trust in their fellow clinicians.

In the survey of 600 physicians, 94% said they trust doctors within their practice; 85% trusted doctors outside of their practice; and 89% trusted nurses. That trust increased during the pandemic, with 41% saying their trust in fellow physicians rose and 37% saying their trust in nurses did.

In a separate survey, NORC asked patients about their trust in various aspects of health care. Among 2,069 respondents, a wide majority reported that they trust doctors (84%) and nurses (85%), but only 64% trusted the health care system as a whole. One in three consumers (32%) said their trust in the health care system decreased during the pandemic, compared with 11% who said their trust increased.

The ABIM Foundation released the research findings on May 21 as part of Building Trust, a national campaign that aims to boost trust among patients, clinicians, system leaders, researchers, and others.

Richard J. Baron, MD, president and chief executive officer of the ABIM Foundation, said in an interview, “Clearly there’s lower trust in health care organization leaders and executives, and that’s troubling.

“Science by itself is not enough,” he said. “Becoming trustworthy has to be a core project of everybody in health care.”

Deterioration in physicians’ trust during the pandemic comes in part from failed promises of adequate personal protective equipment and some physicians’ loss of income as a result of the crisis, Dr. Baron said.

He added that the vaccine rollout was very uneven and that policies as to which elective procedures could be performed were handled differently in different parts of the country.

He also noted that, early on, transparency was lacking as to how many COVID patients hospitals were treating, which may have contributed to the decrease in trust in the system.
 

Fear of being known as ‘the COVID hospital’

Hospitals were afraid of being known as “the COVID hospital” and losing patients who were afraid to come there, Dr. Baron said.

He said the COVID-19 epidemic exacerbated problems regarding trust, but that trust has been declining for some time. The Building Trust campaign will focus on solutions in breaches of trust as physicians move increasingly toward being employees of huge systems, according to Dr. Baron.

However, trust works both ways, Dr. Baron notes. Physicians can be champions for their health care system or “throw the system under the bus,” he said.

For example, if a patient complains about the appointment system, clinicians who trust their institutions may say the system usually works and that they will try to make sure the patient has a better experience next time. Clinicians without trust may say they agree that the health care system doesn’t know what it is doing, and patients may further lose confidence when physicians validate their complaint, and patients may then go elsewhere.
 

78% of patients trust primary care doctor

When asked whether they trust their primary care physician, 78% of patients said yes. However, trust in doctors was higher among people who were older (90%), White (82%), or had high income (89%). Among people reporting lower trust, 25% said their physician spends too little time with them, and 14% said their doctor does not know or listen to them.

The survey shows that government agencies have work to do to earn trust. Responses indicate that 43% of physicians said they have “complete trust” in government health care agencies, such as the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention, which is substantially higher than other parts of the health care system. However, trust in agencies declined for 43% of physician respondents and increased for 21%.

Dhruv Khullar, MD, MPP, of the department of health policy and economics at Weill Cornell Medical College in New York, told this news organization the survey results match what he sees anecdotally in medicine – that physicians have been losing trust in the system but not in their colleagues.

He said the sample size of 600 is enough to be influential, though he said he would like to know the response rate, which was not calculated for this survey.

He added that, in large part, physicians’ lack of trust in their systems may come from generally being asked to see more patients and to meet more metrics during the same or shorter periods.

Physicians’ lack of trust in the system can have significant consequences, he said. It can lead to burnout, which has been linked with poorer quality of care and physician turnover, he noted.

COVID-19 led some physicians to wonder whether their system had their best interests at heart, insofar as access to adequate medicines and supplies as well as emotional support were inconsistent, Dr. Khullar said.

He said that to regain trust health care systems need to ask themselves questions in three areas. The first is whether their goals are focused on the best interest of the organization or the best interest of the patient.

“Next is competency,” Dr. Khullar said. “Maybe your motives are right, but are you able to deliver? Are you delivering a good product, whether clinical services or something else?”

The third area is transparency, he said. “Are you going to be honest and forthright in what we’re doing and where we’re going?”

Caroline Pearson, senior vice president of health care strategy for NORC, said the emailed survey was conducted between Dec. 29, 2020, and Feb. 5, 2021, with a health care survey partner that maintains a nationwide panel of physicians across specialties.

She said this report is fairly novel insofar as surveys are more typically conducted regarding patients’ trust of their doctors or of the health care system.

Ms. Pearson said because health care is delivered in teams, understanding the level of trust among the entities helps ensure that care will be delivered effectively and seamlessly with high quality.

“We want our patients to trust our doctors, but we really want doctors to trust each other and trust the hospitals and systems in which they’re working,” she said.

Dr. Baron, Ms. Pearson, and Dr. Khullar report no relevant financial relationships.

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

Key clinical point: Among patients receiving liver transplantation for hepatocellular carcinoma (HCC), acute rejection conferred a significantly greater likelihood of HCC recurrence.

Major finding: HCC recurred in 28.6% of patients with acute rejections (defined as occurring within 20 months after transplant) vs 13.0% of patients without acute rejections (P = .002). Acute rejection remained a significant risk factor for recurrence in multivariable analysis (hazard ratio, 2.91).

Study details: Findings come from a retrospective study of 252 patients undergoing liver transplantation for HCC, of whom 91 had histopathologically confirmed acute rejections and 47 had HCC recurrence.

Disclosures: The researchers reported receiving funding for open access publications but no other financial support. The senior author disclosed ties to Merck Serono, Bayer AG, ERBE Elektromedizin, Amgen Inc, Johnson & Johnson, Takeda, Olympus K.K., Medtronic GmbH, and Intuitive Surg. Inc. The other researchers reported having no conflicts.

Source: Gül-Klein S et al. J Hepatocell Carcinoma. 2021 Mar 18. doi: 10.2147/JHC.S292010

Key clinical point: Among patients receiving liver transplantation for hepatocellular carcinoma (HCC), acute rejection conferred a significantly greater likelihood of HCC recurrence.

Major finding: HCC recurred in 28.6% of patients with acute rejections (defined as occurring within 20 months after transplant) vs 13.0% of patients without acute rejections (P = .002). Acute rejection remained a significant risk factor for recurrence in multivariable analysis (hazard ratio, 2.91).

Study details: Findings come from a retrospective study of 252 patients undergoing liver transplantation for HCC, of whom 91 had histopathologically confirmed acute rejections and 47 had HCC recurrence.

