Federal Practitioner

The results of a phase 2 clinical trial of durvalumab with add-on therapies oleclumab or monalizumab, suggest this novel combination may prove beneficial in patients with unresectable stage 3 non–small-cell lung cancer.

Combinations of the PD-L1 inhibitor durvalumab (Imfinzi, AstraZeneca) with the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab led to improved overall response rate and progression-free survival compared to durvalumab alone.

The findings support further study in a phase 3 clinical trial, according to the authors of the study recently published in the Journal of Clinical Oncology.

Durvalumab is the standard treatment following consolidation therapy of chemoradiotherapy in unresectable stage 3 non–small-cell lung cancer (NSCLC). Although it extended progression-free survival (PFS) and overall survival in the PACIFIC phase 3 study, some patients experience a recurrence, which has led to exploration of immunotherapy combinations.

Oleclumab inhibits the enzyme CD73, found on the surfaces of both tumor and immune cells. Its activity leads to an immunosuppressive effect in the tumor microenvironment, and preclinical studies have shown that it can have an additive antitumor effect when combined with PD-1 or PD-L1 inhibitors. A phase 1 study also suggested efficacy. Monalizumab blocks interactions between major histocompatibility complex-E (HLA-E) and an inhibitor receptor. A number of tumors overexpress HLA-E, triggering inhibitor signals that inhibit natural killer and CD8+ T cells.

“COAST was an interesting study that, although not definitive, suggested that the combination of durvalumab with oleclumab or with monalizumab was more effective than durvalumab alone in the consolidation setting after definitive concurrent chemoradiation for patients with stage 3 unresectable NSCLC,” said Nathan Pennell, MD, PhD, who wrote an accompanying editorial.

Despite the positive signal, Dr. Pennell expressed some skepticism that the combinations would pass a phase 3 test. He questioned the choice of response rate as the primary endpoint of the phase 2 study, and noted that the durvalumab arm had worse progression-free survival (PFS) than the previous PACIFIC trial. It could be that the clinical characteristics of the study population differed between the two trials, in which case the improved objective response rate (ORR) and PFS results should be encouraging. It’s also possible the COAST trial’s small sample size led to a mismatch between the control and treatment group despite randomization, in which case the findings may not be valid.

“These are the kinds of issues that keep drug developers up at night. There really is no way to know which scenario is correct without doing the larger trial. I do hope though that the phase 3 trials have robust biomarker analysis including PDL1 to make sure the arms are as well matched for known prognostic and predictive markers as possible,” said Dr. Pennell, who is vice chair of clinical research at Taussig Cancer Institute.
 

The study details

The researchers randomized 189 patients to durvalumab, durvalumab plus oleclumab, or durvalumab plus monalizumab between January 2019 and July 2020. After a median follow-up of 11.5 months, there was a higher confirmed objective response rate in the durvalumab plus oleclumab group (30.0%; 95% confidence interval, 18.8%-43.2%) and the durvalumab plus monalizumab group (35.5%; 95% CI, 23.7%-48.7%) versus durvalumab alone (17.9%; 95% CI, 9.6%-29.2%).

Compared to durvalumab alone, there was improved PFS in both durvalumab plus oleclumab (stratified hazard ratio, 0.44; 95% CI, 0.26-0.75) and durvalumab plus monalizumab (HR, 0.42; 95% CI, 0.24-0.72). At 12 months, PFS was 62.6% (95% CI, 48.1-74.2%) for durvalumab plus oleclumab, 72.7% (95% CI, 58.8-82.6%) for durvalumab plus monalizumab, and 33.9% (95% CI, 21.2-47.1%) for durvalumab alone.

The study was funded by AstraZeneca.

The results of a phase 2 clinical trial of durvalumab with add-on therapies oleclumab or monalizumab, suggest this novel combination may prove beneficial in patients with unresectable stage 3 non–small-cell lung cancer.

Combinations of the PD-L1 inhibitor durvalumab (Imfinzi, AstraZeneca) with the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab led to improved overall response rate and progression-free survival compared to durvalumab alone.

The findings support further study in a phase 3 clinical trial, according to the authors of the study recently published in the Journal of Clinical Oncology.

Durvalumab is the standard treatment following consolidation therapy of chemoradiotherapy in unresectable stage 3 non–small-cell lung cancer (NSCLC). Although it extended progression-free survival (PFS) and overall survival in the PACIFIC phase 3 study, some patients experience a recurrence, which has led to exploration of immunotherapy combinations.

Oleclumab inhibits the enzyme CD73, found on the surfaces of both tumor and immune cells. Its activity leads to an immunosuppressive effect in the tumor microenvironment, and preclinical studies have shown that it can have an additive antitumor effect when combined with PD-1 or PD-L1 inhibitors. A phase 1 study also suggested efficacy. Monalizumab blocks interactions between major histocompatibility complex-E (HLA-E) and an inhibitor receptor. A number of tumors overexpress HLA-E, triggering inhibitor signals that inhibit natural killer and CD8+ T cells.

“COAST was an interesting study that, although not definitive, suggested that the combination of durvalumab with oleclumab or with monalizumab was more effective than durvalumab alone in the consolidation setting after definitive concurrent chemoradiation for patients with stage 3 unresectable NSCLC,” said Nathan Pennell, MD, PhD, who wrote an accompanying editorial.

Despite the positive signal, Dr. Pennell expressed some skepticism that the combinations would pass a phase 3 test. He questioned the choice of response rate as the primary endpoint of the phase 2 study, and noted that the durvalumab arm had worse progression-free survival (PFS) than the previous PACIFIC trial. It could be that the clinical characteristics of the study population differed between the two trials, in which case the improved objective response rate (ORR) and PFS results should be encouraging. It’s also possible the COAST trial’s small sample size led to a mismatch between the control and treatment group despite randomization, in which case the findings may not be valid.

“These are the kinds of issues that keep drug developers up at night. There really is no way to know which scenario is correct without doing the larger trial. I do hope though that the phase 3 trials have robust biomarker analysis including PDL1 to make sure the arms are as well matched for known prognostic and predictive markers as possible,” said Dr. Pennell, who is vice chair of clinical research at Taussig Cancer Institute.
 

The study details

The researchers randomized 189 patients to durvalumab, durvalumab plus oleclumab, or durvalumab plus monalizumab between January 2019 and July 2020. After a median follow-up of 11.5 months, there was a higher confirmed objective response rate in the durvalumab plus oleclumab group (30.0%; 95% confidence interval, 18.8%-43.2%) and the durvalumab plus monalizumab group (35.5%; 95% CI, 23.7%-48.7%) versus durvalumab alone (17.9%; 95% CI, 9.6%-29.2%).

Compared to durvalumab alone, there was improved PFS in both durvalumab plus oleclumab (stratified hazard ratio, 0.44; 95% CI, 0.26-0.75) and durvalumab plus monalizumab (HR, 0.42; 95% CI, 0.24-0.72). At 12 months, PFS was 62.6% (95% CI, 48.1-74.2%) for durvalumab plus oleclumab, 72.7% (95% CI, 58.8-82.6%) for durvalumab plus monalizumab, and 33.9% (95% CI, 21.2-47.1%) for durvalumab alone.

The study was funded by AstraZeneca.

The results of a phase 2 clinical trial of durvalumab with add-on therapies oleclumab or monalizumab, suggest this novel combination may prove beneficial in patients with unresectable stage 3 non–small-cell lung cancer.

Combinations of the PD-L1 inhibitor durvalumab (Imfinzi, AstraZeneca) with the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab led to improved overall response rate and progression-free survival compared to durvalumab alone.

The findings support further study in a phase 3 clinical trial, according to the authors of the study recently published in the Journal of Clinical Oncology.

Durvalumab is the standard treatment following consolidation therapy of chemoradiotherapy in unresectable stage 3 non–small-cell lung cancer (NSCLC). Although it extended progression-free survival (PFS) and overall survival in the PACIFIC phase 3 study, some patients experience a recurrence, which has led to exploration of immunotherapy combinations.

Oleclumab inhibits the enzyme CD73, found on the surfaces of both tumor and immune cells. Its activity leads to an immunosuppressive effect in the tumor microenvironment, and preclinical studies have shown that it can have an additive antitumor effect when combined with PD-1 or PD-L1 inhibitors. A phase 1 study also suggested efficacy. Monalizumab blocks interactions between major histocompatibility complex-E (HLA-E) and an inhibitor receptor. A number of tumors overexpress HLA-E, triggering inhibitor signals that inhibit natural killer and CD8+ T cells.

“COAST was an interesting study that, although not definitive, suggested that the combination of durvalumab with oleclumab or with monalizumab was more effective than durvalumab alone in the consolidation setting after definitive concurrent chemoradiation for patients with stage 3 unresectable NSCLC,” said Nathan Pennell, MD, PhD, who wrote an accompanying editorial.

Despite the positive signal, Dr. Pennell expressed some skepticism that the combinations would pass a phase 3 test. He questioned the choice of response rate as the primary endpoint of the phase 2 study, and noted that the durvalumab arm had worse progression-free survival (PFS) than the previous PACIFIC trial. It could be that the clinical characteristics of the study population differed between the two trials, in which case the improved objective response rate (ORR) and PFS results should be encouraging. It’s also possible the COAST trial’s small sample size led to a mismatch between the control and treatment group despite randomization, in which case the findings may not be valid.

“These are the kinds of issues that keep drug developers up at night. There really is no way to know which scenario is correct without doing the larger trial. I do hope though that the phase 3 trials have robust biomarker analysis including PDL1 to make sure the arms are as well matched for known prognostic and predictive markers as possible,” said Dr. Pennell, who is vice chair of clinical research at Taussig Cancer Institute.
 

The study details

The researchers randomized 189 patients to durvalumab, durvalumab plus oleclumab, or durvalumab plus monalizumab between January 2019 and July 2020. After a median follow-up of 11.5 months, there was a higher confirmed objective response rate in the durvalumab plus oleclumab group (30.0%; 95% confidence interval, 18.8%-43.2%) and the durvalumab plus monalizumab group (35.5%; 95% CI, 23.7%-48.7%) versus durvalumab alone (17.9%; 95% CI, 9.6%-29.2%).

Compared to durvalumab alone, there was improved PFS in both durvalumab plus oleclumab (stratified hazard ratio, 0.44; 95% CI, 0.26-0.75) and durvalumab plus monalizumab (HR, 0.42; 95% CI, 0.24-0.72). At 12 months, PFS was 62.6% (95% CI, 48.1-74.2%) for durvalumab plus oleclumab, 72.7% (95% CI, 58.8-82.6%) for durvalumab plus monalizumab, and 33.9% (95% CI, 21.2-47.1%) for durvalumab alone.

The study was funded by AstraZeneca.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

MONTREAL – Patients who discontinue levothyroxine for subclinical hypothyroidism may gravitate towards becoming mildly hypothyroid again, but they importantly show no differences in terms of symptoms and quality of life – and sometimes show even improvement – compared with those who continue treatment, new research shows.

“Our results show feasibility of patient enrollment and safety of discontinuing levothyroxine in patients with subclinical hypothyroidism,” said first author Spyridoula Maraka, MD, when presenting the findings at the American Thyroid Association annual meeting.

Recommendations against levothyroxine for subclinical hypothyroidism

Subclinical hypothyroidism is commonly over-diagnosed, and treatment with thyroid hormone replacement, levothyroxine, has been shown to provide little, if any, benefit in terms of quality of life or relief of thyroid-related symptoms for these patients.

The treatment is meanwhile associated with burdens including cost and lifestyle adjustments, and one guideline panel recently issued a strong recommendation against routine levothyroxine use in most adults with subclinical hypothyroidism.

Nevertheless, levothyroxine treatment has soared in popularity and become one of the most commonly prescribed drugs in the United States.

