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Does Acalabrutinib Fit Into Frontline MCL Therapy?
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
However, treating patients with bendamustine/rituximab plus acalabrutinib might be preferred to either option with cytarabine.
Although the results showed that the bendamustine/rituximab plus acalabrutinib regimen was not superior to standard induction therapy with or without acalabrutinib, it was the least toxic option.
Standard induction therapy can be still be considered the standard for this patient population, but eliminating cytarabine represents “an appealing option to avoid high-dose cytarabine,” said study investigator Nina Wagner-Johnston, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland, during a presentation of the findings at the American Society of Hematology 2024 annual meeting.
The bendamustine/rituximab plus acalabrutinib regimen, where acalabrutinib replaced high-dose cytarabine, is “the most intriguing arm of the study,” Marcus Messmer, MD, with the Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in an interview.
“The results suggest that bendamustine/rituximab plus acalabrutinib may be equivalent in efficacy to [standard induction] with less toxicity,” said Messmer, who was not involved in the study.
Unfortunately, the study was not designed to show noninferiority of bendamustine/rituximab plus acalabrutinib compared to standard induction therapy, and the bendamustine/rituximab plus acalabrutinib arm was stopped early because of a lack of a superiority signal, Messmer added.
Inside the Findings
MCL is a rare and aggressive B-cell lymphoma that poses unique treatment challenges, particularly in younger patients, for whom the treatment “landscape is shifting rapidly,” Wagner-Johnston explained.
Wagner-Johnston noted that the optimal induction regimen for fit, younger patients with MCL is unclear, although the mainstay of treatment is intensive chemoimmunotherapy with cytarabine.
The standard bendamustine/rituximab followed by cytarabine/rituximab induction regimen is associated with high complete remission and undetectable measurable residual disease, with evidence of improved progression-free survival, she noted.
“And we know that BTK inhibitors, in combination with chemoimmunotherapy, are highly effective in MCL and that achieving molecular remission or undetectable measurable residual disease is an independent predictor of long-term outcomes in patients. All of these features were key when designing ECOG-ACRIN EA 4181,” Wagner-Johnston told attendees.
The study enrolled 369 patients, 18-70 years old, with untreated MCL, ECOG performance score 0-2, and adequate organ and marrow function. Study participants were randomized 1:1:1 to the standard induction control arm or to one of two experimental arms. These included the control arm of induction therapy with three cycles of bendamustine/rituximab followed by three cycles of cytarabine/rituximab, the standard induction plus acalabrutinib across both cycles, or six cycles of bendamustine/rituximab with acalabrutinib.
In the standard induction plus acalabrutinib arm, acalabrutinib was dosed continuously at 100 mg twice daily during the initial cycles, and during weeks 1 and 3 of the latter cycles.
The primary analysis focused on 260 patients with an end-of-treatment sample sent for measurable residual disease testing. Roughly 90% of patients completed study treatment, with no differences between treatment arms.
The primary outcome was a composite of PET/CT complete molecular remission and peripheral blood undetectable measurable residual disease. In the control arm, 82% of patients achieved the primary outcome, as did 82% of patients in the standard induction plus acalabrutinib arm and 78% in the bendamustine/rituximab plus acalabrutinib arm.
“Notably, neither of the experimental arms were superior to the standard-of-care arm across the board,” Wagner-Johnston said. Overall response rates were “quite high,” with complete response rates of more than 90%, with no differences between the arms.
Similarly, no significant difference was seen in progression-free survival or overall survival between treatment arms. At a medium follow up of roughly 28 months, the 12-month progression-free survival rate was 90%-92% across the three groups.
The team also evaluated progression-free survival by measurable residual disease status, regardless of whether patients completed protocol therapy. “Not surprisingly,” said Wagner-Johnston, progression-free survival was superior for those with undetectable measurable residual disease, compared with those with detectable levels — but again there was no differences between treatment arms.
Grades 3-5 treatment-related adverse events occurred in at least 5% of patients and were mostly hematologic.
The bendamustine/rituximab plus acalabrutinib was associated with significantly less hematologic toxicity, with a febrile neutropenia rate of 4.0% vs 8.9% in the standard induction arm and 9.3% in the standard induction plus acalabrutinib arm.
Grades 3-5 treatment-related anemia rates were much lower in the bendamustine/rituximab plus acalabrutinib arm (3.0% vs 18.5% for standard induction and 24.8% for standard plus cytarabine). Similarly, the bendamustine/rituximab plus acalabrutinib arm had lower rates of treatment-related grade 3 or higher thrombocytopenia (6.0% vs 44.4% and 51.2%, respectively).
Across all three treatment groups, rates of neurotoxicity, renal toxicity, bleeding/hemorrhage, and cardiac toxicity were low.
Treatment discontinuations due to adverse events were also low (7%) across the arms, with five treatment-related deaths reported.
“Standard high-dose cytarabine requires inpatient administration and carries risk of neurologic and hematologic toxicity, making it particularly difficult to give in a community setting,” Marcus said in an interview. “This study, along with updated results from the TRIANGLE study, suggests that we are moving away from high-dose cytotoxic therapy and toward targeted therapy in frontline management of mantle cell lymphoma.”