Disclosures: The researchers reported receiving funding for open access publications but no other financial support. The senior author disclosed ties to Merck Serono, Bayer AG, ERBE Elektromedizin, Amgen Inc, Johnson & Johnson, Takeda, Olympus K.K., Medtronic GmbH, and Intuitive Surg. Inc. The other researchers reported having no conflicts.

Source: Gül-Klein S et al. J Hepatocell Carcinoma. 2021 Mar 18. doi: 10.2147/JHC.S292010

Key clinical point: Among patients receiving liver transplantation for hepatocellular carcinoma (HCC), acute rejection conferred a significantly greater likelihood of HCC recurrence.

Major finding: HCC recurred in 28.6% of patients with acute rejections (defined as occurring within 20 months after transplant) vs 13.0% of patients without acute rejections (P = .002). Acute rejection remained a significant risk factor for recurrence in multivariable analysis (hazard ratio, 2.91).

Study details: Findings come from a retrospective study of 252 patients undergoing liver transplantation for HCC, of whom 91 had histopathologically confirmed acute rejections and 47 had HCC recurrence.

Disclosures: The researchers reported receiving funding for open access publications but no other financial support. The senior author disclosed ties to Merck Serono, Bayer AG, ERBE Elektromedizin, Amgen Inc, Johnson & Johnson, Takeda, Olympus K.K., Medtronic GmbH, and Intuitive Surg. Inc. The other researchers reported having no conflicts.

Source: Gül-Klein S et al. J Hepatocell Carcinoma. 2021 Mar 18. doi: 10.2147/JHC.S292010

Key clinical point: High serum levels of angiopoietin 2 (Ang2) levels identified patients with hepatocellular carcinoma (HCC) and predicted a shorter time to recurrence after treatment with curative intent.

Major finding: Serum Ang2 levels were significantly higher in patients with HCC vs controls (P less than .001) and patients with chronic liver disease (P less than .001). At the optimal threshold (3.5 ng/mL), sensitivity, specificity, and accuracy were 51%, 84%, and 59.5%, respectively. Higher serum Ang2 levels correlated with significantly shorter recurrence-free survival after ablation therapy, even after controlling for other prognostic factors.

Study details: The researchers reviewed medical charts and used sandwich enzyme-linked immunosorbent assay (ELISA) to measure Ang2 levels in stored serum from 275 patients with HCC, 98 patients with chronic liver disease, and 20 controls.

Disclosures: Partial funding came from the Japan Society for the Promotion of Science and the Program for Basic and Clinical Research on Hepatitis from Japan Agency for Medical Research and Development. The researchers reported having no conflicts of interest.

Source: J Ao et al. J Cancer. 2021 Mar 5. doi: 10.7150/jca.56436

Key clinical point: High serum levels of angiopoietin 2 (Ang2) levels identified patients with hepatocellular carcinoma (HCC) and predicted a shorter time to recurrence after treatment with curative intent.

Major finding: Serum Ang2 levels were significantly higher in patients with HCC vs controls (P less than .001) and patients with chronic liver disease (P less than .001). At the optimal threshold (3.5 ng/mL), sensitivity, specificity, and accuracy were 51%, 84%, and 59.5%, respectively. Higher serum Ang2 levels correlated with significantly shorter recurrence-free survival after ablation therapy, even after controlling for other prognostic factors.

Study details: The researchers reviewed medical charts and used sandwich enzyme-linked immunosorbent assay (ELISA) to measure Ang2 levels in stored serum from 275 patients with HCC, 98 patients with chronic liver disease, and 20 controls.

Disclosures: Partial funding came from the Japan Society for the Promotion of Science and the Program for Basic and Clinical Research on Hepatitis from Japan Agency for Medical Research and Development. The researchers reported having no conflicts of interest.

Source: J Ao et al. J Cancer. 2021 Mar 5. doi: 10.7150/jca.56436

Key clinical point: High serum levels of angiopoietin 2 (Ang2) levels identified patients with hepatocellular carcinoma (HCC) and predicted a shorter time to recurrence after treatment with curative intent.

Major finding: Serum Ang2 levels were significantly higher in patients with HCC vs controls (P less than .001) and patients with chronic liver disease (P less than .001). At the optimal threshold (3.5 ng/mL), sensitivity, specificity, and accuracy were 51%, 84%, and 59.5%, respectively. Higher serum Ang2 levels correlated with significantly shorter recurrence-free survival after ablation therapy, even after controlling for other prognostic factors.

Study details: The researchers reviewed medical charts and used sandwich enzyme-linked immunosorbent assay (ELISA) to measure Ang2 levels in stored serum from 275 patients with HCC, 98 patients with chronic liver disease, and 20 controls.

Disclosures: Partial funding came from the Japan Society for the Promotion of Science and the Program for Basic and Clinical Research on Hepatitis from Japan Agency for Medical Research and Development. The researchers reported having no conflicts of interest.

Source: J Ao et al. J Cancer. 2021 Mar 5. doi: 10.7150/jca.56436

Key clinical point: Among patients with hepatocellular carcinoma, overexpression of phosphatidylinositol glycan anchor biosynthesis, class C (PIGC) was linked to more aggressive disease and worse survival.

Major finding: PIGC mRNA was overexpressed in cancerous vs normal liver (P less than .0001). Among patients with liver cancer, higher PIGC expression correlated with worse overall survival (37.8 vs 71.0 months; hazard ratio [HR], 1.7, P = .003) and disease-free survival (48.4 vs 68.6 months; HR, 1.5, P = .007), and with higher tumor grade and stage, lymphatic metastasis, and TP53 mutation. In addition, liver cancer cell migration and proliferation were significantly higher in PIGC-upregulated cells, and significantly lower in PIGC-silenced cells. The PIGC mutation rate was 10%; PIGC mutation was significantly associated with higher T and M stages.

Study details: The researchers searched and analyzed bioinformatic databases and websites, such as UALCAN and cBioPortal , and performed Western blot, transwell migration assays, CCK-8 assays, and flow cytometry of cancerous and normal liver cells.

Disclosures: The Fundamental Research Funds of Wuhan University provided funding. The investigators reported having no conflicts of interest.

Source: Guo X et al. J Hepatocell Carcinoma. 2021 Apr 6. doi: 10.2147/JHC.S297601.
 

Key clinical point: Among patients with hepatocellular carcinoma, overexpression of phosphatidylinositol glycan anchor biosynthesis, class C (PIGC) was linked to more aggressive disease and worse survival.