With research lacking on one key solution of discontinuation of the therapy, Dr. Maraka, who is part of the Division of Endocrinology and Metabolism at the University of Arkansas for Medical Sciences, Little Rock, and colleagues conducted a double-blind, placebo-controlled trial at the Central Arkansas Veterans Healthcare System. In total, 50 patients treated for subclinical hypothyroidism were randomized 1:1 to continue receiving levothyroxine (25-75 mcg daily) or to discontinue treatment and receive a placebo instead, with a planned 6-month follow-up.

In the current interim analysis, Dr. Maraka reported results for the first 40 patients, including 20 randomized to levothyroxine and 20 to discontinuation.

There were no significant differences between the discontinuation and levothyroxine groups at baseline, which were of a similar age (66.2 vs. 70.8 years) and gender (75% women vs. 85% men).

The groups had similar baseline thyroid-stimulating hormone (TSH) levels (3.0 vs. 2.6 mIU/L), free T4 (both 0.9 ng/dL), thyroid peroxidase antibody positivity (17% vs. 11%), and similar clinical symptoms. All patients had at least one elevated TSH reading prior to starting levothyroxine.

With a follow-up of 6-8 weeks, 36.8% of patients in the discontinuation group had subclinical hypothyroidism, compared with 10% of patients who remained on levothyroxine (P = .0648), TSH levels were 5.5 versus 2.7 mIU/L (P = .001) and free T4 levels were 0.8 versus 0.9 ng/dL (P = .011).
 

No differences in symptoms, quality of life between groups

Importantly, there were no significant differences between the discontinuation versus levothyroxine groups in terms of symptoms, and even some improvements with discontinuation, including Thyroid-Specific Quality of Life Patient-Reported Outcome (ThyPRO)-Hypothyroid Symptoms score (4.6 reduction vs. 2.2 increase), tiredness (2.6 reduction vs. 1.1 increase), and EuroQoL 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life score, for which there were no differences between groups.

There were no reports of overt hypothyroidism; hyperthyroidism; cardiovascular events including atrial fibrillation, stroke, or heart failure; osteoporotic fractures; or deaths.

One patient in the discontinuation group had a TSH level of 11 mIU/L at 6-8 weeks and switched to open-label levothyroxine 75 mcg daily. Another patient in the discontinuation group switched to open-label levothyroxine 75 mcg daily at 10 weeks due to fatigue; however, the patient was diagnosed with metastatic colon cancer 1 month later.

The finding that only about a third of patients who discontinued levothyroxine developed subclinical hypothyroidism was lower than expected, Dr. Maraka noted.

“This was ... unexpected ... for us,” she said. “We were expecting a larger number of patients to develop hypothyroidism, but to our surprise, that was not the case.”

“But what is more important is that there was no difference in the quality of life measures,” she added. “If anything, the placebo group was a little better, though the [differences] were not statistically significant.”

Dr. Maraka also noted that in further research and a final 6-month analysis, the authors will look at factors associated with developing subclinical hypothyroidism after treatment discontinuation, among other issues.
 

Discontinuation of levothyroxine is manageable

The results are encouraging, as they provide assurance that discontinuation of levothyroxine is manageable.

“This research will pave the way for initiatives to promote levothyroxine deprescription and implementation of evidence-based care for patients with subclinical hypothyroidism,” she said.

In further comments, Dr. Hennessey noted that the dilemma of having patients on levothyroxine who may not be benefitting from treatment is “significant,” with patients sometimes reluctant to discontinue treatment due to concerns of developing hypothyroidism-associated symptoms such as brain fog and weight gain.

He noted, however, that “many with mildly elevated TSH actually go on to normalize with time, so they are not really hypothyroid, [and] if we remove thyroxine from people with normal thyroid function, they will remain normal.”

Dr. Maraka has reported no relevant financial relationships. Dr. Hennessey has reported consulting for pharmaceutical companies to design clinical studies for thyroid medications.

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

MONTREAL – Patients who discontinue levothyroxine for subclinical hypothyroidism may gravitate towards becoming mildly hypothyroid again, but they importantly show no differences in terms of symptoms and quality of life – and sometimes show even improvement – compared with those who continue treatment, new research shows.

“Our results show feasibility of patient enrollment and safety of discontinuing levothyroxine in patients with subclinical hypothyroidism,” said first author Spyridoula Maraka, MD, when presenting the findings at the American Thyroid Association annual meeting.

Recommendations against levothyroxine for subclinical hypothyroidism

Subclinical hypothyroidism is commonly over-diagnosed, and treatment with thyroid hormone replacement, levothyroxine, has been shown to provide little, if any, benefit in terms of quality of life or relief of thyroid-related symptoms for these patients.

The treatment is meanwhile associated with burdens including cost and lifestyle adjustments, and one guideline panel recently issued a strong recommendation against routine levothyroxine use in most adults with subclinical hypothyroidism.

Nevertheless, levothyroxine treatment has soared in popularity and become one of the most commonly prescribed drugs in the United States.

With research lacking on one key solution of discontinuation of the therapy, Dr. Maraka, who is part of the Division of Endocrinology and Metabolism at the University of Arkansas for Medical Sciences, Little Rock, and colleagues conducted a double-blind, placebo-controlled trial at the Central Arkansas Veterans Healthcare System. In total, 50 patients treated for subclinical hypothyroidism were randomized 1:1 to continue receiving levothyroxine (25-75 mcg daily) or to discontinue treatment and receive a placebo instead, with a planned 6-month follow-up.

In the current interim analysis, Dr. Maraka reported results for the first 40 patients, including 20 randomized to levothyroxine and 20 to discontinuation.

There were no significant differences between the discontinuation and levothyroxine groups at baseline, which were of a similar age (66.2 vs. 70.8 years) and gender (75% women vs. 85% men).

The groups had similar baseline thyroid-stimulating hormone (TSH) levels (3.0 vs. 2.6 mIU/L), free T4 (both 0.9 ng/dL), thyroid peroxidase antibody positivity (17% vs. 11%), and similar clinical symptoms. All patients had at least one elevated TSH reading prior to starting levothyroxine.

With a follow-up of 6-8 weeks, 36.8% of patients in the discontinuation group had subclinical hypothyroidism, compared with 10% of patients who remained on levothyroxine (P = .0648), TSH levels were 5.5 versus 2.7 mIU/L (P = .001) and free T4 levels were 0.8 versus 0.9 ng/dL (P = .011).
 

No differences in symptoms, quality of life between groups

Importantly, there were no significant differences between the discontinuation versus levothyroxine groups in terms of symptoms, and even some improvements with discontinuation, including Thyroid-Specific Quality of Life Patient-Reported Outcome (ThyPRO)-Hypothyroid Symptoms score (4.6 reduction vs. 2.2 increase), tiredness (2.6 reduction vs. 1.1 increase), and EuroQoL 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life score, for which there were no differences between groups.

There were no reports of overt hypothyroidism; hyperthyroidism; cardiovascular events including atrial fibrillation, stroke, or heart failure; osteoporotic fractures; or deaths.

One patient in the discontinuation group had a TSH level of 11 mIU/L at 6-8 weeks and switched to open-label levothyroxine 75 mcg daily. Another patient in the discontinuation group switched to open-label levothyroxine 75 mcg daily at 10 weeks due to fatigue; however, the patient was diagnosed with metastatic colon cancer 1 month later.

The finding that only about a third of patients who discontinued levothyroxine developed subclinical hypothyroidism was lower than expected, Dr. Maraka noted.

“This was ... unexpected ... for us,” she said. “We were expecting a larger number of patients to develop hypothyroidism, but to our surprise, that was not the case.”

“But what is more important is that there was no difference in the quality of life measures,” she added. “If anything, the placebo group was a little better, though the [differences] were not statistically significant.”

Dr. Maraka also noted that in further research and a final 6-month analysis, the authors will look at factors associated with developing subclinical hypothyroidism after treatment discontinuation, among other issues.
 

Discontinuation of levothyroxine is manageable

The results are encouraging, as they provide assurance that discontinuation of levothyroxine is manageable.

“This research will pave the way for initiatives to promote levothyroxine deprescription and implementation of evidence-based care for patients with subclinical hypothyroidism,” she said.

In further comments, Dr. Hennessey noted that the dilemma of having patients on levothyroxine who may not be benefitting from treatment is “significant,” with patients sometimes reluctant to discontinue treatment due to concerns of developing hypothyroidism-associated symptoms such as brain fog and weight gain.

He noted, however, that “many with mildly elevated TSH actually go on to normalize with time, so they are not really hypothyroid, [and] if we remove thyroxine from people with normal thyroid function, they will remain normal.”

Dr. Maraka has reported no relevant financial relationships. Dr. Hennessey has reported consulting for pharmaceutical companies to design clinical studies for thyroid medications.

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

MONTREAL – Patients who discontinue levothyroxine for subclinical hypothyroidism may gravitate towards becoming mildly hypothyroid again, but they importantly show no differences in terms of symptoms and quality of life – and sometimes show even improvement – compared with those who continue treatment, new research shows.

“Our results show feasibility of patient enrollment and safety of discontinuing levothyroxine in patients with subclinical hypothyroidism,” said first author Spyridoula Maraka, MD, when presenting the findings at the American Thyroid Association annual meeting.

Recommendations against levothyroxine for subclinical hypothyroidism

Subclinical hypothyroidism is commonly over-diagnosed, and treatment with thyroid hormone replacement, levothyroxine, has been shown to provide little, if any, benefit in terms of quality of life or relief of thyroid-related symptoms for these patients.

The treatment is meanwhile associated with burdens including cost and lifestyle adjustments, and one guideline panel recently issued a strong recommendation against routine levothyroxine use in most adults with subclinical hypothyroidism.

Nevertheless, levothyroxine treatment has soared in popularity and become one of the most commonly prescribed drugs in the United States.

With research lacking on one key solution of discontinuation of the therapy, Dr. Maraka, who is part of the Division of Endocrinology and Metabolism at the University of Arkansas for Medical Sciences, Little Rock, and colleagues conducted a double-blind, placebo-controlled trial at the Central Arkansas Veterans Healthcare System. In total, 50 patients treated for subclinical hypothyroidism were randomized 1:1 to continue receiving levothyroxine (25-75 mcg daily) or to discontinue treatment and receive a placebo instead, with a planned 6-month follow-up.

In the current interim analysis, Dr. Maraka reported results for the first 40 patients, including 20 randomized to levothyroxine and 20 to discontinuation.

There were no significant differences between the discontinuation and levothyroxine groups at baseline, which were of a similar age (66.2 vs. 70.8 years) and gender (75% women vs. 85% men).

The groups had similar baseline thyroid-stimulating hormone (TSH) levels (3.0 vs. 2.6 mIU/L), free T4 (both 0.9 ng/dL), thyroid peroxidase antibody positivity (17% vs. 11%), and similar clinical symptoms. All patients had at least one elevated TSH reading prior to starting levothyroxine.

With a follow-up of 6-8 weeks, 36.8% of patients in the discontinuation group had subclinical hypothyroidism, compared with 10% of patients who remained on levothyroxine (P = .0648), TSH levels were 5.5 versus 2.7 mIU/L (P = .001) and free T4 levels were 0.8 versus 0.9 ng/dL (P = .011).
 

No differences in symptoms, quality of life between groups

Importantly, there were no significant differences between the discontinuation versus levothyroxine groups in terms of symptoms, and even some improvements with discontinuation, including Thyroid-Specific Quality of Life Patient-Reported Outcome (ThyPRO)-Hypothyroid Symptoms score (4.6 reduction vs. 2.2 increase), tiredness (2.6 reduction vs. 1.1 increase), and EuroQoL 5-Dimension Self-Report Questionnaire (EQ-5D) quality of life score, for which there were no differences between groups.

There were no reports of overt hypothyroidism; hyperthyroidism; cardiovascular events including atrial fibrillation, stroke, or heart failure; osteoporotic fractures; or deaths.