The study was supported by the National Cancer Institute. Wagner-Johnston has received research founding from Genentech, Merck, and AstraZenecca and consults for Beigene. Marcus had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ASH 2024
Rilzabrutinib Shines in Phase 3 Trial of Tough-to-Treat Immune Thrombocytopenia
In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia.
Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.
Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”
The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”
Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue.
“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release.
Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025.
In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.
Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13.
The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy.
No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).
For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff.
Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).
Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.
Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).
Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).
“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing.
The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.
“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release.
The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia.
Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.
Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”
The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”
Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue.
“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release.
Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025.
In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.
Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13.
The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy.
No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).
For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff.
Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).
Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.
Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).
Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).
“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing.
The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.
“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release.
The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia.
Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.
Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”
The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”
Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue.
“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release.
Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025.
In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.
Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13.
The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy.
No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).
For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff.
Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).
Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.
Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).
Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).
“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing.
The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.
“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release.
The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.
A version of this article first appeared on Medscape.com.
FROM ASH 2024
Common Herbicide a Player in Neurodegeneration?
new research showed.
Researchers found that glyphosate exposure even at regulated levels was associated with increased neuroinflammation and accelerated Alzheimer’s disease–like pathology in mice — an effect that persisted 6 months after a recovery period when exposure was stopped.
“More research is needed to understand the consequences of glyphosate exposure to the brain in humans and to understand the appropriate dose of exposure to limit detrimental outcomes,” said co–senior author Ramon Velazquez, PhD, with Arizona State University, Tempe.
The study was published online in The Journal of Neuroinflammation.
Persistent Accumulation Within the Brain
Glyphosate is the most heavily applied herbicide in the United States, with roughly 300 million pounds used annually in agricultural communities throughout the United States. It is also used for weed control in parks, residential areas, and personal gardens.
The Environmental Protection Agency (EPA) has determined that glyphosate poses no risks to human health when used as directed. But the World Health Organization’s International Agency for Research on Cancer disagrees, classifying the herbicide as “possibly carcinogenic to humans.”
In addition to the possible cancer risk, multiple reports have also suggested potential harmful effects of glyphosate exposure on the brain.
In earlier work, Velazquez and colleagues showed that glyphosate crosses the blood-brain barrier and infiltrates the brains of mice, contributing to neuroinflammation and other detrimental effects on brain function.
In their latest study, they examined the long-term effects of glyphosate exposure on neuroinflammation and Alzheimer’s disease–like pathology using a mouse model.
They dosed 4.5-month-old mice genetically predisposed to Alzheimer’s disease and non-transgenic control mice with either 0, 50, or 500 mg/kg of glyphosate daily for 13 weeks followed by a 6-month recovery period.
The high dose is similar to levels used in earlier research, and the low dose is close to the limit used to establish the current EPA acceptable dose in humans.
Glyphosate’s metabolite, aminomethylphosphonic acid, was detectable and persisted in mouse brain tissue even 6 months after exposure ceased, the researchers reported.
Additionally, there was a significant increase in soluble and insoluble fractions of amyloid-beta (Abeta), Abeta42 plaque load and plaque size, and phosphorylated tau at Threonine 181 and Serine 396 in hippocampus and cortex brain tissue from glyphosate-exposed mice, “highlighting an exacerbation of hallmark Alzheimer’s disease–like proteinopathies,” they noted.
Glyphosate exposure was also associated with significant elevations in both pro- and anti-inflammatory cytokines and chemokines in brain tissue of transgenic and normal mice and in peripheral blood plasma of transgenic mice.
Glyphosate-exposed transgenic mice also showed heightened anxiety-like behaviors and reduced survival.
“These findings highlight that many chemicals we regularly encounter, previously considered safe, may pose potential health risks,” co–senior author Patrick Pirrotte, PhD, with the Translational Genomics Research Institute, Phoenix, Arizona, said in a statement.
“However, further research is needed to fully assess the public health impact and identify safer alternatives,” Pirrotte added.
Funding for the study was provided by the National Institutes on Aging, National Cancer Institute and the Arizona State University (ASU) Biodesign Institute. The authors have declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
new research showed.
Researchers found that glyphosate exposure even at regulated levels was associated with increased neuroinflammation and accelerated Alzheimer’s disease–like pathology in mice — an effect that persisted 6 months after a recovery period when exposure was stopped.
“More research is needed to understand the consequences of glyphosate exposure to the brain in humans and to understand the appropriate dose of exposure to limit detrimental outcomes,” said co–senior author Ramon Velazquez, PhD, with Arizona State University, Tempe.
The study was published online in The Journal of Neuroinflammation.
Persistent Accumulation Within the Brain
Glyphosate is the most heavily applied herbicide in the United States, with roughly 300 million pounds used annually in agricultural communities throughout the United States. It is also used for weed control in parks, residential areas, and personal gardens.
