TOPLINE:

The Million Hearts Model, a U.S. Centers for Medicare & Medicaid Services (CMS) initiative that encouraged and paid health care organizations to assess and reduce cardiovascular disease (CVD) risk, reduced first-time myocardial infarction (MI) and strokes among Medicare beneficiaries without significant changes in Medicare spending, a randomized trial finds.

METHODOLOGY:

• Researchers assessed the Million Hearts CVD Risk Reduction Model in a pragmatic, cluster-randomized trial among 342 health care organizations – half in the intervention group and half in the standard care control group.
• Among 218,684 medium- or high-risk Medicare beneficiaries (median age, 72 years), 130,578 were in the intervention group in which Medicare paid for guideline-concordant care including routine CVD risk assessment, and 88,286 were in the standard care group.
• Outcomes included first time CVD events (for instance, MI, stroke, transient ischemic attack), combined first-time CVD events and CVD deaths, and Medicare spending.

TAKEAWAY:

• Over a median follow-up of 4.3 years, the intervention group had a 3.3% lower rate of CVD events than the control group (adjusted hazard ratio, 0.97; 90% confidence interval, 0.93-1.00; P = .09) and a 4.2% lower rate of combined first-time CVD events and CVD deaths (HR, 0.96; 90% CI, 0.93-0.99; P = .02).
• These relative effects represent an absolute re.duction of 0.3 percentage points in the probability of a CVD event over 5 years (7.8% intervention vs 8.1%) and 0.4 percentage points in the probability of a CVD event or CVD death over 5 years (9.3% intervention vs. 9.7% control).
• The intervention group also had a 4.3% lower death rate (HR, 0.96; 90% CI, 0.93-0.98; P = .01; absolute reduction of 0.5 percentage points over 5 years).
• Analyses by cause of death showed the largest relative declines (10.6%) among deaths due to coronary heart disease and CVD.
• There was no significant between-group difference in Medicare spending on CVD events or in overall Medicare Parts A and B spending.

IN PRACTICE:

“The model was unique in paying for overall CVD risk reduction, measured by a novel, longitudinal risk calculator, rather than tying performance-based payments to control of individual risk factors,” the authors write.

“The encouraging findings from the Million Hearts Model suggest that modernized payment models may be an affirmative strategy to [incentivize guideline-concordant CVD preventive care and improve outcomes], though further work is needed to ensure that these models are patient-centric, optimally deployed, and equity-enhancing,” add the editorial writers.

SOURCE:

The study, with first author Laura Blue, PhD, Mathematica, Washington, was published online in JAMA, with an accompanying editorial.

LIMITATIONS:

The main limitation is nonparticipation of many of the organizations (516 were randomly assigned to one of the study groups, 342 participated) and incomplete entry of beneficiary data into the registry, which could have led to systematic differences between the two groups. Bias due to the selective participation of organizations and beneficiaries cannot be ruled out.

DISCLOSURES:

Funding for the study was provided by CMS, Department of Health & Human Services. The authors have disclosed no relevant financial relationships.

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

TOPLINE:

The Million Hearts Model, a U.S. Centers for Medicare & Medicaid Services (CMS) initiative that encouraged and paid health care organizations to assess and reduce cardiovascular disease (CVD) risk, reduced first-time myocardial infarction (MI) and strokes among Medicare beneficiaries without significant changes in Medicare spending, a randomized trial finds.

METHODOLOGY:

• Researchers assessed the Million Hearts CVD Risk Reduction Model in a pragmatic, cluster-randomized trial among 342 health care organizations – half in the intervention group and half in the standard care control group.
• Among 218,684 medium- or high-risk Medicare beneficiaries (median age, 72 years), 130,578 were in the intervention group in which Medicare paid for guideline-concordant care including routine CVD risk assessment, and 88,286 were in the standard care group.
• Outcomes included first time CVD events (for instance, MI, stroke, transient ischemic attack), combined first-time CVD events and CVD deaths, and Medicare spending.

TAKEAWAY:

• Over a median follow-up of 4.3 years, the intervention group had a 3.3% lower rate of CVD events than the control group (adjusted hazard ratio, 0.97; 90% confidence interval, 0.93-1.00; P = .09) and a 4.2% lower rate of combined first-time CVD events and CVD deaths (HR, 0.96; 90% CI, 0.93-0.99; P = .02).
• These relative effects represent an absolute re.duction of 0.3 percentage points in the probability of a CVD event over 5 years (7.8% intervention vs 8.1%) and 0.4 percentage points in the probability of a CVD event or CVD death over 5 years (9.3% intervention vs. 9.7% control).
• The intervention group also had a 4.3% lower death rate (HR, 0.96; 90% CI, 0.93-0.98; P = .01; absolute reduction of 0.5 percentage points over 5 years).
• Analyses by cause of death showed the largest relative declines (10.6%) among deaths due to coronary heart disease and CVD.
• There was no significant between-group difference in Medicare spending on CVD events or in overall Medicare Parts A and B spending.

IN PRACTICE:

“The model was unique in paying for overall CVD risk reduction, measured by a novel, longitudinal risk calculator, rather than tying performance-based payments to control of individual risk factors,” the authors write.

“The encouraging findings from the Million Hearts Model suggest that modernized payment models may be an affirmative strategy to [incentivize guideline-concordant CVD preventive care and improve outcomes], though further work is needed to ensure that these models are patient-centric, optimally deployed, and equity-enhancing,” add the editorial writers.

SOURCE:

The study, with first author Laura Blue, PhD, Mathematica, Washington, was published online in JAMA, with an accompanying editorial.

LIMITATIONS:

The main limitation is nonparticipation of many of the organizations (516 were randomly assigned to one of the study groups, 342 participated) and incomplete entry of beneficiary data into the registry, which could have led to systematic differences between the two groups. Bias due to the selective participation of organizations and beneficiaries cannot be ruled out.

DISCLOSURES:

Funding for the study was provided by CMS, Department of Health & Human Services. The authors have disclosed no relevant financial relationships.

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

TOPLINE:

The Million Hearts Model, a U.S. Centers for Medicare & Medicaid Services (CMS) initiative that encouraged and paid health care organizations to assess and reduce cardiovascular disease (CVD) risk, reduced first-time myocardial infarction (MI) and strokes among Medicare beneficiaries without significant changes in Medicare spending, a randomized trial finds.

METHODOLOGY:

• Researchers assessed the Million Hearts CVD Risk Reduction Model in a pragmatic, cluster-randomized trial among 342 health care organizations – half in the intervention group and half in the standard care control group.
• Among 218,684 medium- or high-risk Medicare beneficiaries (median age, 72 years), 130,578 were in the intervention group in which Medicare paid for guideline-concordant care including routine CVD risk assessment, and 88,286 were in the standard care group.
• Outcomes included first time CVD events (for instance, MI, stroke, transient ischemic attack), combined first-time CVD events and CVD deaths, and Medicare spending.

TAKEAWAY:

• Over a median follow-up of 4.3 years, the intervention group had a 3.3% lower rate of CVD events than the control group (adjusted hazard ratio, 0.97; 90% confidence interval, 0.93-1.00; P = .09) and a 4.2% lower rate of combined first-time CVD events and CVD deaths (HR, 0.96; 90% CI, 0.93-0.99; P = .02).
• These relative effects represent an absolute re.duction of 0.3 percentage points in the probability of a CVD event over 5 years (7.8% intervention vs 8.1%) and 0.4 percentage points in the probability of a CVD event or CVD death over 5 years (9.3% intervention vs. 9.7% control).
• The intervention group also had a 4.3% lower death rate (HR, 0.96; 90% CI, 0.93-0.98; P = .01; absolute reduction of 0.5 percentage points over 5 years).
• Analyses by cause of death showed the largest relative declines (10.6%) among deaths due to coronary heart disease and CVD.
• There was no significant between-group difference in Medicare spending on CVD events or in overall Medicare Parts A and B spending.

IN PRACTICE:

“The model was unique in paying for overall CVD risk reduction, measured by a novel, longitudinal risk calculator, rather than tying performance-based payments to control of individual risk factors,” the authors write.

“The encouraging findings from the Million Hearts Model suggest that modernized payment models may be an affirmative strategy to [incentivize guideline-concordant CVD preventive care and improve outcomes], though further work is needed to ensure that these models are patient-centric, optimally deployed, and equity-enhancing,” add the editorial writers.

SOURCE:

The study, with first author Laura Blue, PhD, Mathematica, Washington, was published online in JAMA, with an accompanying editorial.

LIMITATIONS:

The main limitation is nonparticipation of many of the organizations (516 were randomly assigned to one of the study groups, 342 participated) and incomplete entry of beneficiary data into the registry, which could have led to systematic differences between the two groups. Bias due to the selective participation of organizations and beneficiaries cannot be ruled out.

DISCLOSURES:

Funding for the study was provided by CMS, Department of Health & Human Services. The authors have disclosed no relevant financial relationships.

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

MADRID – Research presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2023 underline the benefit of adding immunotherapy to chemotherapy in advanced or recurrent endometrial cancer, and question whether adding the PARP inhibitor olaparib to the chemo-immunotherapy combination could provide further benefit.

In the AtTEnd trial, presented on Oct. 21, more than 550 patients with advanced newly diagnosed or recurrent disease were randomized to the antiprogrammed death–ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) or placebo plus chemotherapy followed by maintenance atezolizumab or placebo.

Adding immunotherapy to chemotherapy improved progression-free survival (PFS) among all-comers – 28.1% vs. 17% at 2 years. The PFS benefit was much more pronounced among patients with mismatch repair-deficient (dMMR) disease – 50.4% vs. 16% at 2 years. Mismatch repair-deficient disease patients receiving atezolizumab also demonstrated an early overall survival benefit, according to findings from the interim analysis.

In the DUO-E trial, presented during the same Oct. 21 session, nearly 720 patients with newly diagnosed advanced or recurrent endometrial cancer were randomized to one of three groups: Chemotherapy alone with maintenance placebo, chemotherapy plus durvalumab (Imfinzi) with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab and the PARP inhibitor olaparib.

The results, published simultaneously in the Journal of Clinical Oncology, showed that adding durvalumab to chemotherapy followed by maintenance durvalumab with or without olaparib led to a significant improvement in PFS, compared with chemotherapy alone. As in the AtTEnd trial, this PFS was also more pronounced in dMMR patients.

Overall, Andrés Cervantes, MD, PhD, from the University of Valencia, Spain, and president of ESMO, explained that this research marks “very positive data for women with gynecological cancers,” with immunotherapy now incorporated into the standard of care.

However, an expert questioned whether the DUO-E trial clearly demonstrated the benefit of adding olaparib to immuno- and chemotherapy and whether certain subsets of patients may be more likely to benefit from the PARP inhibitor.
 