One patient in the discontinuation group had a TSH level of 11 mIU/L at 6-8 weeks and switched to open-label levothyroxine 75 mcg daily. Another patient in the discontinuation group switched to open-label levothyroxine 75 mcg daily at 10 weeks due to fatigue; however, the patient was diagnosed with metastatic colon cancer 1 month later.

The finding that only about a third of patients who discontinued levothyroxine developed subclinical hypothyroidism was lower than expected, Dr. Maraka noted.

“This was ... unexpected ... for us,” she said. “We were expecting a larger number of patients to develop hypothyroidism, but to our surprise, that was not the case.”

“But what is more important is that there was no difference in the quality of life measures,” she added. “If anything, the placebo group was a little better, though the [differences] were not statistically significant.”

Dr. Maraka also noted that in further research and a final 6-month analysis, the authors will look at factors associated with developing subclinical hypothyroidism after treatment discontinuation, among other issues.
 

Discontinuation of levothyroxine is manageable

The results are encouraging, as they provide assurance that discontinuation of levothyroxine is manageable.

“This research will pave the way for initiatives to promote levothyroxine deprescription and implementation of evidence-based care for patients with subclinical hypothyroidism,” she said.

In further comments, Dr. Hennessey noted that the dilemma of having patients on levothyroxine who may not be benefitting from treatment is “significant,” with patients sometimes reluctant to discontinue treatment due to concerns of developing hypothyroidism-associated symptoms such as brain fog and weight gain.

He noted, however, that “many with mildly elevated TSH actually go on to normalize with time, so they are not really hypothyroid, [and] if we remove thyroxine from people with normal thyroid function, they will remain normal.”

Dr. Maraka has reported no relevant financial relationships. Dr. Hennessey has reported consulting for pharmaceutical companies to design clinical studies for thyroid medications.

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

WASHINGTON – The life expectancy of non-Hispanic Black men who have sex with men (MSM) and are infected with HIV lags their White counterparts by 6.3 years under standard HIV care, new data from simulation modeling suggest.

Lead author Katherine Rich, MPH, a student at Harvard Medical School, Boston, presented the data during an annual scientific meeting on infectious diseases.

“Substantial disparities in care exist between Black and White MSM here in the United States,” she said. “The 2030 goals of the EHE [Ending the HIV Epidemic in the U.S. initiative] won’t be met until HIV-related disparities are reduced.”

Using modeling, the team was able to measure both the gaps and the potential of interventions to address those gaps.

• The team found that improving engagement in care had the largest benefit in narrowing the gap. Improving engagement and retention in care, they write, would result in a gain of 1.4 life-years for Black MSM and 1 year for White MSM.
• Annual testing would add 0.6 life-years for Black MSM and 0.3 life-years for White MSM, compared with standard care.
• In simulating viral suppression, the model-predicted gain would be 1.1 years for Black MSM and 0.3 for White.

Furthermore, a combination of annual testing, 95% engagement in care, and 95% virologic suppression would add 3.4 years for Black MSM (more than double the increase in life-years for any one intervention) and 1.6 years for their White counterparts, the research suggests.

The researchers projected life expectancy from age 15 to be 52.2 years for Black MSM (or 67.2 years old) and 58.5 years from age 15 for White MSM (or 73.5 years old), a difference of 6.3 years.

Kathleen McManus, MD, assistant professor of medicine in infectious diseases and international health at the University of Virginia, Charlottesville, said in an interview that the projected gap in years of life should be a call to action. Dr. McManus was not involved with the study.
 

Life expectancy gap ‘alarming’

“It is alarming that with current usual HIV care Black MSM with HIV have 6.3 fewer years of life expectancy than White MSM,” she said. “Black MSM having lower retention in care and a lower rate of viral suppression than White MSM demonstrates that there is a problem with our current health care delivery to Black MSM.”

With qualitative, community-engaged research, she said, “we need to ask the Black MSM community what care innovations they need – and then we need clinics and organizations to make the identified changes.”

Researchers used the validated CEPAC (Cost-Effectiveness of Preventing AIDS Complications) microsimulation HIV model to project life expectancy. Using data from the United States Centers for Disease Control and Prevention, they estimated the average age at HIV infection to be 26.8 years for Black MSM and 35 years for White MSM.

They estimated the proportion of time that MSM with diagnosed HIV are retained in care to be 75.2% for Black MSM and 80.6% for White MSM. They calculated the proportion who achieve virologic suppression to be 82% for Black MSM and 91.2% for White MSM.

Senior author Emily P. Hyle, MD, associate professor of medicine at Harvard and infectious diseases physician at Massachusetts General Hospital, both in Boston, said in a press conference before the presentation that strategies to narrow the gap will look different by region.

“Our study highlights that if you can find effective interventions, the effect can be incredibly large. These are very large differences in life-years and life expectancies,” she said.

Ms. Rich gave an example of promising interventions by pointing to work by study coauthor Aima Ahonkhai, MD, MPH, assistant professor of medicine at Vanderbilt University, Nashville, Tenn., who has received federal funding to pursue research on whether preventive care outreach in barbershops can improve prevention for Black men with HIV.

Ms. Rich noted that the modeling has limitations in that it focused on health outcomes and did not simulate transmissions. Results also reflect national data and not local HIV care continuums, which, she acknowledged, differ substantially.

Dr. McManus and the study authors have reported no relevant financial relationships.

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

WASHINGTON – The life expectancy of non-Hispanic Black men who have sex with men (MSM) and are infected with HIV lags their White counterparts by 6.3 years under standard HIV care, new data from simulation modeling suggest.

Lead author Katherine Rich, MPH, a student at Harvard Medical School, Boston, presented the data during an annual scientific meeting on infectious diseases.

“Substantial disparities in care exist between Black and White MSM here in the United States,” she said. “The 2030 goals of the EHE [Ending the HIV Epidemic in the U.S. initiative] won’t be met until HIV-related disparities are reduced.”

Using modeling, the team was able to measure both the gaps and the potential of interventions to address those gaps.

• The team found that improving engagement in care had the largest benefit in narrowing the gap. Improving engagement and retention in care, they write, would result in a gain of 1.4 life-years for Black MSM and 1 year for White MSM.
• Annual testing would add 0.6 life-years for Black MSM and 0.3 life-years for White MSM, compared with standard care.
• In simulating viral suppression, the model-predicted gain would be 1.1 years for Black MSM and 0.3 for White.

Furthermore, a combination of annual testing, 95% engagement in care, and 95% virologic suppression would add 3.4 years for Black MSM (more than double the increase in life-years for any one intervention) and 1.6 years for their White counterparts, the research suggests.

The researchers projected life expectancy from age 15 to be 52.2 years for Black MSM (or 67.2 years old) and 58.5 years from age 15 for White MSM (or 73.5 years old), a difference of 6.3 years.

Kathleen McManus, MD, assistant professor of medicine in infectious diseases and international health at the University of Virginia, Charlottesville, said in an interview that the projected gap in years of life should be a call to action. Dr. McManus was not involved with the study.
 

Life expectancy gap ‘alarming’

“It is alarming that with current usual HIV care Black MSM with HIV have 6.3 fewer years of life expectancy than White MSM,” she said. “Black MSM having lower retention in care and a lower rate of viral suppression than White MSM demonstrates that there is a problem with our current health care delivery to Black MSM.”

With qualitative, community-engaged research, she said, “we need to ask the Black MSM community what care innovations they need – and then we need clinics and organizations to make the identified changes.”

Researchers used the validated CEPAC (Cost-Effectiveness of Preventing AIDS Complications) microsimulation HIV model to project life expectancy. Using data from the United States Centers for Disease Control and Prevention, they estimated the average age at HIV infection to be 26.8 years for Black MSM and 35 years for White MSM.

They estimated the proportion of time that MSM with diagnosed HIV are retained in care to be 75.2% for Black MSM and 80.6% for White MSM. They calculated the proportion who achieve virologic suppression to be 82% for Black MSM and 91.2% for White MSM.

Senior author Emily P. Hyle, MD, associate professor of medicine at Harvard and infectious diseases physician at Massachusetts General Hospital, both in Boston, said in a press conference before the presentation that strategies to narrow the gap will look different by region.

“Our study highlights that if you can find effective interventions, the effect can be incredibly large. These are very large differences in life-years and life expectancies,” she said.

Ms. Rich gave an example of promising interventions by pointing to work by study coauthor Aima Ahonkhai, MD, MPH, assistant professor of medicine at Vanderbilt University, Nashville, Tenn., who has received federal funding to pursue research on whether preventive care outreach in barbershops can improve prevention for Black men with HIV.

Ms. Rich noted that the modeling has limitations in that it focused on health outcomes and did not simulate transmissions. Results also reflect national data and not local HIV care continuums, which, she acknowledged, differ substantially.

Dr. McManus and the study authors have reported no relevant financial relationships.

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

WASHINGTON – The life expectancy of non-Hispanic Black men who have sex with men (MSM) and are infected with HIV lags their White counterparts by 6.3 years under standard HIV care, new data from simulation modeling suggest.

Lead author Katherine Rich, MPH, a student at Harvard Medical School, Boston, presented the data during an annual scientific meeting on infectious diseases.

“Substantial disparities in care exist between Black and White MSM here in the United States,” she said. “The 2030 goals of the EHE [Ending the HIV Epidemic in the U.S. initiative] won’t be met until HIV-related disparities are reduced.”

Using modeling, the team was able to measure both the gaps and the potential of interventions to address those gaps.

• The team found that improving engagement in care had the largest benefit in narrowing the gap. Improving engagement and retention in care, they write, would result in a gain of 1.4 life-years for Black MSM and 1 year for White MSM.
• Annual testing would add 0.6 life-years for Black MSM and 0.3 life-years for White MSM, compared with standard care.
• In simulating viral suppression, the model-predicted gain would be 1.1 years for Black MSM and 0.3 for White.

Furthermore, a combination of annual testing, 95% engagement in care, and 95% virologic suppression would add 3.4 years for Black MSM (more than double the increase in life-years for any one intervention) and 1.6 years for their White counterparts, the research suggests.

The researchers projected life expectancy from age 15 to be 52.2 years for Black MSM (or 67.2 years old) and 58.5 years from age 15 for White MSM (or 73.5 years old), a difference of 6.3 years.

Kathleen McManus, MD, assistant professor of medicine in infectious diseases and international health at the University of Virginia, Charlottesville, said in an interview that the projected gap in years of life should be a call to action. Dr. McManus was not involved with the study.
 

Life expectancy gap ‘alarming’

“It is alarming that with current usual HIV care Black MSM with HIV have 6.3 fewer years of life expectancy than White MSM,” she said. “Black MSM having lower retention in care and a lower rate of viral suppression than White MSM demonstrates that there is a problem with our current health care delivery to Black MSM.”

With qualitative, community-engaged research, she said, “we need to ask the Black MSM community what care innovations they need – and then we need clinics and organizations to make the identified changes.”

Researchers used the validated CEPAC (Cost-Effectiveness of Preventing AIDS Complications) microsimulation HIV model to project life expectancy. Using data from the United States Centers for Disease Control and Prevention, they estimated the average age at HIV infection to be 26.8 years for Black MSM and 35 years for White MSM.

They estimated the proportion of time that MSM with diagnosed HIV are retained in care to be 75.2% for Black MSM and 80.6% for White MSM. They calculated the proportion who achieve virologic suppression to be 82% for Black MSM and 91.2% for White MSM.

Senior author Emily P. Hyle, MD, associate professor of medicine at Harvard and infectious diseases physician at Massachusetts General Hospital, both in Boston, said in a press conference before the presentation that strategies to narrow the gap will look different by region.

“Our study highlights that if you can find effective interventions, the effect can be incredibly large. These are very large differences in life-years and life expectancies,” she said.

Ms. Rich gave an example of promising interventions by pointing to work by study coauthor Aima Ahonkhai, MD, MPH, assistant professor of medicine at Vanderbilt University, Nashville, Tenn., who has received federal funding to pursue research on whether preventive care outreach in barbershops can improve prevention for Black men with HIV.