Major finding: PIGC mRNA was overexpressed in cancerous vs normal liver (P less than .0001). Among patients with liver cancer, higher PIGC expression correlated with worse overall survival (37.8 vs 71.0 months; hazard ratio [HR], 1.7, P = .003) and disease-free survival (48.4 vs 68.6 months; HR, 1.5, P = .007), and with higher tumor grade and stage, lymphatic metastasis, and TP53 mutation. In addition, liver cancer cell migration and proliferation were significantly higher in PIGC-upregulated cells, and significantly lower in PIGC-silenced cells. The PIGC mutation rate was 10%; PIGC mutation was significantly associated with higher T and M stages.

Study details: The researchers searched and analyzed bioinformatic databases and websites, such as UALCAN and cBioPortal , and performed Western blot, transwell migration assays, CCK-8 assays, and flow cytometry of cancerous and normal liver cells.

Disclosures: The Fundamental Research Funds of Wuhan University provided funding. The investigators reported having no conflicts of interest.

Source: Guo X et al. J Hepatocell Carcinoma. 2021 Apr 6. doi: 10.2147/JHC.S297601.
 

Key clinical point: Among patients with hepatocellular carcinoma, overexpression of phosphatidylinositol glycan anchor biosynthesis, class C (PIGC) was linked to more aggressive disease and worse survival.

Major finding: PIGC mRNA was overexpressed in cancerous vs normal liver (P less than .0001). Among patients with liver cancer, higher PIGC expression correlated with worse overall survival (37.8 vs 71.0 months; hazard ratio [HR], 1.7, P = .003) and disease-free survival (48.4 vs 68.6 months; HR, 1.5, P = .007), and with higher tumor grade and stage, lymphatic metastasis, and TP53 mutation. In addition, liver cancer cell migration and proliferation were significantly higher in PIGC-upregulated cells, and significantly lower in PIGC-silenced cells. The PIGC mutation rate was 10%; PIGC mutation was significantly associated with higher T and M stages.

Study details: The researchers searched and analyzed bioinformatic databases and websites, such as UALCAN and cBioPortal , and performed Western blot, transwell migration assays, CCK-8 assays, and flow cytometry of cancerous and normal liver cells.

Disclosures: The Fundamental Research Funds of Wuhan University provided funding. The investigators reported having no conflicts of interest.

Source: Guo X et al. J Hepatocell Carcinoma. 2021 Apr 6. doi: 10.2147/JHC.S297601.
 

Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.

One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
 

Increased alcohol use after surgery

A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.

Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.

Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.

Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.

Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
 

Smoking and illicit drug use

Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.

One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.

These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.

The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.

The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.

Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.

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

Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.

One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
 

Increased alcohol use after surgery

A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.

Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.

Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.

Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.

Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
 

Smoking and illicit drug use

Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.

One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.

These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.

The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.

The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.

Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.

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

Internal medicine primarily affords us the skill to cope with disorders of chronicity that rarely disappear. For every pneumococcal pneumonia we eradicate, we have multiple patients with HIV who will be treated indefinitely. Diabetes, once a lethal disease, is now a chronic condition for most patients, and even with treatment the trajectory is usually one of progression.

One gratifying exception in my professional lifetime has been the introduction of gastric surgeries that reduce morbidity and seem to extend the life span of those who successfully undergo these procedures. The Roux-en-Y gastric bypass and sleeve gastrectomy have kept thousands of patients in better health for many years, giving them a second chance. For a subset, however, this second chance comes with a stumbling block of substance use – most notably alcohol – that exceeds their preoperative use.
 

Increased alcohol use after surgery

A group affiliated with the Department of Veterans Affairs (VA) recently reviewed the large central database to identify changes in alcohol consumption among patients who had undergone successful bariatric surgery. The VA regularly administers the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), a survey validated as a reliable estimate of individual alcohol consumption. It is inserted into the VA electronic health record where it can be readily retrieved. By matching these survey results with individuals who underwent bariatric surgery at the VA and survived at least 8 years post op, the authors were able to follow trends in alcohol consumption, beginning 2 years before surgery through 8 years after.

Using the same database, the authors identified a larger number of nonoperative control patients with slightly less obesity but otherwise matched for several elements of comorbidity, such as hypertension, certain psychiatric disorders, and personal habits, including alcohol consumption.

Alcohol use was categorized as none, minor social use, and “unhealthy” use. Among those with no or minor social use preoperatively, 4% converted to unhealthy use at 3 years and about 5% at 8 years, significantly more than in the nonoperative control group. Those who had gastric bypass had somewhat more conversion than did those who had sleeve gastrectomy, though not significantly so.

Patients with an alcohol concern preoperatively took an interesting course. Consumption declined from 2 years pre op to the year of surgery, suggesting that curtailing its use may have been a surgical precondition. Postoperatively, they returned to unhealthy drinking levels. Those who underwent the sleeve gastrectomy consumed about the same amount of alcohol as did their matched nonoperative controls, but those who underwent bypass increased their baseline unhealthy use beyond that of the controls.

Because total abstinence is often the recommendation for treating alcoholism, the research group assessed how adherent the excessive drinkers were to abstinence. In anticipation of surgery, the rates of abstinence increased until the year of surgery, but by 3 years post op, consumption was often up to unhealthy levels, though no more than that of control participants with preexisting drinking problems.
 

Smoking and illicit drug use

Although increased alcohol consumption has generated the most studies, some attention has been given to smoking and illicit drug use, which may also increase over time.

One small study looked at composite tobacco, alcohol, and drug use pre- and postoperatively over 2 years, using population data. The authors found a parallel pattern of users voluntarily reducing their substance use in anticipation of surgery but relapsing as the procedure made them more functional and perhaps more independent. Of the substances people resumed, alcohol by far involved the largest increase in use from the preoperative baseline.

These studies, as important as they are, reveal what happened more effectively than they disclose why it happened. The latter requires some clinical experience. Curtailing cigarettes and alcohol use preoperatively may have been done to stay in the good graces of the surgeon. Many patients may have seen this as their path to a second chance that they intended to maintain.

The incentive to proceed to surgical weight loss, which incurs a measure of risk and forces changes in long ingrained eating habits, involves avoiding future morbidity and promoting longevity. Thus, the postoperative behaviors that threaten the long-term goal need to become a component of ongoing follow-up.