Inside AtTEnd

A growing body of research has shown that single agent immunotherapy is effective in treating endometrial cancer, particularly in tumors with dMMR, and that immunotherapy and chemotherapy may have a synergistic effect.

David S. P. Tan, MD, PhD, National University Cancer Institute, Singapore, who was not involved in the studies, commented that “the molecular classification of endometrial cancer is now leading us to areas that we didn’t think before [were] possible.”

The rationale for combining immunotherapy with chemotherapy, Dr. Tan explained, is that “the cytotoxicity you get from chemotherapy is partly dependent on immune activity within the tumor, and so it makes sense” to combine them.

This approach was borne out by recent positive PFS results from the NRG-GY018 trial of pembrolizumab plus chemotherapy in advanced endometrial cancer as well as from the RUBY trial of dostarlimab in primary advanced or recurrent disease.

To further investigate this chemo-immunotherapy strategy, the AtTEnd team enrolled patients with newly diagnosed or recurrent stage III-IV disease who had received no prior systemic chemotherapy for recurrence within the previous 6 months.

Overall, 551 patients from 89 sites across 10 countries were randomized to standard first-line chemotherapy – carboplatin plus paclitaxel – with either atezolizumab or placebo, followed by maintenance atezolizumab or placebo, which continued until confirmed disease progression.

The median age in the intention-to-treat population was 64-67 years. Nearly 23% of patients had dMMR tumors, and 67.2% had recurrent disease.

The baseline characteristics were well balanced and distributed between arms in the dMMR and all-comers population, said Nicoletta Colombo, MD, University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Italy, who presented the findings at ESMO.

Over a median follow up of 26.2 months, Dr. Colombo and colleagues observed a statistically significant improvement in PFS in the dMMR arm in favor of atezolizumab (hazard ratio, 0.36; P = .0005). At 2 years, 50.4% of patients receiving the immunotherapy were progression-free, compared with 16.0% in the placebo arm.

In all-comers, the PFS improvement with atezolizumab was less pronounced but remained significant (HR, 0.74; P = .0219).

A secondary analysis revealed, among dMMR patients, atezolizumab was associated with an overall survival advantage over placebo (HR, 0.41), with 75% of patients still alive at 2 years vs. 54.2% in the placebo arm. Dr. Colombo also noted a “clear trend” for improved overall survival with atezolizumab as well (HR, 0.82; P = .0483), but no PFS or overall survival benefit was seen with atezolizumab in MMR proficient (pMMR) patients.

Dr. Colombo said the safety profile of atezolizumab plus chemotherapy was “manageable,” with no differences in the rates of “major side effects,” although there was an increase in the rate of treatment-related grade ≥ 3 adverse events in the atezolizumab group (25.8% vs. 14.1%).

Dr. Tan noted that the AtTEnd trial revealed comparable results to earlier trials in this space but underlined that the survival curves in the interim analysis revealed a “red zone” of dMMR patients who do not respond to the combination and in whom immunotherapy is “not sufficient.”

Alongside this, Dr. Tan flagged a “blue zone” of dMMR patients who plateaued in both PFS and overall survival after 2 years. The question for these patients at this point is whether they need to continue immunotherapy beyond 24 months, he said.

But overall, Dr. Tan noted, the AtTEnd data “continue to validate practice-changing therapy for dMMR endometrial cancer patients” with immunotherapy plus chemotherapy, with the lack of benefit in pMMR disease underscoring an “unmet medical need.”
 

Inside DUO-E

The burning question, however, was whether adding a PARP inhibitor to immunotherapy and chemotherapy would boost the survival outcomes further.

The DUO-E trial involved patients with newly diagnosed stage III/IV or recurrent endometrial cancer who had not received systematic therapy for advanced disease and were naive to both PARP inhibitors and immune-mediated therapy.

Overall, 718 patients were randomized to one of three arms: Chemotherapy alone followed by maintenance placebo, chemotherapy plus durvalumab with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab plus olaparib.

Maintenance was continued until disease progression or unacceptable toxicity, or the patients met another discontinuation criteria.

About half of patients were newly diagnosed, half had recurrent disease, and approximately one-fifth had dMMR disease, said Shannon Westin, MD, from the University of Texas MD Anderson Cancer Center, Houston, who presented the findings.

Compared with placebo plus chemotherapy, patients in both the durvalumab alone and durvalumab plus olaparib arms experienced a significant improvement in PFS (HR, 0.71; P = .003; and HR, 0.55; P < .0001, respectively).

This effect was amplified in dMMR patients with durvalumab (HR, 0.42) as well as with durvalumab plus olaparib (HR, 0.41).

In pMMR patients, PFS benefit was stronger in the durvalumab-olaparib arm vs. durvalumab (HR, 0.57 vs. 0.77).

Although the overall survival analysis remains exploratory, Dr. Westin noted a trend toward better overall survival in the two treatment arms vs. placebo (HR, 0.77 with durvalumab, and HR, 0.59 with durvalumab plus olaparib).

However, adding olaparib to the equation increased the rate of grade ≥ 3 adverse events – 67.2% vs. 54.9% with durvalumab and 56.4% with chemotherapy alone in the overall analysis. The addition of olaparib also led to treatment discontinuation in 24.4% of patients vs. 20.9% in the durvalumab arm and 18.6% in the chemotherapy alone arm.

Domenica Lorusso, MD, PhD, who was not involved in the study, commented that the marginal PFS benefit of adding olaparib in DUO-E is “not surprising” because the bar set by immunotherapy is “so high in this population that it’s very difficult” to go any higher.

But the results in pMMR patients reveal “a clear additional benefit” to olaparib, said Dr. Lorusso, from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.

“The main limitation of the trial,” she continued, “is that it was not powered to make a formal comparison between the two experimental arms.”

So, what then is the added benefit of olaparib? “Unfortunately, that remains an unanswered question,” Dr. Lorusso said.

AtTEnd was sponsored by the Mario Negri Institute for Pharmacological Research.

DUO-E was funded by AstraZeneca.

Dr. Colombo declares relationships with AstraZeneca, Clovis Oncology, Esai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Roche, and Novocure.

Dr. Tan declares relationships with AstraZeneca, Karyopharm Therapeutics, Bayer, Roche, MSD, Genmab, Esai, PMV, BioNTech, Ellipses Pharma, Boehringer Ingelheim, Merck Serono, Takeda, and Clovis.

Dr. Westin declares relationships with AstraZeneca, Avenge Bio, Bayer, Bio-Path, Clovis, Genentech/Roche, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, and Zentalis; and consulting and advisory roles for AstraZeneca, Caris, Clovis, Eisai, EQRx, Genentech/Roche, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mersana, Mereo, NGM Bio, Nuvectis, Seagen, Verastem, Vincerx, Zentalis, and ZielBio.

Dr. Lorusso declares relationships with PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis, Tesaro/GSK, Genmab, Immunogen, and Roche.

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

MADRID – Research presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2023 underline the benefit of adding immunotherapy to chemotherapy in advanced or recurrent endometrial cancer, and question whether adding the PARP inhibitor olaparib to the chemo-immunotherapy combination could provide further benefit.

In the AtTEnd trial, presented on Oct. 21, more than 550 patients with advanced newly diagnosed or recurrent disease were randomized to the antiprogrammed death–ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) or placebo plus chemotherapy followed by maintenance atezolizumab or placebo.

Adding immunotherapy to chemotherapy improved progression-free survival (PFS) among all-comers – 28.1% vs. 17% at 2 years. The PFS benefit was much more pronounced among patients with mismatch repair-deficient (dMMR) disease – 50.4% vs. 16% at 2 years. Mismatch repair-deficient disease patients receiving atezolizumab also demonstrated an early overall survival benefit, according to findings from the interim analysis.

In the DUO-E trial, presented during the same Oct. 21 session, nearly 720 patients with newly diagnosed advanced or recurrent endometrial cancer were randomized to one of three groups: Chemotherapy alone with maintenance placebo, chemotherapy plus durvalumab (Imfinzi) with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab and the PARP inhibitor olaparib.

The results, published simultaneously in the Journal of Clinical Oncology, showed that adding durvalumab to chemotherapy followed by maintenance durvalumab with or without olaparib led to a significant improvement in PFS, compared with chemotherapy alone. As in the AtTEnd trial, this PFS was also more pronounced in dMMR patients.

Overall, Andrés Cervantes, MD, PhD, from the University of Valencia, Spain, and president of ESMO, explained that this research marks “very positive data for women with gynecological cancers,” with immunotherapy now incorporated into the standard of care.

However, an expert questioned whether the DUO-E trial clearly demonstrated the benefit of adding olaparib to immuno- and chemotherapy and whether certain subsets of patients may be more likely to benefit from the PARP inhibitor.
 

Inside AtTEnd

A growing body of research has shown that single agent immunotherapy is effective in treating endometrial cancer, particularly in tumors with dMMR, and that immunotherapy and chemotherapy may have a synergistic effect.

David S. P. Tan, MD, PhD, National University Cancer Institute, Singapore, who was not involved in the studies, commented that “the molecular classification of endometrial cancer is now leading us to areas that we didn’t think before [were] possible.”

The rationale for combining immunotherapy with chemotherapy, Dr. Tan explained, is that “the cytotoxicity you get from chemotherapy is partly dependent on immune activity within the tumor, and so it makes sense” to combine them.

This approach was borne out by recent positive PFS results from the NRG-GY018 trial of pembrolizumab plus chemotherapy in advanced endometrial cancer as well as from the RUBY trial of dostarlimab in primary advanced or recurrent disease.

To further investigate this chemo-immunotherapy strategy, the AtTEnd team enrolled patients with newly diagnosed or recurrent stage III-IV disease who had received no prior systemic chemotherapy for recurrence within the previous 6 months.

Overall, 551 patients from 89 sites across 10 countries were randomized to standard first-line chemotherapy – carboplatin plus paclitaxel – with either atezolizumab or placebo, followed by maintenance atezolizumab or placebo, which continued until confirmed disease progression.

The median age in the intention-to-treat population was 64-67 years. Nearly 23% of patients had dMMR tumors, and 67.2% had recurrent disease.

The baseline characteristics were well balanced and distributed between arms in the dMMR and all-comers population, said Nicoletta Colombo, MD, University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Italy, who presented the findings at ESMO.

Over a median follow up of 26.2 months, Dr. Colombo and colleagues observed a statistically significant improvement in PFS in the dMMR arm in favor of atezolizumab (hazard ratio, 0.36; P = .0005). At 2 years, 50.4% of patients receiving the immunotherapy were progression-free, compared with 16.0% in the placebo arm.

In all-comers, the PFS improvement with atezolizumab was less pronounced but remained significant (HR, 0.74; P = .0219).