Ms. Rich noted that the modeling has limitations in that it focused on health outcomes and did not simulate transmissions. Results also reflect national data and not local HIV care continuums, which, she acknowledged, differ substantially.

Dr. McManus and the study authors have reported no relevant financial relationships.

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

What you really don’t want to do, if you want to improve diversity, equity, and inclusion (DEI) at your academic institution, is to recruit diverse people to your program and then have them come and feel not included, said Vivian Asare, MD. “That can work against your efforts,” she stated in an oral presentation at the annual meeting of the American College of Chest Physicians (CHEST). Dr. Asare is assistant professor and vice chief of DEI for Yale Pulmonary, Critical Care, and Sleep Medicine, and associate medical director of Yale Centers for Sleep Medicine, New Haven, Conn.

In offering a path to successful DEI, Dr. Asare said: “The first step is to build a team and discuss your mission. Invite everyone to participate and include your leadership because they’re the ones who set the stage, ensure sustainability, and can be a liaison with faculty.” Then a DEI leader should be elected, she added.

The next and very important step is to survey the current institutional climate. “You need to tap into how people feel about DEI in your program.” That entails speaking directly with the stakeholders (faculty, staff, trainees) and identifying their specific concerns and what they think is lacking. Retreats, serious group discussions, and self-reflecting (asking “what initiatives would be good for us?”), and meeting one-on-one with individuals for a truly personalized approach are among potentially productive strategies for identifying the priorities and DEI-related topics specific to a particular academic sleep program.

Dr. Asare offered up a sample DEI survey (Am J Obstet Gynecol. 2020 Nov;223[5]:715.e1-715.e7), that made direct statements inviting the respondent to check off one of the following responses: Yes, No, Somewhat, Do not know, and Not applicable. Among sample statements:

• Our department is actively committed to issues of diversity, equity, and inclusion.
• Faculty searches in the department regularly attract a diverse pool of highly qualified candidates and/or attract a pool that represents the availability of MDs in this field.
• Our outreach and recruitment processes employ targeted practices for attracting diverse populations.

Dr. Asare said that a survey can be a simple approach for garnering information that can be useful for prioritizing DEI topics of concern and igniting interest in them. Engagement requires regular DEI committee meetings with minutes or a newsletter and with updates and topics brought to faculty meetings.
 

Key DEI areas of focus

Dr. Asare listed several key DEI areas: Recruitment/retention, mentorship, scholarship, and inclusion and community engagement. Under scholarship, for example, she cited topics for potential inclusion in a DEI curriculum: Unconscious bias and anti-racism training, racism, discrimination and microaggression education (bystander/deescalation training), cultural competency and awareness, workplace civility, and health disparities. “We all know that implicit bias in providers is a reality, unfortunately,” Dr. Asare said. Being aware of these implicit biases is a start, but instruction on how to actively overcome them has to be provided. Tools may include perspective-taking, exploring common identity, and self-reflection.

To create an inclusive environment for all faculty, trainees, and staff may involve establishing a “welcome committee” for new faculty, perhaps with designating a “peer buddy,” creating social events and other opportunities for all opinions and ideas to be heard and valued. Particularly for underserved and disadvantaged patient populations, patient advocacy and community service need to be fostered through support groups and provision of resources.

Summarizing, Dr. Asare reiterated several key elements for a successful DEI program: Build a team and discuss the mission, survey the current climate allowing open communication and dialogue, plan and engage, organize, and form areas of DEI focus. Find out where you are and where you want to be with respect to DEI, she concluded.

Dr. Asare declared that she had no conflicts of interest.

What you really don’t want to do, if you want to improve diversity, equity, and inclusion (DEI) at your academic institution, is to recruit diverse people to your program and then have them come and feel not included, said Vivian Asare, MD. “That can work against your efforts,” she stated in an oral presentation at the annual meeting of the American College of Chest Physicians (CHEST). Dr. Asare is assistant professor and vice chief of DEI for Yale Pulmonary, Critical Care, and Sleep Medicine, and associate medical director of Yale Centers for Sleep Medicine, New Haven, Conn.

In offering a path to successful DEI, Dr. Asare said: “The first step is to build a team and discuss your mission. Invite everyone to participate and include your leadership because they’re the ones who set the stage, ensure sustainability, and can be a liaison with faculty.” Then a DEI leader should be elected, she added.

The next and very important step is to survey the current institutional climate. “You need to tap into how people feel about DEI in your program.” That entails speaking directly with the stakeholders (faculty, staff, trainees) and identifying their specific concerns and what they think is lacking. Retreats, serious group discussions, and self-reflecting (asking “what initiatives would be good for us?”), and meeting one-on-one with individuals for a truly personalized approach are among potentially productive strategies for identifying the priorities and DEI-related topics specific to a particular academic sleep program.

Dr. Asare offered up a sample DEI survey (Am J Obstet Gynecol. 2020 Nov;223[5]:715.e1-715.e7), that made direct statements inviting the respondent to check off one of the following responses: Yes, No, Somewhat, Do not know, and Not applicable. Among sample statements:

• Our department is actively committed to issues of diversity, equity, and inclusion.
• Faculty searches in the department regularly attract a diverse pool of highly qualified candidates and/or attract a pool that represents the availability of MDs in this field.
• Our outreach and recruitment processes employ targeted practices for attracting diverse populations.

Dr. Asare said that a survey can be a simple approach for garnering information that can be useful for prioritizing DEI topics of concern and igniting interest in them. Engagement requires regular DEI committee meetings with minutes or a newsletter and with updates and topics brought to faculty meetings.
 

Key DEI areas of focus

Dr. Asare listed several key DEI areas: Recruitment/retention, mentorship, scholarship, and inclusion and community engagement. Under scholarship, for example, she cited topics for potential inclusion in a DEI curriculum: Unconscious bias and anti-racism training, racism, discrimination and microaggression education (bystander/deescalation training), cultural competency and awareness, workplace civility, and health disparities. “We all know that implicit bias in providers is a reality, unfortunately,” Dr. Asare said. Being aware of these implicit biases is a start, but instruction on how to actively overcome them has to be provided. Tools may include perspective-taking, exploring common identity, and self-reflection.

To create an inclusive environment for all faculty, trainees, and staff may involve establishing a “welcome committee” for new faculty, perhaps with designating a “peer buddy,” creating social events and other opportunities for all opinions and ideas to be heard and valued. Particularly for underserved and disadvantaged patient populations, patient advocacy and community service need to be fostered through support groups and provision of resources.

Summarizing, Dr. Asare reiterated several key elements for a successful DEI program: Build a team and discuss the mission, survey the current climate allowing open communication and dialogue, plan and engage, organize, and form areas of DEI focus. Find out where you are and where you want to be with respect to DEI, she concluded.

Dr. Asare declared that she had no conflicts of interest.

What you really don’t want to do, if you want to improve diversity, equity, and inclusion (DEI) at your academic institution, is to recruit diverse people to your program and then have them come and feel not included, said Vivian Asare, MD. “That can work against your efforts,” she stated in an oral presentation at the annual meeting of the American College of Chest Physicians (CHEST). Dr. Asare is assistant professor and vice chief of DEI for Yale Pulmonary, Critical Care, and Sleep Medicine, and associate medical director of Yale Centers for Sleep Medicine, New Haven, Conn.

In offering a path to successful DEI, Dr. Asare said: “The first step is to build a team and discuss your mission. Invite everyone to participate and include your leadership because they’re the ones who set the stage, ensure sustainability, and can be a liaison with faculty.” Then a DEI leader should be elected, she added.

The next and very important step is to survey the current institutional climate. “You need to tap into how people feel about DEI in your program.” That entails speaking directly with the stakeholders (faculty, staff, trainees) and identifying their specific concerns and what they think is lacking. Retreats, serious group discussions, and self-reflecting (asking “what initiatives would be good for us?”), and meeting one-on-one with individuals for a truly personalized approach are among potentially productive strategies for identifying the priorities and DEI-related topics specific to a particular academic sleep program.

Dr. Asare offered up a sample DEI survey (Am J Obstet Gynecol. 2020 Nov;223[5]:715.e1-715.e7), that made direct statements inviting the respondent to check off one of the following responses: Yes, No, Somewhat, Do not know, and Not applicable. Among sample statements:

• Our department is actively committed to issues of diversity, equity, and inclusion.
• Faculty searches in the department regularly attract a diverse pool of highly qualified candidates and/or attract a pool that represents the availability of MDs in this field.
• Our outreach and recruitment processes employ targeted practices for attracting diverse populations.

Dr. Asare said that a survey can be a simple approach for garnering information that can be useful for prioritizing DEI topics of concern and igniting interest in them. Engagement requires regular DEI committee meetings with minutes or a newsletter and with updates and topics brought to faculty meetings.
 

Key DEI areas of focus

Dr. Asare listed several key DEI areas: Recruitment/retention, mentorship, scholarship, and inclusion and community engagement. Under scholarship, for example, she cited topics for potential inclusion in a DEI curriculum: Unconscious bias and anti-racism training, racism, discrimination and microaggression education (bystander/deescalation training), cultural competency and awareness, workplace civility, and health disparities. “We all know that implicit bias in providers is a reality, unfortunately,” Dr. Asare said. Being aware of these implicit biases is a start, but instruction on how to actively overcome them has to be provided. Tools may include perspective-taking, exploring common identity, and self-reflection.

To create an inclusive environment for all faculty, trainees, and staff may involve establishing a “welcome committee” for new faculty, perhaps with designating a “peer buddy,” creating social events and other opportunities for all opinions and ideas to be heard and valued. Particularly for underserved and disadvantaged patient populations, patient advocacy and community service need to be fostered through support groups and provision of resources.

Summarizing, Dr. Asare reiterated several key elements for a successful DEI program: Build a team and discuss the mission, survey the current climate allowing open communication and dialogue, plan and engage, organize, and form areas of DEI focus. Find out where you are and where you want to be with respect to DEI, she concluded.

Dr. Asare declared that she had no conflicts of interest.

Sarah Sheffield, a nurse practitioner at a Veterans Affairs clinic in Eugene, Oregon, had a problem. Her patients — mostly in their 70s and beyond — couldn’t read computer screens. It’s not an unusual problem for older people, which is why you might think Oracle Cerner, the developers of the agency’s new digital health record system, would have anticipated it.

But they didn’t.

Federal law requires government resources to be accessible to patients with disabilities. But patients can’t easily enlarge the text. “They all learned to get strong reading glasses and magnifying glasses,” said Sheffield, who retired in early October.

The difficulties are everyday reminders of a dire reality for patients in the VA system. More than a million patients are blind or have low vision. They rely on software to access prescriptions or send messages to their doctors. But often the technology fails them. Either the screens don’t allow users to zoom in on the text, or screen-reader software that translates text to speech isn’t compatible.

“None of the systems are accessible” to these patients, said Donald Overton, executive director of the Blinded Veterans Association.

Patients often struggle even to log into websites or enter basic information needed to check in for hospital visits, Overton said: “We find our community stops trying, checks out, and disengages. They become dependent on other individuals; they give up independence.”

Now, the developing VA medical record system, already bloated by outsize costs, has been delayed until June 2023. So far, the project has threatened to exacerbate those issues.

While users in general have been affected by numerous incidents of downtime, delayed care, and missing information, barriers to access are particularly acute for blind and low-vision users — whether patients or workers within the health system. At least one Oregon-based employee has been offered aid — a helper assigned to read and click buttons — to navigate the system.

Over 1,000 Section 508 complaints are in a backlog to be assessed, or assigned to Oracle Cerner to fix, Veterans Affairs spokesperson Terrence Hayes confirmed. That section is part of federal law guaranteeing people with disabilities access to government technology.

Hayes said the problems described by these complaints don’t prevent employees and patients with disabilities from using the system. The complaints — 469 of which have been assigned to Oracle Cerner to fix, he said — mean that users’ disabilities make it more difficult, to the point of requiring mitigation.