The acquisition of adverse behaviors not present preoperatively seems more difficult to sort out, and obligates those of us following these patients to ask about changes in alcohol use and provide resources for them should they need intervention.

Dr. Plotzker is a retired endocrinologist with 40 years of experience treating patients in both private practice and hospital settings.

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

The Food and Drug Administration has approved the adjuvant use of nivolumab (Opdivo) in patients with resected esophageal or gastroesophageal junction (GEJ) cancer who have received neoadjuvant chemoradiotherapy and have residual pathological disease following surgery.

The approval addresses an unmet need among these patients, who have a high risk of recurrence but for whom surveillance is the only current management option after the above-described standard treatment, according to experts.

The FDA’s approval is based on results from the CheckMate 577 study, which showed a significant improvement in disease-free survival compared with placebo.

This was described as “a practice-changing trial in the treatment of esophageal cancer” by David H. Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, in an editorial in The New England Journal of Medicine that accompanied the published study results.

“The trial shows the first true advance in the adjuvant therapy of esophageal cancer in recent years,” wrote Dr. Ilson.

In the randomized, double-blind, phase 3 trial, patients with resected stage II or III esophageal or GEJ cancer were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by a dose of 480 mg every 4 weeks) or placebo. The maximum duration of the intervention period was 1 year.

All of these patients had received neoadjuvant chemoradiotherapy and had residual pathological disease, as noted in the new indication. Patients were enrolled regardless of programmed death ligand 1 (PD-L1) expression.

For the primary endpoint of disease-free survival, the median was 22.4 months for the nivolumab group (n = 532) versus 11.0 months for the placebo group (n = 262; hazard ratio [HR] for disease recurrence or death, 0.69; 96.4% confidence interval [CI], 0.56-0.86; P < .001).

The median follow-up was 24.4 months.

Disease-free survival favored nivolumab across multiple preplanned subgroups.

However, as Dr. Ilson noted in the editorial, the efficacy of nivolumab varied, with more benefit seen for patients with squamous cell cancer (HR, 0.61) than for those with adenocarcinoma (HR, 0.75). Patients with esophageal tumors also had greater benefit (HR, 0.61) than did those with GEJ tumors (HR, 0.87).

There was benefit in patients with node-negative disease (HR, 0.74) and node-positive disease (HR, 0.67) and benefit in patients with tumors that were PD-L1–negative (HR, 0.73) and PD-L1–positive (HR, 0.75).

There were fewer distant recurrences in the nivolumab group than in the placebo group (29% vs. 39%) and fewer locoregional recurrences (12% vs. 17%).

No new safety signals were observed, and 9% of the nivolumab patients discontinued the drug because of treatment-related adverse events versus 3% of placebo patients. In addition, a 1-year course of adjuvant nivolumab did not negatively impact patient-reported quality of life, the trialists reported.

Grade 3 or 4 adverse events of any cause were more frequent in the nivolumab group versus the placebo group (34% vs. 32%) as were those related to the intervention (13% vs. 6%).

Although overall survival data are not mature, “the doubling of median disease-free survival will almost certainly translate into an overall survival benefit,” Dr. Ilson wrote.

Notably, the trial’s original co-primary endpoint was overall survival, but was dropped to a secondary endpoint after enrollment “challenges.”

When the now-published data were first presented at the 2020 annual meeting of the European Society for Medical Oncology, the invited discussant, Andrés Cervantes, MD, PhD, University of Valencia, Spain, raised several issues with the trial.

Preoperative chemoradiation is not “universally accepted” as the standard of care in this setting, said Dr. Cervantes, president-elect of ESMO.

Dr. Ilson acknowledged as much. “A debate is ongoing about whether chemotherapy alone or combined chemoradiotherapy is the preferred treatment for esophageal cancer before surgery,” he wrote.

In addition, Dr. Cervantes noted that disease-free survival is not currently validated as a major endpoint in gastroesophageal cancers, and the median follow-up was short.

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

The Food and Drug Administration has approved the adjuvant use of nivolumab (Opdivo) in patients with resected esophageal or gastroesophageal junction (GEJ) cancer who have received neoadjuvant chemoradiotherapy and have residual pathological disease following surgery.

The approval addresses an unmet need among these patients, who have a high risk of recurrence but for whom surveillance is the only current management option after the above-described standard treatment, according to experts.

The FDA’s approval is based on results from the CheckMate 577 study, which showed a significant improvement in disease-free survival compared with placebo.

This was described as “a practice-changing trial in the treatment of esophageal cancer” by David H. Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, in an editorial in The New England Journal of Medicine that accompanied the published study results.

“The trial shows the first true advance in the adjuvant therapy of esophageal cancer in recent years,” wrote Dr. Ilson.

In the randomized, double-blind, phase 3 trial, patients with resected stage II or III esophageal or GEJ cancer were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by a dose of 480 mg every 4 weeks) or placebo. The maximum duration of the intervention period was 1 year.

All of these patients had received neoadjuvant chemoradiotherapy and had residual pathological disease, as noted in the new indication. Patients were enrolled regardless of programmed death ligand 1 (PD-L1) expression.

For the primary endpoint of disease-free survival, the median was 22.4 months for the nivolumab group (n = 532) versus 11.0 months for the placebo group (n = 262; hazard ratio [HR] for disease recurrence or death, 0.69; 96.4% confidence interval [CI], 0.56-0.86; P < .001).

The median follow-up was 24.4 months.

Disease-free survival favored nivolumab across multiple preplanned subgroups.

However, as Dr. Ilson noted in the editorial, the efficacy of nivolumab varied, with more benefit seen for patients with squamous cell cancer (HR, 0.61) than for those with adenocarcinoma (HR, 0.75). Patients with esophageal tumors also had greater benefit (HR, 0.61) than did those with GEJ tumors (HR, 0.87).

There was benefit in patients with node-negative disease (HR, 0.74) and node-positive disease (HR, 0.67) and benefit in patients with tumors that were PD-L1–negative (HR, 0.73) and PD-L1–positive (HR, 0.75).

There were fewer distant recurrences in the nivolumab group than in the placebo group (29% vs. 39%) and fewer locoregional recurrences (12% vs. 17%).

No new safety signals were observed, and 9% of the nivolumab patients discontinued the drug because of treatment-related adverse events versus 3% of placebo patients. In addition, a 1-year course of adjuvant nivolumab did not negatively impact patient-reported quality of life, the trialists reported.