A secondary analysis revealed, among dMMR patients, atezolizumab was associated with an overall survival advantage over placebo (HR, 0.41), with 75% of patients still alive at 2 years vs. 54.2% in the placebo arm. Dr. Colombo also noted a “clear trend” for improved overall survival with atezolizumab as well (HR, 0.82; P = .0483), but no PFS or overall survival benefit was seen with atezolizumab in MMR proficient (pMMR) patients.

Dr. Colombo said the safety profile of atezolizumab plus chemotherapy was “manageable,” with no differences in the rates of “major side effects,” although there was an increase in the rate of treatment-related grade ≥ 3 adverse events in the atezolizumab group (25.8% vs. 14.1%).

Dr. Tan noted that the AtTEnd trial revealed comparable results to earlier trials in this space but underlined that the survival curves in the interim analysis revealed a “red zone” of dMMR patients who do not respond to the combination and in whom immunotherapy is “not sufficient.”

Alongside this, Dr. Tan flagged a “blue zone” of dMMR patients who plateaued in both PFS and overall survival after 2 years. The question for these patients at this point is whether they need to continue immunotherapy beyond 24 months, he said.

But overall, Dr. Tan noted, the AtTEnd data “continue to validate practice-changing therapy for dMMR endometrial cancer patients” with immunotherapy plus chemotherapy, with the lack of benefit in pMMR disease underscoring an “unmet medical need.”
 

Inside DUO-E

The burning question, however, was whether adding a PARP inhibitor to immunotherapy and chemotherapy would boost the survival outcomes further.

The DUO-E trial involved patients with newly diagnosed stage III/IV or recurrent endometrial cancer who had not received systematic therapy for advanced disease and were naive to both PARP inhibitors and immune-mediated therapy.

Overall, 718 patients were randomized to one of three arms: Chemotherapy alone followed by maintenance placebo, chemotherapy plus durvalumab with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab plus olaparib.

Maintenance was continued until disease progression or unacceptable toxicity, or the patients met another discontinuation criteria.

About half of patients were newly diagnosed, half had recurrent disease, and approximately one-fifth had dMMR disease, said Shannon Westin, MD, from the University of Texas MD Anderson Cancer Center, Houston, who presented the findings.

Compared with placebo plus chemotherapy, patients in both the durvalumab alone and durvalumab plus olaparib arms experienced a significant improvement in PFS (HR, 0.71; P = .003; and HR, 0.55; P < .0001, respectively).

This effect was amplified in dMMR patients with durvalumab (HR, 0.42) as well as with durvalumab plus olaparib (HR, 0.41).

In pMMR patients, PFS benefit was stronger in the durvalumab-olaparib arm vs. durvalumab (HR, 0.57 vs. 0.77).

Although the overall survival analysis remains exploratory, Dr. Westin noted a trend toward better overall survival in the two treatment arms vs. placebo (HR, 0.77 with durvalumab, and HR, 0.59 with durvalumab plus olaparib).

However, adding olaparib to the equation increased the rate of grade ≥ 3 adverse events – 67.2% vs. 54.9% with durvalumab and 56.4% with chemotherapy alone in the overall analysis. The addition of olaparib also led to treatment discontinuation in 24.4% of patients vs. 20.9% in the durvalumab arm and 18.6% in the chemotherapy alone arm.

Domenica Lorusso, MD, PhD, who was not involved in the study, commented that the marginal PFS benefit of adding olaparib in DUO-E is “not surprising” because the bar set by immunotherapy is “so high in this population that it’s very difficult” to go any higher.

But the results in pMMR patients reveal “a clear additional benefit” to olaparib, said Dr. Lorusso, from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.

“The main limitation of the trial,” she continued, “is that it was not powered to make a formal comparison between the two experimental arms.”

So, what then is the added benefit of olaparib? “Unfortunately, that remains an unanswered question,” Dr. Lorusso said.

AtTEnd was sponsored by the Mario Negri Institute for Pharmacological Research.

DUO-E was funded by AstraZeneca.

Dr. Colombo declares relationships with AstraZeneca, Clovis Oncology, Esai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Roche, and Novocure.

Dr. Tan declares relationships with AstraZeneca, Karyopharm Therapeutics, Bayer, Roche, MSD, Genmab, Esai, PMV, BioNTech, Ellipses Pharma, Boehringer Ingelheim, Merck Serono, Takeda, and Clovis.

Dr. Westin declares relationships with AstraZeneca, Avenge Bio, Bayer, Bio-Path, Clovis, Genentech/Roche, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, and Zentalis; and consulting and advisory roles for AstraZeneca, Caris, Clovis, Eisai, EQRx, Genentech/Roche, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mersana, Mereo, NGM Bio, Nuvectis, Seagen, Verastem, Vincerx, Zentalis, and ZielBio.

Dr. Lorusso declares relationships with PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis, Tesaro/GSK, Genmab, Immunogen, and Roche.

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

MADRID – Research presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2023 underline the benefit of adding immunotherapy to chemotherapy in advanced or recurrent endometrial cancer, and question whether adding the PARP inhibitor olaparib to the chemo-immunotherapy combination could provide further benefit.

In the AtTEnd trial, presented on Oct. 21, more than 550 patients with advanced newly diagnosed or recurrent disease were randomized to the antiprogrammed death–ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) or placebo plus chemotherapy followed by maintenance atezolizumab or placebo.

Adding immunotherapy to chemotherapy improved progression-free survival (PFS) among all-comers – 28.1% vs. 17% at 2 years. The PFS benefit was much more pronounced among patients with mismatch repair-deficient (dMMR) disease – 50.4% vs. 16% at 2 years. Mismatch repair-deficient disease patients receiving atezolizumab also demonstrated an early overall survival benefit, according to findings from the interim analysis.

In the DUO-E trial, presented during the same Oct. 21 session, nearly 720 patients with newly diagnosed advanced or recurrent endometrial cancer were randomized to one of three groups: Chemotherapy alone with maintenance placebo, chemotherapy plus durvalumab (Imfinzi) with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab and the PARP inhibitor olaparib.

The results, published simultaneously in the Journal of Clinical Oncology, showed that adding durvalumab to chemotherapy followed by maintenance durvalumab with or without olaparib led to a significant improvement in PFS, compared with chemotherapy alone. As in the AtTEnd trial, this PFS was also more pronounced in dMMR patients.

Overall, Andrés Cervantes, MD, PhD, from the University of Valencia, Spain, and president of ESMO, explained that this research marks “very positive data for women with gynecological cancers,” with immunotherapy now incorporated into the standard of care.

However, an expert questioned whether the DUO-E trial clearly demonstrated the benefit of adding olaparib to immuno- and chemotherapy and whether certain subsets of patients may be more likely to benefit from the PARP inhibitor.
 

Inside AtTEnd

A growing body of research has shown that single agent immunotherapy is effective in treating endometrial cancer, particularly in tumors with dMMR, and that immunotherapy and chemotherapy may have a synergistic effect.

David S. P. Tan, MD, PhD, National University Cancer Institute, Singapore, who was not involved in the studies, commented that “the molecular classification of endometrial cancer is now leading us to areas that we didn’t think before [were] possible.”

The rationale for combining immunotherapy with chemotherapy, Dr. Tan explained, is that “the cytotoxicity you get from chemotherapy is partly dependent on immune activity within the tumor, and so it makes sense” to combine them.

This approach was borne out by recent positive PFS results from the NRG-GY018 trial of pembrolizumab plus chemotherapy in advanced endometrial cancer as well as from the RUBY trial of dostarlimab in primary advanced or recurrent disease.

To further investigate this chemo-immunotherapy strategy, the AtTEnd team enrolled patients with newly diagnosed or recurrent stage III-IV disease who had received no prior systemic chemotherapy for recurrence within the previous 6 months.

Overall, 551 patients from 89 sites across 10 countries were randomized to standard first-line chemotherapy – carboplatin plus paclitaxel – with either atezolizumab or placebo, followed by maintenance atezolizumab or placebo, which continued until confirmed disease progression.

The median age in the intention-to-treat population was 64-67 years. Nearly 23% of patients had dMMR tumors, and 67.2% had recurrent disease.

The baseline characteristics were well balanced and distributed between arms in the dMMR and all-comers population, said Nicoletta Colombo, MD, University of Milan–Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Italy, who presented the findings at ESMO.

Over a median follow up of 26.2 months, Dr. Colombo and colleagues observed a statistically significant improvement in PFS in the dMMR arm in favor of atezolizumab (hazard ratio, 0.36; P = .0005). At 2 years, 50.4% of patients receiving the immunotherapy were progression-free, compared with 16.0% in the placebo arm.

In all-comers, the PFS improvement with atezolizumab was less pronounced but remained significant (HR, 0.74; P = .0219).

A secondary analysis revealed, among dMMR patients, atezolizumab was associated with an overall survival advantage over placebo (HR, 0.41), with 75% of patients still alive at 2 years vs. 54.2% in the placebo arm. Dr. Colombo also noted a “clear trend” for improved overall survival with atezolizumab as well (HR, 0.82; P = .0483), but no PFS or overall survival benefit was seen with atezolizumab in MMR proficient (pMMR) patients.

Dr. Colombo said the safety profile of atezolizumab plus chemotherapy was “manageable,” with no differences in the rates of “major side effects,” although there was an increase in the rate of treatment-related grade ≥ 3 adverse events in the atezolizumab group (25.8% vs. 14.1%).

Dr. Tan noted that the AtTEnd trial revealed comparable results to earlier trials in this space but underlined that the survival curves in the interim analysis revealed a “red zone” of dMMR patients who do not respond to the combination and in whom immunotherapy is “not sufficient.”

Alongside this, Dr. Tan flagged a “blue zone” of dMMR patients who plateaued in both PFS and overall survival after 2 years. The question for these patients at this point is whether they need to continue immunotherapy beyond 24 months, he said.

But overall, Dr. Tan noted, the AtTEnd data “continue to validate practice-changing therapy for dMMR endometrial cancer patients” with immunotherapy plus chemotherapy, with the lack of benefit in pMMR disease underscoring an “unmet medical need.”
 

Inside DUO-E

The burning question, however, was whether adding a PARP inhibitor to immunotherapy and chemotherapy would boost the survival outcomes further.

The DUO-E trial involved patients with newly diagnosed stage III/IV or recurrent endometrial cancer who had not received systematic therapy for advanced disease and were naive to both PARP inhibitors and immune-mediated therapy.

Overall, 718 patients were randomized to one of three arms: Chemotherapy alone followed by maintenance placebo, chemotherapy plus durvalumab with maintenance durvalumab, or chemotherapy plus durvalumab with maintenance durvalumab plus olaparib.

Maintenance was continued until disease progression or unacceptable toxicity, or the patients met another discontinuation criteria.

About half of patients were newly diagnosed, half had recurrent disease, and approximately one-fifth had dMMR disease, said Shannon Westin, MD, from the University of Texas MD Anderson Cancer Center, Houston, who presented the findings.