The project is under new management with big promises. North Kansas City, Missouri-based developer Cerner, which originally landed the VA contract, was recently taken over by database technology giant Oracle, which plans to overhaul the software, company executive Mike Sicilia said during a September Senate hearing. “We intend to rewrite” the system, he said. “We have found nothing that can’t be addressed in relatively short order.”

But that will happen under continued scrutiny. Rep. Mark Takano (D-Calif.), chair of the House Veterans Affairs Committee, said his panel would continue to oversee the department’s compliance with accessibility standards. “Whether they work for VA or receive health care and benefits, the needs of veterans must be addressed by companies that want to work with the VA,” he said.

Takano, along with fellow Democrats Sens. Bob Casey of Pennsylvania and Jon Tester of Montana, sent a letter Oct. 7 to VA Secretary Denis McDonough noting the significant gaps in the agency’s systems, and urging VA to engage with all disabled veterans, not merely those who are blind.

VA was alerted early and often that Cerner’s software posed problems for blind- and low-vision users, interviews and a review of records show. As early as 2015, when the Department of Defense and VA were exploring purchasing new systems, the National Federation of the Blind submitted letters to both departments, and Cerner, expressing concerns that the product would be unusable for clinicians and patients.

Alerts also came from inside VA. “We pointed out to Cerner that their system was really dependent on vision and that it was a major problem. The icons are really, really small,” said Dr. Art Wallace, a VA anesthesiologist who participated in one of the agency’s user groups to provide input for the eventual design of the system.

The Cerner system, he told the agency and KHN, is user-unfriendly. On the clinician side, it requires multiple high-resolution monitors to display a patient’s entire record, and VA facilities don’t always enjoy that wealth of equipment. “It would be very hard for visually impaired people, or normal people wearing bifocals, to use,” he concluded.

Before the software was rolled out, the system also failed a test with an employee working with a team at Oregon’s White City VA Medical Center devoted to helping blind patients develop skills and independence, said Carolyn Schwab, president of the American Federation of Government Employees Local 1042.

In the testing, the system didn’t work with adaptive equipment, like text-to-speech software, she said. Despite receiving these complaints about the system, VA and Cerner “implemented it anyway.” Recently, when a regional AFGE president asked VA why they used the software — despite the federal mandates — he received no response, Schwab said.

Some within the company also thought there would be struggles. Two former Cerner employees said the standard medical record system was getting long in the tooth when VA signed an agreement to purchase and customize the product.

Because it was built on old code, the software was difficult to patch when problems were discovered, the employees said. What’s more, according to the employees, Cerner took a doggedly incremental approach to fixing errors. If someone complained about a malfunctioning button on a page filled with other potholes, the company would fix just that button — not the whole page, the employees said.

VA spokesperson Hayes denied the claims, saying the developer and department try to address problems holistically. Cerner did not respond to multiple requests for comment.

Accessibility errors are as present in private sector medical record systems as public. Cerner patched up a bug with the Safari web browser’s rendering of its patient portal when the Massachusetts Institute of Technology’s student clinic threatened legal action, the former employees said. (“MIT Medical does not, as a general practice, discuss individual vendor contracts or services,” said spokesperson David Tytell.)

Legal threats — with hospital systems and medical record systems routinely facing lawsuits — are the most obvious symptom of a lack of accessibility within the U.S. health care system.

Deep inaccessibility plagues the burgeoning telehealth sector. A recent survey from the American Federation for the Blind found that 57% of respondents struggled to use providers’ proprietary telehealth platforms. Some resorted to FaceTime. Many said they were unable to log in or couldn’t read information transmitted through chat sidebars.

Existing federal regulations could, in theory, be used to enforce higher standards of accessibility in health technology. The Department of Health and Human Services Office for Civil Rights issued guidance during the pandemic on making telehealth technologies easier to use for patients with disabilities. And other agencies could start leaning on hospitals, because they are recipients of government dollars or federal vendors, to make sure their offerings work for such patients.

That might not happen. These regulations could prove toothless, advocates warn. While there are several laws on the books, the advocates argue that enforcement and tougher regulations have not been forthcoming. “The concern from stakeholders is: Are you going to slow-walk this again?” said Joe Nahra, director of government relations at Powers Law, a Washington, D.C., law firm.

Building in accessibility has historically benefited all users. Voice assistance technology was originally developed to help blind- and low-vision users before winning widespread popularity with gadgets like Siri and Alexa.

Disability advocates believe vendors often push technology ahead without properly considering the impact on the people who will rely on it. “In the rush to be the first one, they put accessibility on the back burner,” said Eve Hill, a disability rights attorney with Brown, Goldstein & Levy, a civil rights law firm.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Sarah Sheffield, a nurse practitioner at a Veterans Affairs clinic in Eugene, Oregon, had a problem. Her patients — mostly in their 70s and beyond — couldn’t read computer screens. It’s not an unusual problem for older people, which is why you might think Oracle Cerner, the developers of the agency’s new digital health record system, would have anticipated it.

But they didn’t.

Federal law requires government resources to be accessible to patients with disabilities. But patients can’t easily enlarge the text. “They all learned to get strong reading glasses and magnifying glasses,” said Sheffield, who retired in early October.

The difficulties are everyday reminders of a dire reality for patients in the VA system. More than a million patients are blind or have low vision. They rely on software to access prescriptions or send messages to their doctors. But often the technology fails them. Either the screens don’t allow users to zoom in on the text, or screen-reader software that translates text to speech isn’t compatible.

“None of the systems are accessible” to these patients, said Donald Overton, executive director of the Blinded Veterans Association.

Patients often struggle even to log into websites or enter basic information needed to check in for hospital visits, Overton said: “We find our community stops trying, checks out, and disengages. They become dependent on other individuals; they give up independence.”

Now, the developing VA medical record system, already bloated by outsize costs, has been delayed until June 2023. So far, the project has threatened to exacerbate those issues.

While users in general have been affected by numerous incidents of downtime, delayed care, and missing information, barriers to access are particularly acute for blind and low-vision users — whether patients or workers within the health system. At least one Oregon-based employee has been offered aid — a helper assigned to read and click buttons — to navigate the system.

Over 1,000 Section 508 complaints are in a backlog to be assessed, or assigned to Oracle Cerner to fix, Veterans Affairs spokesperson Terrence Hayes confirmed. That section is part of federal law guaranteeing people with disabilities access to government technology.

Hayes said the problems described by these complaints don’t prevent employees and patients with disabilities from using the system. The complaints — 469 of which have been assigned to Oracle Cerner to fix, he said — mean that users’ disabilities make it more difficult, to the point of requiring mitigation.

The project is under new management with big promises. North Kansas City, Missouri-based developer Cerner, which originally landed the VA contract, was recently taken over by database technology giant Oracle, which plans to overhaul the software, company executive Mike Sicilia said during a September Senate hearing. “We intend to rewrite” the system, he said. “We have found nothing that can’t be addressed in relatively short order.”

But that will happen under continued scrutiny. Rep. Mark Takano (D-Calif.), chair of the House Veterans Affairs Committee, said his panel would continue to oversee the department’s compliance with accessibility standards. “Whether they work for VA or receive health care and benefits, the needs of veterans must be addressed by companies that want to work with the VA,” he said.

Takano, along with fellow Democrats Sens. Bob Casey of Pennsylvania and Jon Tester of Montana, sent a letter Oct. 7 to VA Secretary Denis McDonough noting the significant gaps in the agency’s systems, and urging VA to engage with all disabled veterans, not merely those who are blind.

VA was alerted early and often that Cerner’s software posed problems for blind- and low-vision users, interviews and a review of records show. As early as 2015, when the Department of Defense and VA were exploring purchasing new systems, the National Federation of the Blind submitted letters to both departments, and Cerner, expressing concerns that the product would be unusable for clinicians and patients.

Alerts also came from inside VA. “We pointed out to Cerner that their system was really dependent on vision and that it was a major problem. The icons are really, really small,” said Dr. Art Wallace, a VA anesthesiologist who participated in one of the agency’s user groups to provide input for the eventual design of the system.

The Cerner system, he told the agency and KHN, is user-unfriendly. On the clinician side, it requires multiple high-resolution monitors to display a patient’s entire record, and VA facilities don’t always enjoy that wealth of equipment. “It would be very hard for visually impaired people, or normal people wearing bifocals, to use,” he concluded.

Before the software was rolled out, the system also failed a test with an employee working with a team at Oregon’s White City VA Medical Center devoted to helping blind patients develop skills and independence, said Carolyn Schwab, president of the American Federation of Government Employees Local 1042.

In the testing, the system didn’t work with adaptive equipment, like text-to-speech software, she said. Despite receiving these complaints about the system, VA and Cerner “implemented it anyway.” Recently, when a regional AFGE president asked VA why they used the software — despite the federal mandates — he received no response, Schwab said.

Some within the company also thought there would be struggles. Two former Cerner employees said the standard medical record system was getting long in the tooth when VA signed an agreement to purchase and customize the product.

Because it was built on old code, the software was difficult to patch when problems were discovered, the employees said. What’s more, according to the employees, Cerner took a doggedly incremental approach to fixing errors. If someone complained about a malfunctioning button on a page filled with other potholes, the company would fix just that button — not the whole page, the employees said.

VA spokesperson Hayes denied the claims, saying the developer and department try to address problems holistically. Cerner did not respond to multiple requests for comment.

Accessibility errors are as present in private sector medical record systems as public. Cerner patched up a bug with the Safari web browser’s rendering of its patient portal when the Massachusetts Institute of Technology’s student clinic threatened legal action, the former employees said. (“MIT Medical does not, as a general practice, discuss individual vendor contracts or services,” said spokesperson David Tytell.)

Legal threats — with hospital systems and medical record systems routinely facing lawsuits — are the most obvious symptom of a lack of accessibility within the U.S. health care system.

Deep inaccessibility plagues the burgeoning telehealth sector. A recent survey from the American Federation for the Blind found that 57% of respondents struggled to use providers’ proprietary telehealth platforms. Some resorted to FaceTime. Many said they were unable to log in or couldn’t read information transmitted through chat sidebars.

Existing federal regulations could, in theory, be used to enforce higher standards of accessibility in health technology. The Department of Health and Human Services Office for Civil Rights issued guidance during the pandemic on making telehealth technologies easier to use for patients with disabilities. And other agencies could start leaning on hospitals, because they are recipients of government dollars or federal vendors, to make sure their offerings work for such patients.

That might not happen. These regulations could prove toothless, advocates warn. While there are several laws on the books, the advocates argue that enforcement and tougher regulations have not been forthcoming. “The concern from stakeholders is: Are you going to slow-walk this again?” said Joe Nahra, director of government relations at Powers Law, a Washington, D.C., law firm.

Building in accessibility has historically benefited all users. Voice assistance technology was originally developed to help blind- and low-vision users before winning widespread popularity with gadgets like Siri and Alexa.

Disability advocates believe vendors often push technology ahead without properly considering the impact on the people who will rely on it. “In the rush to be the first one, they put accessibility on the back burner,” said Eve Hill, a disability rights attorney with Brown, Goldstein & Levy, a civil rights law firm.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Sarah Sheffield, a nurse practitioner at a Veterans Affairs clinic in Eugene, Oregon, had a problem. Her patients — mostly in their 70s and beyond — couldn’t read computer screens. It’s not an unusual problem for older people, which is why you might think Oracle Cerner, the developers of the agency’s new digital health record system, would have anticipated it.

But they didn’t.

Federal law requires government resources to be accessible to patients with disabilities. But patients can’t easily enlarge the text. “They all learned to get strong reading glasses and magnifying glasses,” said Sheffield, who retired in early October.

The difficulties are everyday reminders of a dire reality for patients in the VA system. More than a million patients are blind or have low vision. They rely on software to access prescriptions or send messages to their doctors. But often the technology fails them. Either the screens don’t allow users to zoom in on the text, or screen-reader software that translates text to speech isn’t compatible.