Grade 3 or 4 adverse events of any cause were more frequent in the nivolumab group versus the placebo group (34% vs. 32%) as were those related to the intervention (13% vs. 6%).

Although overall survival data are not mature, “the doubling of median disease-free survival will almost certainly translate into an overall survival benefit,” Dr. Ilson wrote.

Notably, the trial’s original co-primary endpoint was overall survival, but was dropped to a secondary endpoint after enrollment “challenges.”

When the now-published data were first presented at the 2020 annual meeting of the European Society for Medical Oncology, the invited discussant, Andrés Cervantes, MD, PhD, University of Valencia, Spain, raised several issues with the trial.

Preoperative chemoradiation is not “universally accepted” as the standard of care in this setting, said Dr. Cervantes, president-elect of ESMO.

Dr. Ilson acknowledged as much. “A debate is ongoing about whether chemotherapy alone or combined chemoradiotherapy is the preferred treatment for esophageal cancer before surgery,” he wrote.

In addition, Dr. Cervantes noted that disease-free survival is not currently validated as a major endpoint in gastroesophageal cancers, and the median follow-up was short.

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

The Food and Drug Administration has approved the adjuvant use of nivolumab (Opdivo) in patients with resected esophageal or gastroesophageal junction (GEJ) cancer who have received neoadjuvant chemoradiotherapy and have residual pathological disease following surgery.

The approval addresses an unmet need among these patients, who have a high risk of recurrence but for whom surveillance is the only current management option after the above-described standard treatment, according to experts.

The FDA’s approval is based on results from the CheckMate 577 study, which showed a significant improvement in disease-free survival compared with placebo.

This was described as “a practice-changing trial in the treatment of esophageal cancer” by David H. Ilson, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, in an editorial in The New England Journal of Medicine that accompanied the published study results.

“The trial shows the first true advance in the adjuvant therapy of esophageal cancer in recent years,” wrote Dr. Ilson.

In the randomized, double-blind, phase 3 trial, patients with resected stage II or III esophageal or GEJ cancer were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by a dose of 480 mg every 4 weeks) or placebo. The maximum duration of the intervention period was 1 year.

All of these patients had received neoadjuvant chemoradiotherapy and had residual pathological disease, as noted in the new indication. Patients were enrolled regardless of programmed death ligand 1 (PD-L1) expression.

For the primary endpoint of disease-free survival, the median was 22.4 months for the nivolumab group (n = 532) versus 11.0 months for the placebo group (n = 262; hazard ratio [HR] for disease recurrence or death, 0.69; 96.4% confidence interval [CI], 0.56-0.86; P < .001).

The median follow-up was 24.4 months.

Disease-free survival favored nivolumab across multiple preplanned subgroups.

However, as Dr. Ilson noted in the editorial, the efficacy of nivolumab varied, with more benefit seen for patients with squamous cell cancer (HR, 0.61) than for those with adenocarcinoma (HR, 0.75). Patients with esophageal tumors also had greater benefit (HR, 0.61) than did those with GEJ tumors (HR, 0.87).

There was benefit in patients with node-negative disease (HR, 0.74) and node-positive disease (HR, 0.67) and benefit in patients with tumors that were PD-L1–negative (HR, 0.73) and PD-L1–positive (HR, 0.75).

There were fewer distant recurrences in the nivolumab group than in the placebo group (29% vs. 39%) and fewer locoregional recurrences (12% vs. 17%).

No new safety signals were observed, and 9% of the nivolumab patients discontinued the drug because of treatment-related adverse events versus 3% of placebo patients. In addition, a 1-year course of adjuvant nivolumab did not negatively impact patient-reported quality of life, the trialists reported.

Grade 3 or 4 adverse events of any cause were more frequent in the nivolumab group versus the placebo group (34% vs. 32%) as were those related to the intervention (13% vs. 6%).

Although overall survival data are not mature, “the doubling of median disease-free survival will almost certainly translate into an overall survival benefit,” Dr. Ilson wrote.

Notably, the trial’s original co-primary endpoint was overall survival, but was dropped to a secondary endpoint after enrollment “challenges.”

When the now-published data were first presented at the 2020 annual meeting of the European Society for Medical Oncology, the invited discussant, Andrés Cervantes, MD, PhD, University of Valencia, Spain, raised several issues with the trial.

Preoperative chemoradiation is not “universally accepted” as the standard of care in this setting, said Dr. Cervantes, president-elect of ESMO.

Dr. Ilson acknowledged as much. “A debate is ongoing about whether chemotherapy alone or combined chemoradiotherapy is the preferred treatment for esophageal cancer before surgery,” he wrote.

In addition, Dr. Cervantes noted that disease-free survival is not currently validated as a major endpoint in gastroesophageal cancers, and the median follow-up was short.

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

The greatest relative benefit from omecamtiv mecarbil, a member of the novel myotropic drug class that improves cardiac performance, is produced in heart failure patients with the lowest left ventricular ejection fraction (LVEF), a new analysis of the recently published phase 3 GALACTIC-HF trial has found.

The findings reinforce the potential for this drug to be helpful in the management of the most advanced stages of heart failure with reduced ejection fraction (HFrEF), reported John R. Teerlink, MD, director of heart failure at San Francisco Veterans Affairs Medical Center, at the annual scientific sessions of the American College of Cardiology.

The phase 3 multinational GALACTIC-HF trial, published earlier this year, linked omecamtiv mecarbil with an 8% reduction in the risk of a heart failure–related events or cardiovascular death, relative to placebo, which was the primary outcome. For entry, HFrEF patients were required to have a LVEF of 35% or less.

Drilling down on ejection fraction

The new analysis divided participants into quartiles of baseline LVEF and then compared relative outcomes and safety.

In the lowest quartile, defined by a LVEF of 22% or lower, the reduction in risk of events reached 17% (hazard ratio, 0.83; 95% confidence interval, 0.73-0.95) for omecamtiv mecarbil relative to placebo. In the highest, defined by a LVEF of 33% or greater, the benefit fell short of significance (HR 0.99; 95% CI, 0.84-1.16). Across quartiles, LVEF was the “strongest modifier of the treatment effect,” emerging in this analysis as a statistically significant (P = .004) continuous variable.

The comparison by LVEF quartiles also provided an opportunity to show that omecamtiv mecarbil was as safe and well tolerated in those with the most advanced disease as in those less sick. At the lowest levels of LVEF, like the higher levels, omecamtiv mecarbil did not produce any adverse effects on blood pressure, heart rate, potassium homeostasis, or renal function.