Compared with placebo plus chemotherapy, patients in both the durvalumab alone and durvalumab plus olaparib arms experienced a significant improvement in PFS (HR, 0.71; P = .003; and HR, 0.55; P < .0001, respectively).

This effect was amplified in dMMR patients with durvalumab (HR, 0.42) as well as with durvalumab plus olaparib (HR, 0.41).

In pMMR patients, PFS benefit was stronger in the durvalumab-olaparib arm vs. durvalumab (HR, 0.57 vs. 0.77).

Although the overall survival analysis remains exploratory, Dr. Westin noted a trend toward better overall survival in the two treatment arms vs. placebo (HR, 0.77 with durvalumab, and HR, 0.59 with durvalumab plus olaparib).

However, adding olaparib to the equation increased the rate of grade ≥ 3 adverse events – 67.2% vs. 54.9% with durvalumab and 56.4% with chemotherapy alone in the overall analysis. The addition of olaparib also led to treatment discontinuation in 24.4% of patients vs. 20.9% in the durvalumab arm and 18.6% in the chemotherapy alone arm.

Domenica Lorusso, MD, PhD, who was not involved in the study, commented that the marginal PFS benefit of adding olaparib in DUO-E is “not surprising” because the bar set by immunotherapy is “so high in this population that it’s very difficult” to go any higher.

But the results in pMMR patients reveal “a clear additional benefit” to olaparib, said Dr. Lorusso, from Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.

“The main limitation of the trial,” she continued, “is that it was not powered to make a formal comparison between the two experimental arms.”

So, what then is the added benefit of olaparib? “Unfortunately, that remains an unanswered question,” Dr. Lorusso said.

AtTEnd was sponsored by the Mario Negri Institute for Pharmacological Research.

DUO-E was funded by AstraZeneca.

Dr. Colombo declares relationships with AstraZeneca, Clovis Oncology, Esai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Roche, and Novocure.

Dr. Tan declares relationships with AstraZeneca, Karyopharm Therapeutics, Bayer, Roche, MSD, Genmab, Esai, PMV, BioNTech, Ellipses Pharma, Boehringer Ingelheim, Merck Serono, Takeda, and Clovis.

Dr. Westin declares relationships with AstraZeneca, Avenge Bio, Bayer, Bio-Path, Clovis, Genentech/Roche, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, and Zentalis; and consulting and advisory roles for AstraZeneca, Caris, Clovis, Eisai, EQRx, Genentech/Roche, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mersana, Mereo, NGM Bio, Nuvectis, Seagen, Verastem, Vincerx, Zentalis, and ZielBio.

Dr. Lorusso declares relationships with PharmaMar, Merck Serono, Novartis, AstraZeneca, Clovis, Tesaro/GSK, Genmab, Immunogen, and Roche.

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

The prognosis for patients with advanced heart failure (HF) who fail guideline-directed medical therapy is poor, but contemporary durable left ventricular assist device (dLVAD) therapy can improve survival and quality of life for these patients. However, it remains underutilized.

Those are the key takeaways from a scientific statement on durable mechanical circulatory support, published online in the Journal of the American College of Cardiology.

“I think it is important to highlight this issue because of the sheer impact that heart failure has on American citizens,” corresponding author Jennifer Cowger, MD, MS, advanced heart failure specialist, Henry Ford Health, Detroit, said in an interview.

“End-stage heart failure has no medication that has shown a gain in survival, and most are dead by 1 year,” she said.

This scientific statement highlights the “amazing evolution of LVAD support and associated improvement in outcomes,” Dr. Cowger said.

Yet because LVADs are only implanted at roughly 170 U.S. centers, “many cardiologists are not aware of the amazing survival improvement with modern LVAD technology, and patients are under-referred,” Dr. Cowger noted.
 

Contemporary outcomes on par with heart transplant

The authors note that survival with durable LVAD (dLVAD) has markedly improved over the years. Current survival is approximately 87% at 1 year for patients supported with a contemporary LVAD.

Average patient survival is now similar to that of heart transplantation at 2 years, with 5-year dLVAD survival now approaching 60%, they point out. 

Contemporary dLVAD yields significant and sustained improvements in functional capacity. Data show that roughly 80% of patients improve to NYHA functional class I and II, with significant improvements in 6-minute walk distances and health-related quality of life, the authors note.

In addition, innovations in dLVAD technology have reduced the risk of several adverse events, including pump thrombosis, stroke, and bleeding.

“Novel devices are on the horizon of clinical investigation, offering smaller size, permitting less invasive surgical implantation, and eliminating the percutaneous lead for power supply,” the authors note.

“Unfortunately, greater adoption of dLVAD therapy has not been realized due to delayed referral of patients to advanced HF centers, insufficient clinician knowledge of contemporary dLVAD outcomes (including gains in quality of life), and deprioritization of patients with dLVAD support waiting for heart transplantation,” they write. 

In addition to highlighting contemporary outcomes with dLVAD support, the 18-page statement also includes sections on:

• Current indications and timing of referral
• Surgical considerations (device selection, surgical techniques and approach to concomitant valvular disease, and management of acute right ventricular dysfunction)
• Unique patient populations (women, children, and adult congenital heart disease)
• Summary, gaps, and future directions

A recent workshop held by the National Heart, Lung, and Blood Institute (NHLBI) identified critical gaps in the field of advanced HF.

One of the major gaps identified was the need to improve mechanical circulatory support use as a “complement or alternative” therapy to heart transplantation. The workshop also emphasized the need to “synergize” LVAD and heart transplant in the same patient to maximize health-related quality of life and survival benefit.

The NHLBI workshop also highlighted the need to model how different patient subset characteristics may affect mechanical circulatory support outcomes to inform bridge-to-transplantation or bridge-to-decision/candidacy opportunities more appropriately.

This research had no commercial funding. A number of study authors disclosed relationships with industry. The full list is available with the original article.

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

The prognosis for patients with advanced heart failure (HF) who fail guideline-directed medical therapy is poor, but contemporary durable left ventricular assist device (dLVAD) therapy can improve survival and quality of life for these patients. However, it remains underutilized.

Those are the key takeaways from a scientific statement on durable mechanical circulatory support, published online in the Journal of the American College of Cardiology.

“I think it is important to highlight this issue because of the sheer impact that heart failure has on American citizens,” corresponding author Jennifer Cowger, MD, MS, advanced heart failure specialist, Henry Ford Health, Detroit, said in an interview.

“End-stage heart failure has no medication that has shown a gain in survival, and most are dead by 1 year,” she said.

This scientific statement highlights the “amazing evolution of LVAD support and associated improvement in outcomes,” Dr. Cowger said.

Yet because LVADs are only implanted at roughly 170 U.S. centers, “many cardiologists are not aware of the amazing survival improvement with modern LVAD technology, and patients are under-referred,” Dr. Cowger noted.
 

Contemporary outcomes on par with heart transplant

The authors note that survival with durable LVAD (dLVAD) has markedly improved over the years. Current survival is approximately 87% at 1 year for patients supported with a contemporary LVAD.

Average patient survival is now similar to that of heart transplantation at 2 years, with 5-year dLVAD survival now approaching 60%, they point out. 

Contemporary dLVAD yields significant and sustained improvements in functional capacity. Data show that roughly 80% of patients improve to NYHA functional class I and II, with significant improvements in 6-minute walk distances and health-related quality of life, the authors note.

In addition, innovations in dLVAD technology have reduced the risk of several adverse events, including pump thrombosis, stroke, and bleeding.

“Novel devices are on the horizon of clinical investigation, offering smaller size, permitting less invasive surgical implantation, and eliminating the percutaneous lead for power supply,” the authors note.

“Unfortunately, greater adoption of dLVAD therapy has not been realized due to delayed referral of patients to advanced HF centers, insufficient clinician knowledge of contemporary dLVAD outcomes (including gains in quality of life), and deprioritization of patients with dLVAD support waiting for heart transplantation,” they write. 

In addition to highlighting contemporary outcomes with dLVAD support, the 18-page statement also includes sections on:

• Current indications and timing of referral
• Surgical considerations (device selection, surgical techniques and approach to concomitant valvular disease, and management of acute right ventricular dysfunction)
• Unique patient populations (women, children, and adult congenital heart disease)
• Summary, gaps, and future directions

A recent workshop held by the National Heart, Lung, and Blood Institute (NHLBI) identified critical gaps in the field of advanced HF.

One of the major gaps identified was the need to improve mechanical circulatory support use as a “complement or alternative” therapy to heart transplantation. The workshop also emphasized the need to “synergize” LVAD and heart transplant in the same patient to maximize health-related quality of life and survival benefit.

The NHLBI workshop also highlighted the need to model how different patient subset characteristics may affect mechanical circulatory support outcomes to inform bridge-to-transplantation or bridge-to-decision/candidacy opportunities more appropriately.

This research had no commercial funding. A number of study authors disclosed relationships with industry. The full list is available with the original article.

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

The prognosis for patients with advanced heart failure (HF) who fail guideline-directed medical therapy is poor, but contemporary durable left ventricular assist device (dLVAD) therapy can improve survival and quality of life for these patients. However, it remains underutilized.

Those are the key takeaways from a scientific statement on durable mechanical circulatory support, published online in the Journal of the American College of Cardiology.

“I think it is important to highlight this issue because of the sheer impact that heart failure has on American citizens,” corresponding author Jennifer Cowger, MD, MS, advanced heart failure specialist, Henry Ford Health, Detroit, said in an interview.

“End-stage heart failure has no medication that has shown a gain in survival, and most are dead by 1 year,” she said.

This scientific statement highlights the “amazing evolution of LVAD support and associated improvement in outcomes,” Dr. Cowger said.

Yet because LVADs are only implanted at roughly 170 U.S. centers, “many cardiologists are not aware of the amazing survival improvement with modern LVAD technology, and patients are under-referred,” Dr. Cowger noted.
 

Contemporary outcomes on par with heart transplant

The authors note that survival with durable LVAD (dLVAD) has markedly improved over the years. Current survival is approximately 87% at 1 year for patients supported with a contemporary LVAD.

Average patient survival is now similar to that of heart transplantation at 2 years, with 5-year dLVAD survival now approaching 60%, they point out. 

Contemporary dLVAD yields significant and sustained improvements in functional capacity. Data show that roughly 80% of patients improve to NYHA functional class I and II, with significant improvements in 6-minute walk distances and health-related quality of life, the authors note.

In addition, innovations in dLVAD technology have reduced the risk of several adverse events, including pump thrombosis, stroke, and bleeding.

“Novel devices are on the horizon of clinical investigation, offering smaller size, permitting less invasive surgical implantation, and eliminating the percutaneous lead for power supply,” the authors note.

“Unfortunately, greater adoption of dLVAD therapy has not been realized due to delayed referral of patients to advanced HF centers, insufficient clinician knowledge of contemporary dLVAD outcomes (including gains in quality of life), and deprioritization of patients with dLVAD support waiting for heart transplantation,” they write. 