“None of the systems are accessible” to these patients, said Donald Overton, executive director of the Blinded Veterans Association.

Patients often struggle even to log into websites or enter basic information needed to check in for hospital visits, Overton said: “We find our community stops trying, checks out, and disengages. They become dependent on other individuals; they give up independence.”

Now, the developing VA medical record system, already bloated by outsize costs, has been delayed until June 2023. So far, the project has threatened to exacerbate those issues.

While users in general have been affected by numerous incidents of downtime, delayed care, and missing information, barriers to access are particularly acute for blind and low-vision users — whether patients or workers within the health system. At least one Oregon-based employee has been offered aid — a helper assigned to read and click buttons — to navigate the system.

Over 1,000 Section 508 complaints are in a backlog to be assessed, or assigned to Oracle Cerner to fix, Veterans Affairs spokesperson Terrence Hayes confirmed. That section is part of federal law guaranteeing people with disabilities access to government technology.

Hayes said the problems described by these complaints don’t prevent employees and patients with disabilities from using the system. The complaints — 469 of which have been assigned to Oracle Cerner to fix, he said — mean that users’ disabilities make it more difficult, to the point of requiring mitigation.

The project is under new management with big promises. North Kansas City, Missouri-based developer Cerner, which originally landed the VA contract, was recently taken over by database technology giant Oracle, which plans to overhaul the software, company executive Mike Sicilia said during a September Senate hearing. “We intend to rewrite” the system, he said. “We have found nothing that can’t be addressed in relatively short order.”

But that will happen under continued scrutiny. Rep. Mark Takano (D-Calif.), chair of the House Veterans Affairs Committee, said his panel would continue to oversee the department’s compliance with accessibility standards. “Whether they work for VA or receive health care and benefits, the needs of veterans must be addressed by companies that want to work with the VA,” he said.

Takano, along with fellow Democrats Sens. Bob Casey of Pennsylvania and Jon Tester of Montana, sent a letter Oct. 7 to VA Secretary Denis McDonough noting the significant gaps in the agency’s systems, and urging VA to engage with all disabled veterans, not merely those who are blind.

VA was alerted early and often that Cerner’s software posed problems for blind- and low-vision users, interviews and a review of records show. As early as 2015, when the Department of Defense and VA were exploring purchasing new systems, the National Federation of the Blind submitted letters to both departments, and Cerner, expressing concerns that the product would be unusable for clinicians and patients.

Alerts also came from inside VA. “We pointed out to Cerner that their system was really dependent on vision and that it was a major problem. The icons are really, really small,” said Dr. Art Wallace, a VA anesthesiologist who participated in one of the agency’s user groups to provide input for the eventual design of the system.

The Cerner system, he told the agency and KHN, is user-unfriendly. On the clinician side, it requires multiple high-resolution monitors to display a patient’s entire record, and VA facilities don’t always enjoy that wealth of equipment. “It would be very hard for visually impaired people, or normal people wearing bifocals, to use,” he concluded.

Before the software was rolled out, the system also failed a test with an employee working with a team at Oregon’s White City VA Medical Center devoted to helping blind patients develop skills and independence, said Carolyn Schwab, president of the American Federation of Government Employees Local 1042.

In the testing, the system didn’t work with adaptive equipment, like text-to-speech software, she said. Despite receiving these complaints about the system, VA and Cerner “implemented it anyway.” Recently, when a regional AFGE president asked VA why they used the software — despite the federal mandates — he received no response, Schwab said.

Some within the company also thought there would be struggles. Two former Cerner employees said the standard medical record system was getting long in the tooth when VA signed an agreement to purchase and customize the product.

Because it was built on old code, the software was difficult to patch when problems were discovered, the employees said. What’s more, according to the employees, Cerner took a doggedly incremental approach to fixing errors. If someone complained about a malfunctioning button on a page filled with other potholes, the company would fix just that button — not the whole page, the employees said.

VA spokesperson Hayes denied the claims, saying the developer and department try to address problems holistically. Cerner did not respond to multiple requests for comment.

Accessibility errors are as present in private sector medical record systems as public. Cerner patched up a bug with the Safari web browser’s rendering of its patient portal when the Massachusetts Institute of Technology’s student clinic threatened legal action, the former employees said. (“MIT Medical does not, as a general practice, discuss individual vendor contracts or services,” said spokesperson David Tytell.)

Legal threats — with hospital systems and medical record systems routinely facing lawsuits — are the most obvious symptom of a lack of accessibility within the U.S. health care system.

Deep inaccessibility plagues the burgeoning telehealth sector. A recent survey from the American Federation for the Blind found that 57% of respondents struggled to use providers’ proprietary telehealth platforms. Some resorted to FaceTime. Many said they were unable to log in or couldn’t read information transmitted through chat sidebars.

Existing federal regulations could, in theory, be used to enforce higher standards of accessibility in health technology. The Department of Health and Human Services Office for Civil Rights issued guidance during the pandemic on making telehealth technologies easier to use for patients with disabilities. And other agencies could start leaning on hospitals, because they are recipients of government dollars or federal vendors, to make sure their offerings work for such patients.

That might not happen. These regulations could prove toothless, advocates warn. While there are several laws on the books, the advocates argue that enforcement and tougher regulations have not been forthcoming. “The concern from stakeholders is: Are you going to slow-walk this again?” said Joe Nahra, director of government relations at Powers Law, a Washington, D.C., law firm.

Building in accessibility has historically benefited all users. Voice assistance technology was originally developed to help blind- and low-vision users before winning widespread popularity with gadgets like Siri and Alexa.

Disability advocates believe vendors often push technology ahead without properly considering the impact on the people who will rely on it. “In the rush to be the first one, they put accessibility on the back burner,” said Eve Hill, a disability rights attorney with Brown, Goldstein & Levy, a civil rights law firm.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The Food and Drug Administration has approved a new immunotherapy combination for use in the treatment of unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer.

The new combination comprises a single dose of tremelimumab (Imjudo, AstraZeneca) followed by treatment with durvalumab (Imfinzi, AstraZeneca) in what is known as the STRIDE (single-tremelimumab regular-interval durvalumab) regimen.

This marks the first worldwide approval for tremelimumab, which is a CTLA-4 antibody.

The other drug in the combination, durvalumab, is an anti-PDL1 antibody and is already approved by the FDA for use in several tumor types, including lung cancer, bladder cancer, and biliary tract cancers.

The STRIDE regimen is composed of a single 300-mg dose of tremelimumab followed by durvalumab 1,500 mg given every 4 weeks.

This regimen was used in the HIMALAYA phase 3 trial, which was published in June 2022 in the New England Journal of Medicine.

Results from this trial showed that 30% of patients treated with that combination were still alive at 3 years, compared with 20% of patients who were treated with the standard regimen, sorafenib.

“In addition to this regimen demonstrating a favorable 3-year survival rate in the HIMALAYA trial, safety data showed no increase in severe liver toxicity or bleeding risk for the combination, important factors for patients with liver cancer who also have advanced liver disease,” commented the principal investigator of this trial, Ghassan Abou-Alfa, MD, MBA, attending physician at Memorial Sloan Kettering Cancer Center, New York.

“Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival,” he commented in a press release from the drug’s manufacturer, AstraZeneca.

When the results from this trial were presented earlier this year at the ASCO Gastrointestinal Cancers meeting, the discussant for that abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, suggested that the STRIDE regimen offers a new first-line treatment option for patients with advanced HCC.

He also made several comments about the design of the HIMALAYA trial, which has a third treatment arm in which patients received durvalumab alone. Dr. El-Khoueiry noted that single-agent durvalumab was noninferior to sorafenib, but he added that no conclusions could be drawn about the STRIDE regimen in comparison with durvalumab as a single agent, because the trial was not powered for that.

The STRIDE regimen showed a lower risk of bleeding in comparison with combinations that include VEGF inhibitors (such as bevacizumab), he said, but he also pointed out that this trial excluded patients with main portal vein thrombosis, who are at high risk of bleeding.

Details of adverse events

In the NEJM article, the trialists report that grade 3/4 treatment-emergent adverse events occurred in 50.5% of patients with STRIDE, 37.1% with durvalumab alone, and 52.4% of patients with sorafenib.

The manufacturer noted that severe and fatal immune-mediated adverse reactions may occur, including immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, dermatologic reactions, and others.

The company also noted that among the patients with unresectable HCC in the HIMALAYA study who received the STRIDE regimen, the most common adverse reactions (occurring in ≥ 20% of patients) were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain.

Serious adverse reactions occurred in 41% of patients and included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%).

Fatal adverse reactions occurred in 8% of patients who received the combination, including death (1%), intracranial hemorrhage (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%).

Permanent discontinuation of the treatment regimen because of an adverse reaction occurred in 14% of patients.

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

The Food and Drug Administration has approved a new immunotherapy combination for use in the treatment of unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer.

The new combination comprises a single dose of tremelimumab (Imjudo, AstraZeneca) followed by treatment with durvalumab (Imfinzi, AstraZeneca) in what is known as the STRIDE (single-tremelimumab regular-interval durvalumab) regimen.

This marks the first worldwide approval for tremelimumab, which is a CTLA-4 antibody.

The other drug in the combination, durvalumab, is an anti-PDL1 antibody and is already approved by the FDA for use in several tumor types, including lung cancer, bladder cancer, and biliary tract cancers.

The STRIDE regimen is composed of a single 300-mg dose of tremelimumab followed by durvalumab 1,500 mg given every 4 weeks.

This regimen was used in the HIMALAYA phase 3 trial, which was published in June 2022 in the New England Journal of Medicine.

Results from this trial showed that 30% of patients treated with that combination were still alive at 3 years, compared with 20% of patients who were treated with the standard regimen, sorafenib.

“In addition to this regimen demonstrating a favorable 3-year survival rate in the HIMALAYA trial, safety data showed no increase in severe liver toxicity or bleeding risk for the combination, important factors for patients with liver cancer who also have advanced liver disease,” commented the principal investigator of this trial, Ghassan Abou-Alfa, MD, MBA, attending physician at Memorial Sloan Kettering Cancer Center, New York.

“Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival,” he commented in a press release from the drug’s manufacturer, AstraZeneca.

When the results from this trial were presented earlier this year at the ASCO Gastrointestinal Cancers meeting, the discussant for that abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, suggested that the STRIDE regimen offers a new first-line treatment option for patients with advanced HCC.

He also made several comments about the design of the HIMALAYA trial, which has a third treatment arm in which patients received durvalumab alone. Dr. El-Khoueiry noted that single-agent durvalumab was noninferior to sorafenib, but he added that no conclusions could be drawn about the STRIDE regimen in comparison with durvalumab as a single agent, because the trial was not powered for that.

The STRIDE regimen showed a lower risk of bleeding in comparison with combinations that include VEGF inhibitors (such as bevacizumab), he said, but he also pointed out that this trial excluded patients with main portal vein thrombosis, who are at high risk of bleeding.

Details of adverse events

In the NEJM article, the trialists report that grade 3/4 treatment-emergent adverse events occurred in 50.5% of patients with STRIDE, 37.1% with durvalumab alone, and 52.4% of patients with sorafenib.

The manufacturer noted that severe and fatal immune-mediated adverse reactions may occur, including immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, dermatologic reactions, and others.

The company also noted that among the patients with unresectable HCC in the HIMALAYA study who received the STRIDE regimen, the most common adverse reactions (occurring in ≥ 20% of patients) were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain.

Serious adverse reactions occurred in 41% of patients and included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%).

Fatal adverse reactions occurred in 8% of patients who received the combination, including death (1%), intracranial hemorrhage (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%).

Permanent discontinuation of the treatment regimen because of an adverse reaction occurred in 14% of patients.

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

The Food and Drug Administration has approved a new immunotherapy combination for use in the treatment of unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer.