In GALACTIC-HF, 8,256 HFrEF patients with LVEF 35% or less were randomized to omecamtiv mecarbil or placebo. The primary composite outcome of hospitalization or urgent visit for heart failure or death from cardiovascular causes was evaluated after a median of 21.8 months on therapy.

When incidence rate per 100 patient years was graphed against the range of LVEF, the relative advantage of omecamtiv mecarbil became visible just below an LVEF of 30%, climbing steadily even to the lowest LVEF, which reached 10%.

Perhaps relevant to the reduction in events, there were also greater relative reductions in NT-proBNP (NT-proB-type natriuretic peptide) for omecamtiv mecarbil at lower relative to higher LVEF. Although omecamtiv mecarbil is not associated with any direct vascular, electrophysiologic, or neurohormonal effects, according to Dr. Teerlink, the indirect effects of selective binding to cardiac myosin has been associated with lower NT-proBNP and other biomarkers of cardiac remodeling in prior clinical studies.

Although Dr. Teerlink acknowledged that relatively few patients in GALACTIC-HF received an angiotensin-receptor neprilysin inhibitor (ARNI) or a sodium glucose cotransporter-2 (SGLT2) inhibitor, he said there is “every reason to believe that omecamtiv mecarbil would be complementary to these therapies.” He said the mechanism of action of omecamtiv mecarbil, which improves systolic function, has no overlap with these drugs.

Importantly, there is a particular need for new treatment options in patients with advanced LVEF, according to Dr. Teerlink, who cited evidence, for example, that “the beneficial effect of [the ARNI] sacubitril valsartan, while still significant, decreases in patients with LVEF less than 35%.”

Overall, based on these results, “we believe that omecamtiv mecarbil represents a novel therapy that holds the promise of improving clinical outcomes in patients with severely reduced ejection fraction, which are the very patients that are most challenging for us to treat,” Dr. Teerlink said.
 

Omecamtiv mecarbil may ‘buy you some time’

Ileana Piña, MD, clinical professor of medicine, Central Michigan University, Mount Pleasant, Mich., agreed. She said that omecamtiv mecarbil, if approved, will be an option for the type of HFrEF patients who are being considered for heart transplant or mechanical-assist devices.

“We are very loath to use inotropes in this population, because we know that ultimately the inotrope is not going to do well,” said Dr. Piña, calling these therapies a “Band-Aid.” Based on the evidence from GALACTIC-HF, she thinks that omecamtiv mecarbil will be more versatile.

“This drug does not increase myocardial oxygen demand as do the inotropes, and it can be given in the outpatient setting if need be, so I see this as a real advance,” Dr. Piña said. Although Dr. Piña acknowledged that omecamtiv mecarbil did not reduce mortality in the GALACTIC-HF trial, “at least it will buy you some time.”

Dr. Teerlink has financial relationships with multiple pharmaceutical companies, including Amgen, Cytogenetics, and Servier, which provided funding for the GALACTIC-HF trial. Dr. Piña reports no potential conflicts of interest.

The greatest relative benefit from omecamtiv mecarbil, a member of the novel myotropic drug class that improves cardiac performance, is produced in heart failure patients with the lowest left ventricular ejection fraction (LVEF), a new analysis of the recently published phase 3 GALACTIC-HF trial has found.

The findings reinforce the potential for this drug to be helpful in the management of the most advanced stages of heart failure with reduced ejection fraction (HFrEF), reported John R. Teerlink, MD, director of heart failure at San Francisco Veterans Affairs Medical Center, at the annual scientific sessions of the American College of Cardiology.

The phase 3 multinational GALACTIC-HF trial, published earlier this year, linked omecamtiv mecarbil with an 8% reduction in the risk of a heart failure–related events or cardiovascular death, relative to placebo, which was the primary outcome. For entry, HFrEF patients were required to have a LVEF of 35% or less.

Drilling down on ejection fraction

The new analysis divided participants into quartiles of baseline LVEF and then compared relative outcomes and safety.

In the lowest quartile, defined by a LVEF of 22% or lower, the reduction in risk of events reached 17% (hazard ratio, 0.83; 95% confidence interval, 0.73-0.95) for omecamtiv mecarbil relative to placebo. In the highest, defined by a LVEF of 33% or greater, the benefit fell short of significance (HR 0.99; 95% CI, 0.84-1.16). Across quartiles, LVEF was the “strongest modifier of the treatment effect,” emerging in this analysis as a statistically significant (P = .004) continuous variable.

The comparison by LVEF quartiles also provided an opportunity to show that omecamtiv mecarbil was as safe and well tolerated in those with the most advanced disease as in those less sick. At the lowest levels of LVEF, like the higher levels, omecamtiv mecarbil did not produce any adverse effects on blood pressure, heart rate, potassium homeostasis, or renal function.

In GALACTIC-HF, 8,256 HFrEF patients with LVEF 35% or less were randomized to omecamtiv mecarbil or placebo. The primary composite outcome of hospitalization or urgent visit for heart failure or death from cardiovascular causes was evaluated after a median of 21.8 months on therapy.

When incidence rate per 100 patient years was graphed against the range of LVEF, the relative advantage of omecamtiv mecarbil became visible just below an LVEF of 30%, climbing steadily even to the lowest LVEF, which reached 10%.

Perhaps relevant to the reduction in events, there were also greater relative reductions in NT-proBNP (NT-proB-type natriuretic peptide) for omecamtiv mecarbil at lower relative to higher LVEF. Although omecamtiv mecarbil is not associated with any direct vascular, electrophysiologic, or neurohormonal effects, according to Dr. Teerlink, the indirect effects of selective binding to cardiac myosin has been associated with lower NT-proBNP and other biomarkers of cardiac remodeling in prior clinical studies.

Although Dr. Teerlink acknowledged that relatively few patients in GALACTIC-HF received an angiotensin-receptor neprilysin inhibitor (ARNI) or a sodium glucose cotransporter-2 (SGLT2) inhibitor, he said there is “every reason to believe that omecamtiv mecarbil would be complementary to these therapies.” He said the mechanism of action of omecamtiv mecarbil, which improves systolic function, has no overlap with these drugs.

Importantly, there is a particular need for new treatment options in patients with advanced LVEF, according to Dr. Teerlink, who cited evidence, for example, that “the beneficial effect of [the ARNI] sacubitril valsartan, while still significant, decreases in patients with LVEF less than 35%.”