In addition to highlighting contemporary outcomes with dLVAD support, the 18-page statement also includes sections on:

• Current indications and timing of referral
• Surgical considerations (device selection, surgical techniques and approach to concomitant valvular disease, and management of acute right ventricular dysfunction)
• Unique patient populations (women, children, and adult congenital heart disease)
• Summary, gaps, and future directions

A recent workshop held by the National Heart, Lung, and Blood Institute (NHLBI) identified critical gaps in the field of advanced HF.

One of the major gaps identified was the need to improve mechanical circulatory support use as a “complement or alternative” therapy to heart transplantation. The workshop also emphasized the need to “synergize” LVAD and heart transplant in the same patient to maximize health-related quality of life and survival benefit.

The NHLBI workshop also highlighted the need to model how different patient subset characteristics may affect mechanical circulatory support outcomes to inform bridge-to-transplantation or bridge-to-decision/candidacy opportunities more appropriately.

This research had no commercial funding. A number of study authors disclosed relationships with industry. The full list is available with the original article.

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

TOPLINE:

When provided detailed information on options, most men with low-risk prostate cancer chose active surveillance over treatment, and there was no difference in outcomes, new research from Italy shows.

METHODOLOGY:

• Active surveillance for patients with low-risk prostate cancer has been recommended for years, but its adoption often varies within and between countries.
• The current study, based in Italy, aimed to promote the adoption of active surveillance in two regions in Northern Italy and to understand patient acceptance and outcomes in comparison with active treatment.
• Men newly diagnosed with low-risk prostate cancer between June 2015 and December 2021 were eligible. All were informed of treatment options and were offered active surveillance.
• Multilevel models identified factors associated with choosing active surveillance over active treatment, which consisted of either radical prostatectomy or radiation therapy.

TAKEAWAY:

• Overall, 83% (706 of 852) men chose active surveillance over immediate treatment. There was an upward trend over time, from 78% in 2015-2017 to 90% in 2020-2021.
• Patients who chose active surveillance over any radical treatment were more likely to be aged 75 years or older (odds ratio, 4.27), to have a Charlson Comorbidity Index ≥ 2 (OR, 1.98), to have undergone independent revision of the first biopsy (OR, 2.35), and to have undergone multidisciplinary assessment (OR, 2.65).
• Worse prostate cancer prognostic factors, such as stage T2a (OR, 0.54) and Gleason Score 3+4 (OR, 0.20), were associated with lower odds of choosing active surveillance than any radical treatment.
• In an adjusted intention-to-treat analysis, among patients who initially chose active surveillance, overall survival was not worse in comparison with those who chose any radical treatment (hazard ratio, 0.86; 95% confidence interval, 0.41-1.79) or in comparison with those who chose radical prostatectomy (HR, 0.90; 95% CI, 0.37-2.20).

IN PRACTICE:

“The main remarkable finding of [the trial] is represented by the widespread adoption of active surveillance in our [Regional Oncology Network] since the beginning of the study, and the increasing trend over time, reaching approximately 90% of eligible patients in 2020 to 2021,” the authors wrote.

SOURCE:

The study, with first author Giovannino Ciccone, MD, PhD, AOU City of Health and Science of Turin, Italy, was published online in JAMA Network Open.

LIMITATIONS:

Key limitations include the relatively short follow-up (median, 57 months), variability between centers in terms of enrolling patients and discussing their choices, and the high rate of patients who abandoned active surveillance by year 2 of follow-up. Overall, about 281 patients (~40%) abandoned active surveillance by year 2, most commonly because of biochemical progression.

DISCLOSURES:

The START project was funded by the Fondazione Compagnia di San Paolo and partially by Rete Oncologica del Piemonte e Valle d’Aosta, Turin, Italy. Dr. Ciccone has disclosed no relevant financial relationships.

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

TOPLINE:

When provided detailed information on options, most men with low-risk prostate cancer chose active surveillance over treatment, and there was no difference in outcomes, new research from Italy shows.

METHODOLOGY:

• Active surveillance for patients with low-risk prostate cancer has been recommended for years, but its adoption often varies within and between countries.
• The current study, based in Italy, aimed to promote the adoption of active surveillance in two regions in Northern Italy and to understand patient acceptance and outcomes in comparison with active treatment.
• Men newly diagnosed with low-risk prostate cancer between June 2015 and December 2021 were eligible. All were informed of treatment options and were offered active surveillance.
• Multilevel models identified factors associated with choosing active surveillance over active treatment, which consisted of either radical prostatectomy or radiation therapy.

TAKEAWAY:

• Overall, 83% (706 of 852) men chose active surveillance over immediate treatment. There was an upward trend over time, from 78% in 2015-2017 to 90% in 2020-2021.
• Patients who chose active surveillance over any radical treatment were more likely to be aged 75 years or older (odds ratio, 4.27), to have a Charlson Comorbidity Index ≥ 2 (OR, 1.98), to have undergone independent revision of the first biopsy (OR, 2.35), and to have undergone multidisciplinary assessment (OR, 2.65).
• Worse prostate cancer prognostic factors, such as stage T2a (OR, 0.54) and Gleason Score 3+4 (OR, 0.20), were associated with lower odds of choosing active surveillance than any radical treatment.
• In an adjusted intention-to-treat analysis, among patients who initially chose active surveillance, overall survival was not worse in comparison with those who chose any radical treatment (hazard ratio, 0.86; 95% confidence interval, 0.41-1.79) or in comparison with those who chose radical prostatectomy (HR, 0.90; 95% CI, 0.37-2.20).

IN PRACTICE:

“The main remarkable finding of [the trial] is represented by the widespread adoption of active surveillance in our [Regional Oncology Network] since the beginning of the study, and the increasing trend over time, reaching approximately 90% of eligible patients in 2020 to 2021,” the authors wrote.

SOURCE:

The study, with first author Giovannino Ciccone, MD, PhD, AOU City of Health and Science of Turin, Italy, was published online in JAMA Network Open.

LIMITATIONS:

Key limitations include the relatively short follow-up (median, 57 months), variability between centers in terms of enrolling patients and discussing their choices, and the high rate of patients who abandoned active surveillance by year 2 of follow-up. Overall, about 281 patients (~40%) abandoned active surveillance by year 2, most commonly because of biochemical progression.

DISCLOSURES:

The START project was funded by the Fondazione Compagnia di San Paolo and partially by Rete Oncologica del Piemonte e Valle d’Aosta, Turin, Italy. Dr. Ciccone has disclosed no relevant financial relationships.

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

TOPLINE:

When provided detailed information on options, most men with low-risk prostate cancer chose active surveillance over treatment, and there was no difference in outcomes, new research from Italy shows.

METHODOLOGY:

• Active surveillance for patients with low-risk prostate cancer has been recommended for years, but its adoption often varies within and between countries.
• The current study, based in Italy, aimed to promote the adoption of active surveillance in two regions in Northern Italy and to understand patient acceptance and outcomes in comparison with active treatment.
• Men newly diagnosed with low-risk prostate cancer between June 2015 and December 2021 were eligible. All were informed of treatment options and were offered active surveillance.
• Multilevel models identified factors associated with choosing active surveillance over active treatment, which consisted of either radical prostatectomy or radiation therapy.

TAKEAWAY:

• Overall, 83% (706 of 852) men chose active surveillance over immediate treatment. There was an upward trend over time, from 78% in 2015-2017 to 90% in 2020-2021.
• Patients who chose active surveillance over any radical treatment were more likely to be aged 75 years or older (odds ratio, 4.27), to have a Charlson Comorbidity Index ≥ 2 (OR, 1.98), to have undergone independent revision of the first biopsy (OR, 2.35), and to have undergone multidisciplinary assessment (OR, 2.65).
• Worse prostate cancer prognostic factors, such as stage T2a (OR, 0.54) and Gleason Score 3+4 (OR, 0.20), were associated with lower odds of choosing active surveillance than any radical treatment.
• In an adjusted intention-to-treat analysis, among patients who initially chose active surveillance, overall survival was not worse in comparison with those who chose any radical treatment (hazard ratio, 0.86; 95% confidence interval, 0.41-1.79) or in comparison with those who chose radical prostatectomy (HR, 0.90; 95% CI, 0.37-2.20).

IN PRACTICE:

“The main remarkable finding of [the trial] is represented by the widespread adoption of active surveillance in our [Regional Oncology Network] since the beginning of the study, and the increasing trend over time, reaching approximately 90% of eligible patients in 2020 to 2021,” the authors wrote.

SOURCE:

The study, with first author Giovannino Ciccone, MD, PhD, AOU City of Health and Science of Turin, Italy, was published online in JAMA Network Open.

LIMITATIONS:

Key limitations include the relatively short follow-up (median, 57 months), variability between centers in terms of enrolling patients and discussing their choices, and the high rate of patients who abandoned active surveillance by year 2 of follow-up. Overall, about 281 patients (~40%) abandoned active surveillance by year 2, most commonly because of biochemical progression.

DISCLOSURES:

The START project was funded by the Fondazione Compagnia di San Paolo and partially by Rete Oncologica del Piemonte e Valle d’Aosta, Turin, Italy. Dr. Ciccone has disclosed no relevant financial relationships.

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

DALLAS – Researchers identified behavioral, psychological, and environmental predictors of continued weight loss maintenance vs. weight regain in a large cohort of members of WeightWatchers who had successful long-term weight loss.

On average, the participants had lost 25.5 kg (56 lb) and kept it off for 3.5 years, when they entered the 1-year study.

At study entry and 1 year later, the participants replied to several questionnaires that asked about predictors of weight loss maintenance.

Compared with people who gained weight over the 1-year study, those who maintained their weight within 2.3 kg (5 lb) reported more consistent monitoring of their diet and weight and greater acceptance of uncomfortable food cravings.

They also had reduced disinhibition (tendency to overeat) when faced with food cues, as well as less pain and a more positive body image “at any weight, shape, or size,” Suzanne Phelan, MD, PhD, reported.

Dr. Phelan, from the department of kinesiology and public health, California Polytechnic State University, San Luis Obispo, presented the study in an Obesity symposium at the annual meeting of the Obesity Society, and it was simultaneously published in the journal. The study was selected as one of five top papers submitted to the journal to coincide with the meeting.

Future interventions to prevent weight regain should target overeating in response to internal and external food cues and declines in self-monitoring and body image, Dr. Phelan said.

The study aimed to identify behaviors that might predict who might “beat the odds” and sustain long-term weight loss, she said in an interview.

The findings suggest that the people who maintained their weight loss had developed skills to help them cope with cravings and not respond by eating, she said. Continued self-monitoring and body acceptance and appreciation (all body sizes are beautiful) were key elements of successful weight-loss maintenance.
 