The new combination comprises a single dose of tremelimumab (Imjudo, AstraZeneca) followed by treatment with durvalumab (Imfinzi, AstraZeneca) in what is known as the STRIDE (single-tremelimumab regular-interval durvalumab) regimen.

This marks the first worldwide approval for tremelimumab, which is a CTLA-4 antibody.

The other drug in the combination, durvalumab, is an anti-PDL1 antibody and is already approved by the FDA for use in several tumor types, including lung cancer, bladder cancer, and biliary tract cancers.

The STRIDE regimen is composed of a single 300-mg dose of tremelimumab followed by durvalumab 1,500 mg given every 4 weeks.

This regimen was used in the HIMALAYA phase 3 trial, which was published in June 2022 in the New England Journal of Medicine.

Results from this trial showed that 30% of patients treated with that combination were still alive at 3 years, compared with 20% of patients who were treated with the standard regimen, sorafenib.

“In addition to this regimen demonstrating a favorable 3-year survival rate in the HIMALAYA trial, safety data showed no increase in severe liver toxicity or bleeding risk for the combination, important factors for patients with liver cancer who also have advanced liver disease,” commented the principal investigator of this trial, Ghassan Abou-Alfa, MD, MBA, attending physician at Memorial Sloan Kettering Cancer Center, New York.

“Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival,” he commented in a press release from the drug’s manufacturer, AstraZeneca.

When the results from this trial were presented earlier this year at the ASCO Gastrointestinal Cancers meeting, the discussant for that abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, suggested that the STRIDE regimen offers a new first-line treatment option for patients with advanced HCC.

He also made several comments about the design of the HIMALAYA trial, which has a third treatment arm in which patients received durvalumab alone. Dr. El-Khoueiry noted that single-agent durvalumab was noninferior to sorafenib, but he added that no conclusions could be drawn about the STRIDE regimen in comparison with durvalumab as a single agent, because the trial was not powered for that.

The STRIDE regimen showed a lower risk of bleeding in comparison with combinations that include VEGF inhibitors (such as bevacizumab), he said, but he also pointed out that this trial excluded patients with main portal vein thrombosis, who are at high risk of bleeding.

Details of adverse events

In the NEJM article, the trialists report that grade 3/4 treatment-emergent adverse events occurred in 50.5% of patients with STRIDE, 37.1% with durvalumab alone, and 52.4% of patients with sorafenib.

The manufacturer noted that severe and fatal immune-mediated adverse reactions may occur, including immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, dermatologic reactions, and others.

The company also noted that among the patients with unresectable HCC in the HIMALAYA study who received the STRIDE regimen, the most common adverse reactions (occurring in ≥ 20% of patients) were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain.

Serious adverse reactions occurred in 41% of patients and included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%).

Fatal adverse reactions occurred in 8% of patients who received the combination, including death (1%), intracranial hemorrhage (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%).

Permanent discontinuation of the treatment regimen because of an adverse reaction occurred in 14% of patients.

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

Cardiovascular health (CVH) scores that include sleep predicted CV disease risk among older U.S. adults, supporting the American Heart Association’s recent inclusion of sleep in its own checklist.

Sleep duration is now considered “an essential component for ideal heart and brain health,” according to the AHA’s updated checklist, now called Life’s Essential 8. “Our study is the first to show that sleep metrics add independent predictive value for CVD events over and above the original seven cardiovascular health metrics, providing support for updating the guidelines from Life’s Simple 7 (LS7) to Life’s Essential 8,” lead author Nour Makarem, PhD, of the Mailman School of Public Health at Columbia University Irving Medical Center, New York, said in an interview.

For the study, her team compared four versions of LS7 checklists that included sleep in relation to cardiovascular disease (CVD) risk.

“CVH scores that included sleep duration alone as a measure of overall sleep health, as well as scores that included multiple dimensions of sleep health (that is, sleep duration, efficiency, and regularity, daytime sleepiness, and sleep disorders), were both predictive of future CVD,” she said.

Study participants scoring in the highest tertile of the CVH checklists that included sleep had up to a 47% lower CVD risk.

Sleeping 7 hours or more but less than 9 hours nightly was considered “ideal,” according to the study, which was published online  in the Journal of the American Heart Association.
 

Lower the odds

Dr. Makarem and colleagues analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis (MESA) sleep study using overnight polysomnography, 7-day wrist actigraphy, validated questionnaires, and outcomes. They used the data to evaluate the four iterations of an expanded LS7 score:

• Score 1 included sleep duration;
• Score 2 included sleep characteristics linked to CVD in the literature (sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnea [OSA]);
• Score 3 included sleep characteristics associated with CVD in MESA (sleep duration and efficiency, daytime sleepiness, and OSA); and
• Score 4, also based on CVD in MESA, included sleep regularity.

Among 1,920 participants (mean age 69 years; 54% women; 40%, White individuals), the mean LS7 score was 7.3, and the means of the alternate CVH scores that included sleep ranged from 7.4 to 7.8 (scores range from 0 to 14, with higher scores indicating better CVH).

On actigraphy, 63% of participants slept less than 7 hours; 30% slept less than 6 hours; 39% had high night-to-night variability in sleep duration; and 25% had high variability in sleep onset timing.

Overall, 10% had sleep efficiency less than 85%; 14% had excessive daytime sleepiness; 36% had high insomnia symptoms; and 47% had moderate to severe OSA. Short-duration sleepers also had a higher prevalence of overweight/obesity, diabetes, and hypertension and had lower mean LS7 scores.

During a mean follow-up of 4.4 years, 95 prevalent CVD events and 93 incident cases occurred.

Higher scores on all four expanded versions were related to lower odds of having CVD. Participants in the highest versus the lowest tertile of the LS7 score had 75% lower CVD odds (odds ratio, 0.25). Similarly, those in the highest versus the lowest tertile of CVH scores 1 and 2 had 71% and 80% lower odds of prevalent CVD (OR, 0.29 and OR, 0.20), respectively.

Overall, participants in the highest versus lowest tertile of the LS7 score and all CVH scores had up to 80% lower odds of prevalent CVD; those in the highest versus lowest tertile of CVH score 1, which included sleep duration, and CVH score 4, which included multidimensional sleep health, had 43% and 47% lower incident CVD risk (hazard ratios, 0.57 and 0.53), respectively.

The LS7 score alone was not significantly associated with CVD incidence (HR, 0.62).

“Clinicians should ask patients about their sleep health and emphasize the importance of prioritizing sleep for heart disease prevention,” Dr. Makarem said.
 

Sleep ‘devalued’

“The sleep field has been fighting to get more sleep education into medical education for decades,” AHA volunteer expert Michael A. Grandner, PhD, Director of the Sleep & Health Research Program and of the Behavioral Sleep Medicine Clinic at the University of Arizona College of Medicine, Tucson, said in an interview.

“To my knowledge, there still is not a lot of attention given to it, partly because the culture in medical school and among residents is one of not sleeping,” said Dr. Grandner, who was not involved in the study. “The culture among physicians is ‘Who needs sleep? I function fine without it.’ ”

“Sleep made it to the checklist because it is a biological requirement for human life,” he noted. “We sleep for the same reason we breathe and drink. It’s an imperative. Yet we live in a society that devalues sleep.”

It’s “extremely unusual” for a doctor to ask a patient how they’re sleeping, he said. “It’s also pretty unusual to have sleep-related conversations between doctors and patients, especially in the context of health, not just, ‘Hey, doc, I can’t sleep, throw me a pill.’”

Clinicians should be asking every patient about how they’re sleeping at every visit, Dr. Grandner said. “It’s now part of the official definition of heart health. Just like you would be remiss if you didn’t ask about smoking or test blood pressure, you’d be missing something important by not asking about sleep – something that has similar billing to diet, exercise, blood pressure, and all the other ‘essentials.’ ”

No commercial funding or conflicts of interest were declared.

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

Cardiovascular health (CVH) scores that include sleep predicted CV disease risk among older U.S. adults, supporting the American Heart Association’s recent inclusion of sleep in its own checklist.

Sleep duration is now considered “an essential component for ideal heart and brain health,” according to the AHA’s updated checklist, now called Life’s Essential 8. “Our study is the first to show that sleep metrics add independent predictive value for CVD events over and above the original seven cardiovascular health metrics, providing support for updating the guidelines from Life’s Simple 7 (LS7) to Life’s Essential 8,” lead author Nour Makarem, PhD, of the Mailman School of Public Health at Columbia University Irving Medical Center, New York, said in an interview.

For the study, her team compared four versions of LS7 checklists that included sleep in relation to cardiovascular disease (CVD) risk.

“CVH scores that included sleep duration alone as a measure of overall sleep health, as well as scores that included multiple dimensions of sleep health (that is, sleep duration, efficiency, and regularity, daytime sleepiness, and sleep disorders), were both predictive of future CVD,” she said.

Study participants scoring in the highest tertile of the CVH checklists that included sleep had up to a 47% lower CVD risk.

Sleeping 7 hours or more but less than 9 hours nightly was considered “ideal,” according to the study, which was published online  in the Journal of the American Heart Association.
 

Lower the odds

Dr. Makarem and colleagues analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis (MESA) sleep study using overnight polysomnography, 7-day wrist actigraphy, validated questionnaires, and outcomes. They used the data to evaluate the four iterations of an expanded LS7 score:

• Score 1 included sleep duration;
• Score 2 included sleep characteristics linked to CVD in the literature (sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnea [OSA]);
• Score 3 included sleep characteristics associated with CVD in MESA (sleep duration and efficiency, daytime sleepiness, and OSA); and
• Score 4, also based on CVD in MESA, included sleep regularity.

Among 1,920 participants (mean age 69 years; 54% women; 40%, White individuals), the mean LS7 score was 7.3, and the means of the alternate CVH scores that included sleep ranged from 7.4 to 7.8 (scores range from 0 to 14, with higher scores indicating better CVH).

On actigraphy, 63% of participants slept less than 7 hours; 30% slept less than 6 hours; 39% had high night-to-night variability in sleep duration; and 25% had high variability in sleep onset timing.

Overall, 10% had sleep efficiency less than 85%; 14% had excessive daytime sleepiness; 36% had high insomnia symptoms; and 47% had moderate to severe OSA. Short-duration sleepers also had a higher prevalence of overweight/obesity, diabetes, and hypertension and had lower mean LS7 scores.

During a mean follow-up of 4.4 years, 95 prevalent CVD events and 93 incident cases occurred.

Higher scores on all four expanded versions were related to lower odds of having CVD. Participants in the highest versus the lowest tertile of the LS7 score had 75% lower CVD odds (odds ratio, 0.25). Similarly, those in the highest versus the lowest tertile of CVH scores 1 and 2 had 71% and 80% lower odds of prevalent CVD (OR, 0.29 and OR, 0.20), respectively.

Overall, participants in the highest versus lowest tertile of the LS7 score and all CVH scores had up to 80% lower odds of prevalent CVD; those in the highest versus lowest tertile of CVH score 1, which included sleep duration, and CVH score 4, which included multidimensional sleep health, had 43% and 47% lower incident CVD risk (hazard ratios, 0.57 and 0.53), respectively.

The LS7 score alone was not significantly associated with CVD incidence (HR, 0.62).

“Clinicians should ask patients about their sleep health and emphasize the importance of prioritizing sleep for heart disease prevention,” Dr. Makarem said.
 

Sleep ‘devalued’

“The sleep field has been fighting to get more sleep education into medical education for decades,” AHA volunteer expert Michael A. Grandner, PhD, Director of the Sleep & Health Research Program and of the Behavioral Sleep Medicine Clinic at the University of Arizona College of Medicine, Tucson, said in an interview.

“To my knowledge, there still is not a lot of attention given to it, partly because the culture in medical school and among residents is one of not sleeping,” said Dr. Grandner, who was not involved in the study. “The culture among physicians is ‘Who needs sleep? I function fine without it.’ ”

“Sleep made it to the checklist because it is a biological requirement for human life,” he noted. “We sleep for the same reason we breathe and drink. It’s an imperative. Yet we live in a society that devalues sleep.”