Overall, based on these results, “we believe that omecamtiv mecarbil represents a novel therapy that holds the promise of improving clinical outcomes in patients with severely reduced ejection fraction, which are the very patients that are most challenging for us to treat,” Dr. Teerlink said.
 

Omecamtiv mecarbil may ‘buy you some time’

Ileana Piña, MD, clinical professor of medicine, Central Michigan University, Mount Pleasant, Mich., agreed. She said that omecamtiv mecarbil, if approved, will be an option for the type of HFrEF patients who are being considered for heart transplant or mechanical-assist devices.

“We are very loath to use inotropes in this population, because we know that ultimately the inotrope is not going to do well,” said Dr. Piña, calling these therapies a “Band-Aid.” Based on the evidence from GALACTIC-HF, she thinks that omecamtiv mecarbil will be more versatile.

“This drug does not increase myocardial oxygen demand as do the inotropes, and it can be given in the outpatient setting if need be, so I see this as a real advance,” Dr. Piña said. Although Dr. Piña acknowledged that omecamtiv mecarbil did not reduce mortality in the GALACTIC-HF trial, “at least it will buy you some time.”

Dr. Teerlink has financial relationships with multiple pharmaceutical companies, including Amgen, Cytogenetics, and Servier, which provided funding for the GALACTIC-HF trial. Dr. Piña reports no potential conflicts of interest.

The greatest relative benefit from omecamtiv mecarbil, a member of the novel myotropic drug class that improves cardiac performance, is produced in heart failure patients with the lowest left ventricular ejection fraction (LVEF), a new analysis of the recently published phase 3 GALACTIC-HF trial has found.

The findings reinforce the potential for this drug to be helpful in the management of the most advanced stages of heart failure with reduced ejection fraction (HFrEF), reported John R. Teerlink, MD, director of heart failure at San Francisco Veterans Affairs Medical Center, at the annual scientific sessions of the American College of Cardiology.

The phase 3 multinational GALACTIC-HF trial, published earlier this year, linked omecamtiv mecarbil with an 8% reduction in the risk of a heart failure–related events or cardiovascular death, relative to placebo, which was the primary outcome. For entry, HFrEF patients were required to have a LVEF of 35% or less.

Drilling down on ejection fraction

The new analysis divided participants into quartiles of baseline LVEF and then compared relative outcomes and safety.

In the lowest quartile, defined by a LVEF of 22% or lower, the reduction in risk of events reached 17% (hazard ratio, 0.83; 95% confidence interval, 0.73-0.95) for omecamtiv mecarbil relative to placebo. In the highest, defined by a LVEF of 33% or greater, the benefit fell short of significance (HR 0.99; 95% CI, 0.84-1.16). Across quartiles, LVEF was the “strongest modifier of the treatment effect,” emerging in this analysis as a statistically significant (P = .004) continuous variable.

The comparison by LVEF quartiles also provided an opportunity to show that omecamtiv mecarbil was as safe and well tolerated in those with the most advanced disease as in those less sick. At the lowest levels of LVEF, like the higher levels, omecamtiv mecarbil did not produce any adverse effects on blood pressure, heart rate, potassium homeostasis, or renal function.

In GALACTIC-HF, 8,256 HFrEF patients with LVEF 35% or less were randomized to omecamtiv mecarbil or placebo. The primary composite outcome of hospitalization or urgent visit for heart failure or death from cardiovascular causes was evaluated after a median of 21.8 months on therapy.

When incidence rate per 100 patient years was graphed against the range of LVEF, the relative advantage of omecamtiv mecarbil became visible just below an LVEF of 30%, climbing steadily even to the lowest LVEF, which reached 10%.

Perhaps relevant to the reduction in events, there were also greater relative reductions in NT-proBNP (NT-proB-type natriuretic peptide) for omecamtiv mecarbil at lower relative to higher LVEF. Although omecamtiv mecarbil is not associated with any direct vascular, electrophysiologic, or neurohormonal effects, according to Dr. Teerlink, the indirect effects of selective binding to cardiac myosin has been associated with lower NT-proBNP and other biomarkers of cardiac remodeling in prior clinical studies.

Although Dr. Teerlink acknowledged that relatively few patients in GALACTIC-HF received an angiotensin-receptor neprilysin inhibitor (ARNI) or a sodium glucose cotransporter-2 (SGLT2) inhibitor, he said there is “every reason to believe that omecamtiv mecarbil would be complementary to these therapies.” He said the mechanism of action of omecamtiv mecarbil, which improves systolic function, has no overlap with these drugs.

Importantly, there is a particular need for new treatment options in patients with advanced LVEF, according to Dr. Teerlink, who cited evidence, for example, that “the beneficial effect of [the ARNI] sacubitril valsartan, while still significant, decreases in patients with LVEF less than 35%.”

Overall, based on these results, “we believe that omecamtiv mecarbil represents a novel therapy that holds the promise of improving clinical outcomes in patients with severely reduced ejection fraction, which are the very patients that are most challenging for us to treat,” Dr. Teerlink said.
 

Omecamtiv mecarbil may ‘buy you some time’

Ileana Piña, MD, clinical professor of medicine, Central Michigan University, Mount Pleasant, Mich., agreed. She said that omecamtiv mecarbil, if approved, will be an option for the type of HFrEF patients who are being considered for heart transplant or mechanical-assist devices.

“We are very loath to use inotropes in this population, because we know that ultimately the inotrope is not going to do well,” said Dr. Piña, calling these therapies a “Band-Aid.” Based on the evidence from GALACTIC-HF, she thinks that omecamtiv mecarbil will be more versatile.

“This drug does not increase myocardial oxygen demand as do the inotropes, and it can be given in the outpatient setting if need be, so I see this as a real advance,” Dr. Piña said. Although Dr. Piña acknowledged that omecamtiv mecarbil did not reduce mortality in the GALACTIC-HF trial, “at least it will buy you some time.”

Dr. Teerlink has financial relationships with multiple pharmaceutical companies, including Amgen, Cytogenetics, and Servier, which provided funding for the GALACTIC-HF trial. Dr. Piña reports no potential conflicts of interest.

It’s now official: The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST-WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions. A follow-up report during the annual scientific sessions of the American College of Cardiology fleshed out the evidence and firmed up their landmark conclusion.

The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure.

Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting.
 

Equally effective ‘across the full range of LVEFs.’

Perhaps as notable and unprecedented was the further finding that the clinical benefits seen with treatment of patients with type 2 diabetes with sotagliflozin was consistent regardless of the ejection fraction they had at entry. Enrolled patients with baseline LVEFs in the range of 25% received a relative benefit from sotagliflozin treatment that was statistically no different from the benefit seen in patients who entered with an LVEF in the neighborhood of 45%, 65%, or at any other level across the LVEF spectrum, a finding that Dr. Bhatt called “remarkable” during a press briefing. “The results show the benefit of sotagliflozin across the full range of LVEFs.”

“We are very excited in the heart failure world by the SGLT2 inhibitors; we’ve been impressed by their reduction in heart failure hospitalizations, but we wonder about the patients with HFpEF, where we haven’t had a blockbuster drug to give,” said Ileana L. Piña, MD, a heart failure specialist and medical officer with the Food and Drug Administration.

The new findings “look like they could pose a regulatory indication [for sotagliflozin] for patients with type 2 diabetes and heart failure across the entire spectrum of heart failure,” said Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart & Vascular institute in Falls Church, Va., and designated discussant for Dr. Bhatt’s report.

A significant on-treatment reduction in CV death

Other new, notable findings from the meta-analysis included the observation that while treatment with sotagliflozin failed to produce a significant reduction in cardiovascular death, compared with placebo, in the intent-to-treat analysis of all patients and of those with heart failure at baseline (it produced nonsignificant point-estimate reductions of 11% compared with placebo for all patients, and of 23% for patients who began the study with heart failure), it did result in a significant 23% relative risk reduction when the researchers focused on patients while they remained adherent to their sotagliflozin regimen (the on-treatment analysis). This 23% relative reduction appeared among all enrolled patients, as well as in the subgroup that started with diagnosed heart failure.

“Given the totality of data from the SGLT2 inhibitors, I think this is a real finding,” Dr. Bhatt said.

Additional analyses also showed that, among women, treatment with sotagliflozin was linked with significant relative reductions in the primary endpoint of roughly 30% compared with placebo among all patients, and also among those with heart failure at baseline. “HFpEF is a problem particularly in older women, and we showed that the benefit was consistent in men and women,” Dr. Bhatt said.

He acknowledged that results are expected soon from two pivotal trials that are examining two different SGLT2 inhibitors, dapagliflozin and empagliflozin, in patients with HFpEF. “I think there will be a class effect for both SGLT2 inhibitors and sotagliflozin for reducing heart failure events in patients with HFpEF, and I predict that the dapagliflozin and empagliflozin trials will have positive results,” Dr. Bhatt said.

Sotagliflozin differs from the SGLT2 inhibitors by also inhibiting SGLT1, an enzyme found in the gastrointestinal system that, when inhibited, results in increased glucose excretion from the gut and a cut in bloodstream levels of postprandial glucose levels. The Food and Drug Administration accepted data from SCORED and SOLOIST-WHF as part of the evidence the agency is now considering for granting a new drug approval to sotagliflozin.

SCORED and SOLOIST-WHF were initially sponsored by Sanofi, and later by Lexicon Pharmaceuticals. Dr. Bhatt’s institution, Brigham and Women’s Hospital, has received funding from Sanofi and Lexicon Pharmaceuticals. He has been a consultant to and received honoraria from K₂P, Level Ex, and MJH Life Sciences; he has been an adviser to Cardax, Cereno Scientific, Myokardia, Novo Nordisk, Phase Bio, and PLx Pharma; and he has received research funding from numerous companies. Dr. Piña has no relevant disclosures. Dr. O’Connor has been a consultant to Arena, Bayer, Bristol-Myers Squibb, Merck, and Windtree, and he has an ownership interest in Biscardia.

[email protected]

It’s now official: The investigational sodium-glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin is the first agent clearly shown in a prespecified analysis of randomized trials to improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFpEF).

Researchers who ran the SCORED and SOLOIST-WHF pivotal trials for sotagliflozin first made that claim in November 2020 when reporting top-line results from a prespecified meta-analysis of the two trials during the American Heart Association annual scientific sessions. A follow-up report during the annual scientific sessions of the American College of Cardiology fleshed out the evidence and firmed up their landmark conclusion.

The meta-analysis (Abstract 410-08) included 4,500 patients with type 2 diabetes and diagnosed heart failure at entry; its primary endpoint, which was the same in both trials, was the combined incidence of cardiovascular death and the total number of either hospitalization for heart failure or urgent outpatient visits for heart failure.

Compared with placebo, treatment with sotagliflozin for a median of about 15 months dropped this composite endpoint by a relative 33% among the 1,931 who began the study with a left ventricular ejection fraction (LVEF) of at least 50% (HFpEF), by a relative 22% in the 1,758 patients who entered with an LVEF of less than 40% (patients with heart failure with reduced ejection fraction), and by a relative 43% among the 811 patients who began with an LVEF of 40%-49% (patients with heart failure with mid-range ejection fraction). The relative risk reductions were significant for all three subgroups, Deepak L. Bhatt, MD, reported at the meeting.
 

Equally effective ‘across the full range of LVEFs.’

Perhaps as notable and unprecedented was the further finding that the clinical benefits seen with treatment of patients with type 2 diabetes with sotagliflozin was consistent regardless of the ejection fraction they had at entry. Enrolled patients with baseline LVEFs in the range of 25% received a relative benefit from sotagliflozin treatment that was statistically no different from the benefit seen in patients who entered with an LVEF in the neighborhood of 45%, 65%, or at any other level across the LVEF spectrum, a finding that Dr. Bhatt called “remarkable” during a press briefing. “The results show the benefit of sotagliflozin across the full range of LVEFs.”

“We are very excited in the heart failure world by the SGLT2 inhibitors; we’ve been impressed by their reduction in heart failure hospitalizations, but we wonder about the patients with HFpEF, where we haven’t had a blockbuster drug to give,” said Ileana L. Piña, MD, a heart failure specialist and medical officer with the Food and Drug Administration.

The new findings “look like they could pose a regulatory indication [for sotagliflozin] for patients with type 2 diabetes and heart failure across the entire spectrum of heart failure,” said Christopher M. O’Connor, MD, a heart failure specialist and president of the Inova Heart & Vascular institute in Falls Church, Va., and designated discussant for Dr. Bhatt’s report.