No antiobesity drugs or surgery; don’t forget behavioral stuff

Importantly, although 43% of the study participants regained more than five pounds during this 1-year study, they still remained at 18% below their starting weight, “indicating that they were largely successful at weight loss,” Dr. Phelan said.

Michael D. Jensen, MD, editor-in-chief of Obesity, echoed this.

The researchers “did find some weak predictors of success,” said Dr. Jensen, from Mayo Clinic, Rochester, Minn. “But perhaps as important,” he said, “was that at the end of the trial, even those who had regained some slight weight still had 18% weight loss – which is not trivial – after, on average, 4.5 years with a standard commercial weight management program.

“At every talk I go to here,” the message is, “Let’s stampede towards use of the drugs and skip diet and exercise and behavioral stuff,” he observed. “I would argue,” he said, “that when it works, it works really well, and it’s free. So this idea that we shouldn’t even try it, because we know it’s going to fail, is wrong.

“If you have the right group, they have a decent chance of having a sufficiently good response that you don’t have to give the medications and you don’t have to send them for bariatric surgery.

“Once you learn from these programs what to do, you’re not paying $1,000 a month for a drug and you haven’t had bariatric surgery,” Dr. Jensen noted. “Their 3 years of follow-up of WeightWatchers cost less than 1 month worth of one of these [antiobesity medications].”

The predictive findings were like ‘”icing on the cake,” he said. Anybody can find five people who’ve done well with therapy, but this study was in more than 2,800 people who did well with a commercial program that is not expensive.
 

Study design and findings

Between 2019 and 2020, WeightWatchers invited adult members who had maintained weight loss of at least 9.1 kg (20 lb) for at least 1 year to participate in this study.

Of 7,025 participants who entered the study, 4,004 individuals (57%) who did not complete the 1-year questionnaires and others with implausible weight were excluded, leaving a final sample of 2,843 participants.

Most participants were women (92%), non-Hispanic White (95%), married (92%), and college educated. They had a mean age of 56 years.

On average, the participants had a body mass index (BMI) of 35.9 kg/m² (grade 2 obesity) at the start of the WeightWatchers program and a BMI of 26.7 when they entered the current study.

At the 1-year follow-up, 57% of the participants had maintained the same weight (within 2.3 kg) as when they enrolled in the study, and 43% had gained ≥ 2.3 kg.

On average, the weight-loss maintainers had gained 0.4 kg (0.88 lb). The weight gainers had gained 7.2 kg (15.9 lb) but were still 19.1 kg (42.1 lb) below the weight they had when they started the WeightWatchers program.

At baseline, compared with the weight gainers, the weight-loss maintainers were on average older (58 vs. 52 years), had a lower initial BMI (26 vs. 28), and had longer duration of weight loss maintenance (4 vs. 3 years).

At 1 year, those who had maintained their weight loss had greater self-monitoring, psychological coping, physical activity strategies, dietary choice strategies, and eating and physical activity habits, and they had less eating initiation in the absence of hunger.

They also had less disinhibition, more willingness to ignore cravings and accept food urges, more future orientation, more mindfulness, more positive body image and body satisfaction, better general health and mental health, and less bodily pain.

This research was supported by a grant to Dr. Phelan from WeightWatchers (WW) International, and three study authors are employees and shareholders of the company. Dr. Jensen discloses consulting for Biohaven Pharmaceuticals and for Seattle Gummy Co.

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

DALLAS – Researchers identified behavioral, psychological, and environmental predictors of continued weight loss maintenance vs. weight regain in a large cohort of members of WeightWatchers who had successful long-term weight loss.

On average, the participants had lost 25.5 kg (56 lb) and kept it off for 3.5 years, when they entered the 1-year study.

At study entry and 1 year later, the participants replied to several questionnaires that asked about predictors of weight loss maintenance.

Compared with people who gained weight over the 1-year study, those who maintained their weight within 2.3 kg (5 lb) reported more consistent monitoring of their diet and weight and greater acceptance of uncomfortable food cravings.

They also had reduced disinhibition (tendency to overeat) when faced with food cues, as well as less pain and a more positive body image “at any weight, shape, or size,” Suzanne Phelan, MD, PhD, reported.

Dr. Phelan, from the department of kinesiology and public health, California Polytechnic State University, San Luis Obispo, presented the study in an Obesity symposium at the annual meeting of the Obesity Society, and it was simultaneously published in the journal. The study was selected as one of five top papers submitted to the journal to coincide with the meeting.

Future interventions to prevent weight regain should target overeating in response to internal and external food cues and declines in self-monitoring and body image, Dr. Phelan said.

The study aimed to identify behaviors that might predict who might “beat the odds” and sustain long-term weight loss, she said in an interview.

The findings suggest that the people who maintained their weight loss had developed skills to help them cope with cravings and not respond by eating, she said. Continued self-monitoring and body acceptance and appreciation (all body sizes are beautiful) were key elements of successful weight-loss maintenance.
 

No antiobesity drugs or surgery; don’t forget behavioral stuff

Importantly, although 43% of the study participants regained more than five pounds during this 1-year study, they still remained at 18% below their starting weight, “indicating that they were largely successful at weight loss,” Dr. Phelan said.

Michael D. Jensen, MD, editor-in-chief of Obesity, echoed this.

The researchers “did find some weak predictors of success,” said Dr. Jensen, from Mayo Clinic, Rochester, Minn. “But perhaps as important,” he said, “was that at the end of the trial, even those who had regained some slight weight still had 18% weight loss – which is not trivial – after, on average, 4.5 years with a standard commercial weight management program.

“At every talk I go to here,” the message is, “Let’s stampede towards use of the drugs and skip diet and exercise and behavioral stuff,” he observed. “I would argue,” he said, “that when it works, it works really well, and it’s free. So this idea that we shouldn’t even try it, because we know it’s going to fail, is wrong.

“If you have the right group, they have a decent chance of having a sufficiently good response that you don’t have to give the medications and you don’t have to send them for bariatric surgery.

“Once you learn from these programs what to do, you’re not paying $1,000 a month for a drug and you haven’t had bariatric surgery,” Dr. Jensen noted. “Their 3 years of follow-up of WeightWatchers cost less than 1 month worth of one of these [antiobesity medications].”

The predictive findings were like ‘”icing on the cake,” he said. Anybody can find five people who’ve done well with therapy, but this study was in more than 2,800 people who did well with a commercial program that is not expensive.
 

Study design and findings

Between 2019 and 2020, WeightWatchers invited adult members who had maintained weight loss of at least 9.1 kg (20 lb) for at least 1 year to participate in this study.

Of 7,025 participants who entered the study, 4,004 individuals (57%) who did not complete the 1-year questionnaires and others with implausible weight were excluded, leaving a final sample of 2,843 participants.

Most participants were women (92%), non-Hispanic White (95%), married (92%), and college educated. They had a mean age of 56 years.

On average, the participants had a body mass index (BMI) of 35.9 kg/m² (grade 2 obesity) at the start of the WeightWatchers program and a BMI of 26.7 when they entered the current study.

At the 1-year follow-up, 57% of the participants had maintained the same weight (within 2.3 kg) as when they enrolled in the study, and 43% had gained ≥ 2.3 kg.

On average, the weight-loss maintainers had gained 0.4 kg (0.88 lb). The weight gainers had gained 7.2 kg (15.9 lb) but were still 19.1 kg (42.1 lb) below the weight they had when they started the WeightWatchers program.

At baseline, compared with the weight gainers, the weight-loss maintainers were on average older (58 vs. 52 years), had a lower initial BMI (26 vs. 28), and had longer duration of weight loss maintenance (4 vs. 3 years).

At 1 year, those who had maintained their weight loss had greater self-monitoring, psychological coping, physical activity strategies, dietary choice strategies, and eating and physical activity habits, and they had less eating initiation in the absence of hunger.

They also had less disinhibition, more willingness to ignore cravings and accept food urges, more future orientation, more mindfulness, more positive body image and body satisfaction, better general health and mental health, and less bodily pain.

This research was supported by a grant to Dr. Phelan from WeightWatchers (WW) International, and three study authors are employees and shareholders of the company. Dr. Jensen discloses consulting for Biohaven Pharmaceuticals and for Seattle Gummy Co.

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

DALLAS – Researchers identified behavioral, psychological, and environmental predictors of continued weight loss maintenance vs. weight regain in a large cohort of members of WeightWatchers who had successful long-term weight loss.

On average, the participants had lost 25.5 kg (56 lb) and kept it off for 3.5 years, when they entered the 1-year study.

At study entry and 1 year later, the participants replied to several questionnaires that asked about predictors of weight loss maintenance.

Compared with people who gained weight over the 1-year study, those who maintained their weight within 2.3 kg (5 lb) reported more consistent monitoring of their diet and weight and greater acceptance of uncomfortable food cravings.

They also had reduced disinhibition (tendency to overeat) when faced with food cues, as well as less pain and a more positive body image “at any weight, shape, or size,” Suzanne Phelan, MD, PhD, reported.

Dr. Phelan, from the department of kinesiology and public health, California Polytechnic State University, San Luis Obispo, presented the study in an Obesity symposium at the annual meeting of the Obesity Society, and it was simultaneously published in the journal. The study was selected as one of five top papers submitted to the journal to coincide with the meeting.

Future interventions to prevent weight regain should target overeating in response to internal and external food cues and declines in self-monitoring and body image, Dr. Phelan said.

The study aimed to identify behaviors that might predict who might “beat the odds” and sustain long-term weight loss, she said in an interview.

The findings suggest that the people who maintained their weight loss had developed skills to help them cope with cravings and not respond by eating, she said. Continued self-monitoring and body acceptance and appreciation (all body sizes are beautiful) were key elements of successful weight-loss maintenance.
 

No antiobesity drugs or surgery; don’t forget behavioral stuff

Importantly, although 43% of the study participants regained more than five pounds during this 1-year study, they still remained at 18% below their starting weight, “indicating that they were largely successful at weight loss,” Dr. Phelan said.

Michael D. Jensen, MD, editor-in-chief of Obesity, echoed this.

The researchers “did find some weak predictors of success,” said Dr. Jensen, from Mayo Clinic, Rochester, Minn. “But perhaps as important,” he said, “was that at the end of the trial, even those who had regained some slight weight still had 18% weight loss – which is not trivial – after, on average, 4.5 years with a standard commercial weight management program.

“At every talk I go to here,” the message is, “Let’s stampede towards use of the drugs and skip diet and exercise and behavioral stuff,” he observed. “I would argue,” he said, “that when it works, it works really well, and it’s free. So this idea that we shouldn’t even try it, because we know it’s going to fail, is wrong.

“If you have the right group, they have a decent chance of having a sufficiently good response that you don’t have to give the medications and you don’t have to send them for bariatric surgery.

“Once you learn from these programs what to do, you’re not paying $1,000 a month for a drug and you haven’t had bariatric surgery,” Dr. Jensen noted. “Their 3 years of follow-up of WeightWatchers cost less than 1 month worth of one of these [antiobesity medications].”