It’s “extremely unusual” for a doctor to ask a patient how they’re sleeping, he said. “It’s also pretty unusual to have sleep-related conversations between doctors and patients, especially in the context of health, not just, ‘Hey, doc, I can’t sleep, throw me a pill.’”

Clinicians should be asking every patient about how they’re sleeping at every visit, Dr. Grandner said. “It’s now part of the official definition of heart health. Just like you would be remiss if you didn’t ask about smoking or test blood pressure, you’d be missing something important by not asking about sleep – something that has similar billing to diet, exercise, blood pressure, and all the other ‘essentials.’ ”

No commercial funding or conflicts of interest were declared.

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

Cardiovascular health (CVH) scores that include sleep predicted CV disease risk among older U.S. adults, supporting the American Heart Association’s recent inclusion of sleep in its own checklist.

Sleep duration is now considered “an essential component for ideal heart and brain health,” according to the AHA’s updated checklist, now called Life’s Essential 8. “Our study is the first to show that sleep metrics add independent predictive value for CVD events over and above the original seven cardiovascular health metrics, providing support for updating the guidelines from Life’s Simple 7 (LS7) to Life’s Essential 8,” lead author Nour Makarem, PhD, of the Mailman School of Public Health at Columbia University Irving Medical Center, New York, said in an interview.

For the study, her team compared four versions of LS7 checklists that included sleep in relation to cardiovascular disease (CVD) risk.

“CVH scores that included sleep duration alone as a measure of overall sleep health, as well as scores that included multiple dimensions of sleep health (that is, sleep duration, efficiency, and regularity, daytime sleepiness, and sleep disorders), were both predictive of future CVD,” she said.

Study participants scoring in the highest tertile of the CVH checklists that included sleep had up to a 47% lower CVD risk.

Sleeping 7 hours or more but less than 9 hours nightly was considered “ideal,” according to the study, which was published online  in the Journal of the American Heart Association.
 

Lower the odds

Dr. Makarem and colleagues analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis (MESA) sleep study using overnight polysomnography, 7-day wrist actigraphy, validated questionnaires, and outcomes. They used the data to evaluate the four iterations of an expanded LS7 score:

• Score 1 included sleep duration;
• Score 2 included sleep characteristics linked to CVD in the literature (sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnea [OSA]);
• Score 3 included sleep characteristics associated with CVD in MESA (sleep duration and efficiency, daytime sleepiness, and OSA); and
• Score 4, also based on CVD in MESA, included sleep regularity.

Among 1,920 participants (mean age 69 years; 54% women; 40%, White individuals), the mean LS7 score was 7.3, and the means of the alternate CVH scores that included sleep ranged from 7.4 to 7.8 (scores range from 0 to 14, with higher scores indicating better CVH).

On actigraphy, 63% of participants slept less than 7 hours; 30% slept less than 6 hours; 39% had high night-to-night variability in sleep duration; and 25% had high variability in sleep onset timing.

Overall, 10% had sleep efficiency less than 85%; 14% had excessive daytime sleepiness; 36% had high insomnia symptoms; and 47% had moderate to severe OSA. Short-duration sleepers also had a higher prevalence of overweight/obesity, diabetes, and hypertension and had lower mean LS7 scores.

During a mean follow-up of 4.4 years, 95 prevalent CVD events and 93 incident cases occurred.

Higher scores on all four expanded versions were related to lower odds of having CVD. Participants in the highest versus the lowest tertile of the LS7 score had 75% lower CVD odds (odds ratio, 0.25). Similarly, those in the highest versus the lowest tertile of CVH scores 1 and 2 had 71% and 80% lower odds of prevalent CVD (OR, 0.29 and OR, 0.20), respectively.

Overall, participants in the highest versus lowest tertile of the LS7 score and all CVH scores had up to 80% lower odds of prevalent CVD; those in the highest versus lowest tertile of CVH score 1, which included sleep duration, and CVH score 4, which included multidimensional sleep health, had 43% and 47% lower incident CVD risk (hazard ratios, 0.57 and 0.53), respectively.

The LS7 score alone was not significantly associated with CVD incidence (HR, 0.62).

“Clinicians should ask patients about their sleep health and emphasize the importance of prioritizing sleep for heart disease prevention,” Dr. Makarem said.
 

Sleep ‘devalued’

“The sleep field has been fighting to get more sleep education into medical education for decades,” AHA volunteer expert Michael A. Grandner, PhD, Director of the Sleep & Health Research Program and of the Behavioral Sleep Medicine Clinic at the University of Arizona College of Medicine, Tucson, said in an interview.

“To my knowledge, there still is not a lot of attention given to it, partly because the culture in medical school and among residents is one of not sleeping,” said Dr. Grandner, who was not involved in the study. “The culture among physicians is ‘Who needs sleep? I function fine without it.’ ”

“Sleep made it to the checklist because it is a biological requirement for human life,” he noted. “We sleep for the same reason we breathe and drink. It’s an imperative. Yet we live in a society that devalues sleep.”

It’s “extremely unusual” for a doctor to ask a patient how they’re sleeping, he said. “It’s also pretty unusual to have sleep-related conversations between doctors and patients, especially in the context of health, not just, ‘Hey, doc, I can’t sleep, throw me a pill.’”

Clinicians should be asking every patient about how they’re sleeping at every visit, Dr. Grandner said. “It’s now part of the official definition of heart health. Just like you would be remiss if you didn’t ask about smoking or test blood pressure, you’d be missing something important by not asking about sleep – something that has similar billing to diet, exercise, blood pressure, and all the other ‘essentials.’ ”

No commercial funding or conflicts of interest were declared.

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

Key clinical point: In patients receiving atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP) responses of 50% and 20% served as predictors of overall response rate (ORR) and disease control rate (DCR), respectively, with both responses being associated with progression-free survival (PFS).

Major finding: An AFP relative decrease of ≥50% was associated with ORR (odds ratio 5.7; 95% CI 1.9-17) and PFS (hazard ratio [HR] 5.60; P  =  .006), whereas that of ≥20% was associated with DCR (positive predictive value 100%; sensitivity 52.0%) and PFS (HR 4.44; P < .001).

Study details: This multicenter prospective study included 91 patients with unresectable HCC and AFP ≥10 ng/mL who were treated with atezolizumab and bevacizumab.

Disclosures: This study was supported by the Japan Agency for Medical Research and Development. Two authors declared receiving lecture fees from a pharmaceutical company.

Source: Tamaki N et al. Optimal threshold of alpha-fetoprotein response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab. Invest New Drugs. 2022 (Sep 24). Doi: 10.1007/s10637-022-01303-w

Key clinical point: In patients receiving atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP) responses of 50% and 20% served as predictors of overall response rate (ORR) and disease control rate (DCR), respectively, with both responses being associated with progression-free survival (PFS).

Major finding: An AFP relative decrease of ≥50% was associated with ORR (odds ratio 5.7; 95% CI 1.9-17) and PFS (hazard ratio [HR] 5.60; P  =  .006), whereas that of ≥20% was associated with DCR (positive predictive value 100%; sensitivity 52.0%) and PFS (HR 4.44; P < .001).

Study details: This multicenter prospective study included 91 patients with unresectable HCC and AFP ≥10 ng/mL who were treated with atezolizumab and bevacizumab.

Disclosures: This study was supported by the Japan Agency for Medical Research and Development. Two authors declared receiving lecture fees from a pharmaceutical company.

Source: Tamaki N et al. Optimal threshold of alpha-fetoprotein response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab. Invest New Drugs. 2022 (Sep 24). Doi: 10.1007/s10637-022-01303-w

Key clinical point: In patients receiving atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP) responses of 50% and 20% served as predictors of overall response rate (ORR) and disease control rate (DCR), respectively, with both responses being associated with progression-free survival (PFS).

Major finding: An AFP relative decrease of ≥50% was associated with ORR (odds ratio 5.7; 95% CI 1.9-17) and PFS (hazard ratio [HR] 5.60; P  =  .006), whereas that of ≥20% was associated with DCR (positive predictive value 100%; sensitivity 52.0%) and PFS (HR 4.44; P < .001).

Study details: This multicenter prospective study included 91 patients with unresectable HCC and AFP ≥10 ng/mL who were treated with atezolizumab and bevacizumab.

Disclosures: This study was supported by the Japan Agency for Medical Research and Development. Two authors declared receiving lecture fees from a pharmaceutical company.

Source: Tamaki N et al. Optimal threshold of alpha-fetoprotein response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab. Invest New Drugs. 2022 (Sep 24). Doi: 10.1007/s10637-022-01303-w

Key clinical point: Cirrhosis is often unrecognized in patients diagnosed with hepatocellular carcinoma (HCC). Unrecognized cirrhosis is associated with more advanced HCC at diagnosis and a worse prognosis.

Major finding: Patients with unrecognized cirrhosis vs those with known cirrhosis diagnosed with HCC under surveillance had a significantly shorter median survival (0.89 years [95% CI 0.78-1.01] vs 3.79 years [95% CI 3.19-4.39]) and a higher mortality rate (adjusted hazard ratio 2.36; 95% CI 2.09-2.66).

Study details: This retrospective cohort study included 2670 adult patients with HCC and liver cirrhosis, of which 1033 had unrecognized cirrhosis at HCC diagnosis and 901 had known cirrhosis with HCC diagnosed under surveillance.

Disclosures: No source of funding was disclosed. The authors declared no conflicts of interest.

Source: Vaz J et al. Unrecognized liver cirrhosis is common and associated with worse survival in hepatocellular carcinoma: A nationwide cohort study of 3473 patients. J Intern Med. 2022 (Sep 27). Doi: 10.1111/joim.13570

Key clinical point: Cirrhosis is often unrecognized in patients diagnosed with hepatocellular carcinoma (HCC). Unrecognized cirrhosis is associated with more advanced HCC at diagnosis and a worse prognosis.

Major finding: Patients with unrecognized cirrhosis vs those with known cirrhosis diagnosed with HCC under surveillance had a significantly shorter median survival (0.89 years [95% CI 0.78-1.01] vs 3.79 years [95% CI 3.19-4.39]) and a higher mortality rate (adjusted hazard ratio 2.36; 95% CI 2.09-2.66).

Study details: This retrospective cohort study included 2670 adult patients with HCC and liver cirrhosis, of which 1033 had unrecognized cirrhosis at HCC diagnosis and 901 had known cirrhosis with HCC diagnosed under surveillance.

Disclosures: No source of funding was disclosed. The authors declared no conflicts of interest.

Source: Vaz J et al. Unrecognized liver cirrhosis is common and associated with worse survival in hepatocellular carcinoma: A nationwide cohort study of 3473 patients. J Intern Med. 2022 (Sep 27). Doi: 10.1111/joim.13570

Key clinical point: Cirrhosis is often unrecognized in patients diagnosed with hepatocellular carcinoma (HCC). Unrecognized cirrhosis is associated with more advanced HCC at diagnosis and a worse prognosis.

Major finding: Patients with unrecognized cirrhosis vs those with known cirrhosis diagnosed with HCC under surveillance had a significantly shorter median survival (0.89 years [95% CI 0.78-1.01] vs 3.79 years [95% CI 3.19-4.39]) and a higher mortality rate (adjusted hazard ratio 2.36; 95% CI 2.09-2.66).

Study details: This retrospective cohort study included 2670 adult patients with HCC and liver cirrhosis, of which 1033 had unrecognized cirrhosis at HCC diagnosis and 901 had known cirrhosis with HCC diagnosed under surveillance.

Disclosures: No source of funding was disclosed. The authors declared no conflicts of interest.

Source: Vaz J et al. Unrecognized liver cirrhosis is common and associated with worse survival in hepatocellular carcinoma: A nationwide cohort study of 3473 patients. J Intern Med. 2022 (Sep 27). Doi: 10.1111/joim.13570