The predictive findings were like ‘”icing on the cake,” he said. Anybody can find five people who’ve done well with therapy, but this study was in more than 2,800 people who did well with a commercial program that is not expensive.
 

Study design and findings

Between 2019 and 2020, WeightWatchers invited adult members who had maintained weight loss of at least 9.1 kg (20 lb) for at least 1 year to participate in this study.

Of 7,025 participants who entered the study, 4,004 individuals (57%) who did not complete the 1-year questionnaires and others with implausible weight were excluded, leaving a final sample of 2,843 participants.

Most participants were women (92%), non-Hispanic White (95%), married (92%), and college educated. They had a mean age of 56 years.

On average, the participants had a body mass index (BMI) of 35.9 kg/m² (grade 2 obesity) at the start of the WeightWatchers program and a BMI of 26.7 when they entered the current study.

At the 1-year follow-up, 57% of the participants had maintained the same weight (within 2.3 kg) as when they enrolled in the study, and 43% had gained ≥ 2.3 kg.

On average, the weight-loss maintainers had gained 0.4 kg (0.88 lb). The weight gainers had gained 7.2 kg (15.9 lb) but were still 19.1 kg (42.1 lb) below the weight they had when they started the WeightWatchers program.

At baseline, compared with the weight gainers, the weight-loss maintainers were on average older (58 vs. 52 years), had a lower initial BMI (26 vs. 28), and had longer duration of weight loss maintenance (4 vs. 3 years).

At 1 year, those who had maintained their weight loss had greater self-monitoring, psychological coping, physical activity strategies, dietary choice strategies, and eating and physical activity habits, and they had less eating initiation in the absence of hunger.

They also had less disinhibition, more willingness to ignore cravings and accept food urges, more future orientation, more mindfulness, more positive body image and body satisfaction, better general health and mental health, and less bodily pain.

This research was supported by a grant to Dr. Phelan from WeightWatchers (WW) International, and three study authors are employees and shareholders of the company. Dr. Jensen discloses consulting for Biohaven Pharmaceuticals and for Seattle Gummy Co.

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

MILAN – A tool kit combining a wearable device with automated algorithms allows for the passive monitoring of disease parameters in people with multiple sclerosis (MS) and may even be able to predict the course of the disease, suggests a pilot study.

Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.

The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.

Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Leveraging big data to improve outcomes

The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.

For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.

Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.

To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.

This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
 

Feasible with high levels of confidence

Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.

The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.

The team reports that the data from the tool kit “are in line with those reported in the literature.”

It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.

Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.

The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.

Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.

They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
 

Reducing daily step count

Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”

She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.

“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”

The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.

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

MILAN – A tool kit combining a wearable device with automated algorithms allows for the passive monitoring of disease parameters in people with multiple sclerosis (MS) and may even be able to predict the course of the disease, suggests a pilot study.

Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.

The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.

Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Leveraging big data to improve outcomes

The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.

For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.

Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.

To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.

This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
 

Feasible with high levels of confidence

Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.

The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.

The team reports that the data from the tool kit “are in line with those reported in the literature.”

It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.

Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.

The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.

Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.

They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
 

Reducing daily step count

Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”

She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.

“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”

The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.

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

MILAN – A tool kit combining a wearable device with automated algorithms allows for the passive monitoring of disease parameters in people with multiple sclerosis (MS) and may even be able to predict the course of the disease, suggests a pilot study.

Twenty patients were enrolled, only half of whom correctly completed all of the assessments and wore the included smartwatch regularly. Importantly, the data reported back for analysis was in line with expectations, and the patient feedback was positive.

The tool kit “seems feasible and usable to remotely monitor multiple domains of health status in people with multiple sclerosis,” conclude Ludovico Pedullà, PhD, Italian Multiple Sclerosis Foundation, Genoa, and colleagues.

Further analysis of the dataset, including the artificial intelligence and machine-learning algorithms, may allow the prediction of “relevant changes throughout the course of multiple sclerosis” and anticipate the need for therapeutic interventions.

The findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting.
 

Leveraging big data to improve outcomes

The authors note that the primary aim of the pan-European ALAMEDA project is to leverage “big data” through artificial intelligence and machine learning to provide “clinically actionable information” on patients with brain disorders that “complements medical recommendations” and thus improves treatment.

For the current pilot study, the researchers developed an integrated platform to collect patient-centered data from wearables and mobile devices using digital patient-reported outcomes (ePROs), with the aim of testing the resulting tool kit’s feasibility and usability in people with MS.

Dr. Pedullà said that they wanted to have “passive monitoring” of patients over the course of their daily lives and therefore searched for the best devices and the most relevant patient reported outcomes as well as used “innovative algorithms” to analyze the data to try to predict the disease course.

To reduce dropouts and increase adherence to the tool kit, they described the project to patients with MS and asked for their feedback to determine whether what they had designed was feasible from the patient perspective, Dr. Pedullà said.

This led to some changes in the way data were collected, and the team developed a social network channel so patients would be able to ask for support and stay engaged in the study.
 

Feasible with high levels of confidence

Twenty people with relapsing-remitting MS were enrolled, of whom 14 were women. The mean age was 37.8 years, and the mean disease duration was 9.1 years. The mean Expanded Disability Status Scale was 2.2.

The participants were asked to use the tool kit for 1 year, with half reaching the 6-month milestone. Participants correctly completed 53% of the scheduled ePROs and regularly wore the smartwatch without reporting discomfort.

The team reports that the data from the tool kit “are in line with those reported in the literature.”

It showed that participants took an average of 8,415 steps per day and completed 9.8 minutes of vigorous activity and 14.5 minutes of moderate activity daily. Daily sedentary minutes were 705.1.

Patients had a mean Perceived Deficit Questionnaire score of 25.2, a Beck Anxiety Inventory score of 17.3, a score on the 12-Item Multiple Sclerosis Walking Scale of 37.2, and an arm function on the Multiple Sclerosis Questionnaire of 47.4.

The mean Modified Fatigue Impact Scale score was 18.5, and the Pittsburgh Sleep Quality Index score was 25.2. The System Usability Scale revealed “high levels of confidence” with the tool kit, the team says, as well as “very high” intention of using it in the future.

Dr. Pedullà said that the researchers now want to evaluate the feasibility of the tool kit further by analyzing the adherence and usability data and targeting it to the patients who are most likely to use it.

They also want to determine not only whether the use of wearables in this way can predict relapse in multiple sclerosis but also disease progression, particularly as the current definitions are evolving.
 

Reducing daily step count

Approached for comment, Riley M. Bove, MD, MSc, Assistant Professor, UCSF Weill Institute for Neurosciences, San Francisco, said that the study is “very interesting and in line with what has been previously published.”

She pointed to a recent study that she co-authored, in which remote monitoring via a continuous step counter revealed that a decreasing average daily step count was associated with the worsening of standard ambulatory measures.

“There are nice benefits of an integrated platform” such as what was used in the current study, Dr. Bove noted, adding that it is “even better if it can also send the data to clinicians.”

The ALAMEDA project has received funding from the European Union’s Horizon 2020 research and innovation program. No relevant financial relationships declared.

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

The US Department of Veterans Affairs (VA) and 13 health care systems have signed a pledge for interoperability—to securely share data on veteran health care, regardless of whether it is provided inside the VA or not.

“This pledge will improve veteran health care by giving us seamless, immediate access to a patient’s medical history, which will help us make timely and accurate treatment decisions,” said VA Under Secretary for Health Shereef Elnahal, MD, MBA. “It will also empower VA to send helpful information to our partner health systems that they can then offer to veterans in their care—including information about new benefits we are offering under the PACT Act, no-cost emergency suicide care, and more.”

The pledge will allow the health systems to access local, state, and federal health resources and will provide the VA access to health system clinical and administrative data for quality assessment and care coordination. The pledge signers are committed to developing and providing capabilities that: (1) Accurately identify veterans when they seek care from clinicians in [the signers’] communities; (2) Connect veterans with VA and community resources that promote health and health care—especially VA services that lower veterans’ out-of-pocket expenses; and (3) Responsively and reliably coordinate care for shared patients—including exchanging care information requested and provided.

In addition to helping reduce the financial burden for veterans, the VA says, the information sharing could help clinicians outside the VA system to provide more targeted care: “[I]t will also allow us to send helpful information to our partner health systems that they can then offer to veterans in their care,” Elnahal said, “to include information about new benefits we are offering under the PACT Act and other resources that assist with suicide prevention and identifying social risk factors."

The first pledge partners are Emory Healthcare, Inova, Jefferson Health, Sanford Health, University of California Davis Health, Intermountain Health, Mass General Brigham, Rush Health, Tufts Medicine, Marshfield Clinic, Kaiser Permanente Health Plan and Hospitals, University of Pittsburg Medical Center, and Atrium Health. Any health system or clinician that supports the pledge’s objectives is encouraged to participate, the VA says. Signers have begun work, and aim to provide proof-of-concept in early 2024.

The US Department of Veterans Affairs (VA) and 13 health care systems have signed a pledge for interoperability—to securely share data on veteran health care, regardless of whether it is provided inside the VA or not.

“This pledge will improve veteran health care by giving us seamless, immediate access to a patient’s medical history, which will help us make timely and accurate treatment decisions,” said VA Under Secretary for Health Shereef Elnahal, MD, MBA. “It will also empower VA to send helpful information to our partner health systems that they can then offer to veterans in their care—including information about new benefits we are offering under the PACT Act, no-cost emergency suicide care, and more.”

The pledge will allow the health systems to access local, state, and federal health resources and will provide the VA access to health system clinical and administrative data for quality assessment and care coordination. The pledge signers are committed to developing and providing capabilities that: (1) Accurately identify veterans when they seek care from clinicians in [the signers’] communities; (2) Connect veterans with VA and community resources that promote health and health care—especially VA services that lower veterans’ out-of-pocket expenses; and (3) Responsively and reliably coordinate care for shared patients—including exchanging care information requested and provided.

In addition to helping reduce the financial burden for veterans, the VA says, the information sharing could help clinicians outside the VA system to provide more targeted care: “[I]t will also allow us to send helpful information to our partner health systems that they can then offer to veterans in their care,” Elnahal said, “to include information about new benefits we are offering under the PACT Act and other resources that assist with suicide prevention and identifying social risk factors."

The first pledge partners are Emory Healthcare, Inova, Jefferson Health, Sanford Health, University of California Davis Health, Intermountain Health, Mass General Brigham, Rush Health, Tufts Medicine, Marshfield Clinic, Kaiser Permanente Health Plan and Hospitals, University of Pittsburg Medical Center, and Atrium Health. Any health system or clinician that supports the pledge’s objectives is encouraged to participate, the VA says. Signers have begun work, and aim to provide proof-of-concept in early 2024.

The US Department of Veterans Affairs (VA) and 13 health care systems have signed a pledge for interoperability—to securely share data on veteran health care, regardless of whether it is provided inside the VA or not.

“This pledge will improve veteran health care by giving us seamless, immediate access to a patient’s medical history, which will help us make timely and accurate treatment decisions,” said VA Under Secretary for Health Shereef Elnahal, MD, MBA. “It will also empower VA to send helpful information to our partner health systems that they can then offer to veterans in their care—including information about new benefits we are offering under the PACT Act, no-cost emergency suicide care, and more.”

The pledge will allow the health systems to access local, state, and federal health resources and will provide the VA access to health system clinical and administrative data for quality assessment and care coordination. The pledge signers are committed to developing and providing capabilities that: (1) Accurately identify veterans when they seek care from clinicians in [the signers’] communities; (2) Connect veterans with VA and community resources that promote health and health care—especially VA services that lower veterans’ out-of-pocket expenses; and (3) Responsively and reliably coordinate care for shared patients—including exchanging care information requested and provided.

In addition to helping reduce the financial burden for veterans, the VA says, the information sharing could help clinicians outside the VA system to provide more targeted care: “[I]t will also allow us to send helpful information to our partner health systems that they can then offer to veterans in their care,” Elnahal said, “to include information about new benefits we are offering under the PACT Act and other resources that assist with suicide prevention and identifying social risk factors."

The first pledge partners are Emory Healthcare, Inova, Jefferson Health, Sanford Health, University of California Davis Health, Intermountain Health, Mass General Brigham, Rush Health, Tufts Medicine, Marshfield Clinic, Kaiser Permanente Health Plan and Hospitals, University of Pittsburg Medical Center, and Atrium Health. Any health system or clinician that supports the pledge’s objectives is encouraged to participate, the VA says. Signers have begun work, and aim to provide proof-of-concept in early 2024.

Key clinical point: Ultrasound assessment of individuals with painful ankles revealed that abnormalities of the flexor retinacula (FR) were more common in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA).

Major finding: The FR were thicker in patients with PsA vs patients with RA and control individuals (0.96 vs 0.64 and 0.56, respectively; both P < .001), with abnormalities, such as retinaculitis (39.0% vs 2.7%), hypoechogenicity (46.0% vs 6.8%), power Doppler positivity (43.0% vs 8.1%), and periostosis (43.0% vs 8.1%), being significantly more prevalent in patients with PsA vs RA (all P < .001).

Study details: Findings are from a cross-sectional observational study including patients with PsA (n = 23) and RA (n = 37) who reported painful ankles and control individuals (n = 20) without rheumatic disease or ankle pain.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Forien M et al. Ankle retinacula abnormalities as features of psoriatic arthritis: An ultrasound study. Joint Bone Spine. 2023 (Oct 4). doi: 10.1016/j.jbspin.2023.105649

Key clinical point: Ultrasound assessment of individuals with painful ankles revealed that abnormalities of the flexor retinacula (FR) were more common in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA).

Major finding: The FR were thicker in patients with PsA vs patients with RA and control individuals (0.96 vs 0.64 and 0.56, respectively; both P < .001), with abnormalities, such as retinaculitis (39.0% vs 2.7%), hypoechogenicity (46.0% vs 6.8%), power Doppler positivity (43.0% vs 8.1%), and periostosis (43.0% vs 8.1%), being significantly more prevalent in patients with PsA vs RA (all P < .001).

Study details: Findings are from a cross-sectional observational study including patients with PsA (n = 23) and RA (n = 37) who reported painful ankles and control individuals (n = 20) without rheumatic disease or ankle pain.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Forien M et al. Ankle retinacula abnormalities as features of psoriatic arthritis: An ultrasound study. Joint Bone Spine. 2023 (Oct 4). doi: 10.1016/j.jbspin.2023.105649

Key clinical point: Ultrasound assessment of individuals with painful ankles revealed that abnormalities of the flexor retinacula (FR) were more common in patients with psoriatic arthritis (PsA) vs rheumatoid arthritis (RA).

Major finding: The FR were thicker in patients with PsA vs patients with RA and control individuals (0.96 vs 0.64 and 0.56, respectively; both P < .001), with abnormalities, such as retinaculitis (39.0% vs 2.7%), hypoechogenicity (46.0% vs 6.8%), power Doppler positivity (43.0% vs 8.1%), and periostosis (43.0% vs 8.1%), being significantly more prevalent in patients with PsA vs RA (all P < .001).

Study details: Findings are from a cross-sectional observational study including patients with PsA (n = 23) and RA (n = 37) who reported painful ankles and control individuals (n = 20) without rheumatic disease or ankle pain.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Forien M et al. Ankle retinacula abnormalities as features of psoriatic arthritis: An ultrasound study. Joint Bone Spine. 2023 (Oct 4). doi: 10.1016/j.jbspin.2023.105649

Key clinical point: This Mendelian randomization (MR) analysis established that there exists no causal association between psoriatic arthritis (PsA) and the genetic risk for skin cancer.

Major finding: PsA did not increase the genetic susceptibility to cutaneous squamous cell carcinoma (odds ratio [OR] 1.00; P = .214) and cutaneous melanoma (OR 1.00; P = .477). Although PsA decreased the genetic risk for basal cell carcinoma (OR 0.94; P = .016), the association disappeared when skin cancer risk factors like skin tanning, radiation-related disorders, and telomere length were considered.

Study details: Findings are from a multivariate MR analysis including 3186 patients with PsA and 240,862 control individuals without PsA.

Disclosures: This study was supported by the Natural Science Foundation of China and the Youth Science Foundation of Xiangya Hospital. The authors declared no conflicts of interest.

Source: Yu N et al. Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer. Front Immunol. 2023;14:1252720 (Sep 19). doi: 10.3389/fimmu.2023.1252720

Key clinical point: This Mendelian randomization (MR) analysis established that there exists no causal association between psoriatic arthritis (PsA) and the genetic risk for skin cancer.

Major finding: PsA did not increase the genetic susceptibility to cutaneous squamous cell carcinoma (odds ratio [OR] 1.00; P = .214) and cutaneous melanoma (OR 1.00; P = .477). Although PsA decreased the genetic risk for basal cell carcinoma (OR 0.94; P = .016), the association disappeared when skin cancer risk factors like skin tanning, radiation-related disorders, and telomere length were considered.

Study details: Findings are from a multivariate MR analysis including 3186 patients with PsA and 240,862 control individuals without PsA.

Disclosures: This study was supported by the Natural Science Foundation of China and the Youth Science Foundation of Xiangya Hospital. The authors declared no conflicts of interest.

Source: Yu N et al. Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer. Front Immunol. 2023;14:1252720 (Sep 19). doi: 10.3389/fimmu.2023.1252720

Key clinical point: This Mendelian randomization (MR) analysis established that there exists no causal association between psoriatic arthritis (PsA) and the genetic risk for skin cancer.

Major finding: PsA did not increase the genetic susceptibility to cutaneous squamous cell carcinoma (odds ratio [OR] 1.00; P = .214) and cutaneous melanoma (OR 1.00; P = .477). Although PsA decreased the genetic risk for basal cell carcinoma (OR 0.94; P = .016), the association disappeared when skin cancer risk factors like skin tanning, radiation-related disorders, and telomere length were considered.

Study details: Findings are from a multivariate MR analysis including 3186 patients with PsA and 240,862 control individuals without PsA.

Disclosures: This study was supported by the Natural Science Foundation of China and the Youth Science Foundation of Xiangya Hospital. The authors declared no conflicts of interest.

Source: Yu N et al. Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer. Front Immunol. 2023;14:1252720 (Sep 19). doi: 10.3389/fimmu.2023.1252720

Key clinical point: Difficult-to-treat (D2T) psoriatic arthritis (PsA), a condition characterized by the failure of ≥2 targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARD), is associated with a higher prevalence of axial involvement, structural damage, and treatment discontinuation.

Major finding: Peripheral structural damage (odds ratio [OR] 2.57; P = .020), axial involvement (OR 2.37; P = .035), and the discontinuation of bDMARD due to poor dermatological control (OR 2.99; P = .008) were more prevalent in patients with D2T PsA vs non-D2T PsA.

Study details: Findings are from a retrospective cohort study including 150 patients with PsA who initiated treatment with ts/bDMARD and were followed up for ≥2 years, of whom 49 patients had D2T PsA.

Disclosures: This study did not receive any funding. Three authors declared receiving honorary fees or research grants or serving as advisory board members for various sources.

Source: Philippoteaux C et al. Characteristics of difficult-to-treat psoriatic arthritis: A comparative analysis. Semin Arthritis Rheum. 2023;63:152275 (Oct 5). doi: 10.1016/j.semarthrit.2023.152275

Key clinical point: Difficult-to-treat (D2T) psoriatic arthritis (PsA), a condition characterized by the failure of ≥2 targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARD), is associated with a higher prevalence of axial involvement, structural damage, and treatment discontinuation.

Major finding: Peripheral structural damage (odds ratio [OR] 2.57; P = .020), axial involvement (OR 2.37; P = .035), and the discontinuation of bDMARD due to poor dermatological control (OR 2.99; P = .008) were more prevalent in patients with D2T PsA vs non-D2T PsA.

Study details: Findings are from a retrospective cohort study including 150 patients with PsA who initiated treatment with ts/bDMARD and were followed up for ≥2 years, of whom 49 patients had D2T PsA.

Disclosures: This study did not receive any funding. Three authors declared receiving honorary fees or research grants or serving as advisory board members for various sources.

Source: Philippoteaux C et al. Characteristics of difficult-to-treat psoriatic arthritis: A comparative analysis. Semin Arthritis Rheum. 2023;63:152275 (Oct 5). doi: 10.1016/j.semarthrit.2023.152275

Key clinical point: Difficult-to-treat (D2T) psoriatic arthritis (PsA), a condition characterized by the failure of ≥2 targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARD), is associated with a higher prevalence of axial involvement, structural damage, and treatment discontinuation.

Major finding: Peripheral structural damage (odds ratio [OR] 2.57; P = .020), axial involvement (OR 2.37; P = .035), and the discontinuation of bDMARD due to poor dermatological control (OR 2.99; P = .008) were more prevalent in patients with D2T PsA vs non-D2T PsA.

Study details: Findings are from a retrospective cohort study including 150 patients with PsA who initiated treatment with ts/bDMARD and were followed up for ≥2 years, of whom 49 patients had D2T PsA.

Disclosures: This study did not receive any funding. Three authors declared receiving honorary fees or research grants or serving as advisory board members for various sources.

Source: Philippoteaux C et al. Characteristics of difficult-to-treat psoriatic arthritis: A comparative analysis. Semin Arthritis Rheum. 2023;63:152275 (Oct 5). doi: 10.1016/j.semarthrit.2023.152275