The Environmental Protection Agency (EPA) has determined that glyphosate poses no risks to human health when used as directed. But the World Health Organization’s International Agency for Research on Cancer disagrees, classifying the herbicide as “possibly carcinogenic to humans.”
In addition to the possible cancer risk, multiple reports have also suggested potential harmful effects of glyphosate exposure on the brain.
In earlier work, Velazquez and colleagues showed that glyphosate crosses the blood-brain barrier and infiltrates the brains of mice, contributing to neuroinflammation and other detrimental effects on brain function.
In their latest study, they examined the long-term effects of glyphosate exposure on neuroinflammation and Alzheimer’s disease–like pathology using a mouse model.
They dosed 4.5-month-old mice genetically predisposed to Alzheimer’s disease and non-transgenic control mice with either 0, 50, or 500 mg/kg of glyphosate daily for 13 weeks followed by a 6-month recovery period.
The high dose is similar to levels used in earlier research, and the low dose is close to the limit used to establish the current EPA acceptable dose in humans.
Glyphosate’s metabolite, aminomethylphosphonic acid, was detectable and persisted in mouse brain tissue even 6 months after exposure ceased, the researchers reported.
Additionally, there was a significant increase in soluble and insoluble fractions of amyloid-beta (Abeta), Abeta42 plaque load and plaque size, and phosphorylated tau at Threonine 181 and Serine 396 in hippocampus and cortex brain tissue from glyphosate-exposed mice, “highlighting an exacerbation of hallmark Alzheimer’s disease–like proteinopathies,” they noted.
Glyphosate exposure was also associated with significant elevations in both pro- and anti-inflammatory cytokines and chemokines in brain tissue of transgenic and normal mice and in peripheral blood plasma of transgenic mice.
Glyphosate-exposed transgenic mice also showed heightened anxiety-like behaviors and reduced survival.
“These findings highlight that many chemicals we regularly encounter, previously considered safe, may pose potential health risks,” co–senior author Patrick Pirrotte, PhD, with the Translational Genomics Research Institute, Phoenix, Arizona, said in a statement.
“However, further research is needed to fully assess the public health impact and identify safer alternatives,” Pirrotte added.
Funding for the study was provided by the National Institutes on Aging, National Cancer Institute and the Arizona State University (ASU) Biodesign Institute. The authors have declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
new research showed.
Researchers found that glyphosate exposure even at regulated levels was associated with increased neuroinflammation and accelerated Alzheimer’s disease–like pathology in mice — an effect that persisted 6 months after a recovery period when exposure was stopped.
“More research is needed to understand the consequences of glyphosate exposure to the brain in humans and to understand the appropriate dose of exposure to limit detrimental outcomes,” said co–senior author Ramon Velazquez, PhD, with Arizona State University, Tempe.
The study was published online in The Journal of Neuroinflammation.
Persistent Accumulation Within the Brain
Glyphosate is the most heavily applied herbicide in the United States, with roughly 300 million pounds used annually in agricultural communities throughout the United States. It is also used for weed control in parks, residential areas, and personal gardens.
The Environmental Protection Agency (EPA) has determined that glyphosate poses no risks to human health when used as directed. But the World Health Organization’s International Agency for Research on Cancer disagrees, classifying the herbicide as “possibly carcinogenic to humans.”
In addition to the possible cancer risk, multiple reports have also suggested potential harmful effects of glyphosate exposure on the brain.
In earlier work, Velazquez and colleagues showed that glyphosate crosses the blood-brain barrier and infiltrates the brains of mice, contributing to neuroinflammation and other detrimental effects on brain function.
In their latest study, they examined the long-term effects of glyphosate exposure on neuroinflammation and Alzheimer’s disease–like pathology using a mouse model.
They dosed 4.5-month-old mice genetically predisposed to Alzheimer’s disease and non-transgenic control mice with either 0, 50, or 500 mg/kg of glyphosate daily for 13 weeks followed by a 6-month recovery period.
The high dose is similar to levels used in earlier research, and the low dose is close to the limit used to establish the current EPA acceptable dose in humans.
Glyphosate’s metabolite, aminomethylphosphonic acid, was detectable and persisted in mouse brain tissue even 6 months after exposure ceased, the researchers reported.
Additionally, there was a significant increase in soluble and insoluble fractions of amyloid-beta (Abeta), Abeta42 plaque load and plaque size, and phosphorylated tau at Threonine 181 and Serine 396 in hippocampus and cortex brain tissue from glyphosate-exposed mice, “highlighting an exacerbation of hallmark Alzheimer’s disease–like proteinopathies,” they noted.
Glyphosate exposure was also associated with significant elevations in both pro- and anti-inflammatory cytokines and chemokines in brain tissue of transgenic and normal mice and in peripheral blood plasma of transgenic mice.
Glyphosate-exposed transgenic mice also showed heightened anxiety-like behaviors and reduced survival.
“These findings highlight that many chemicals we regularly encounter, previously considered safe, may pose potential health risks,” co–senior author Patrick Pirrotte, PhD, with the Translational Genomics Research Institute, Phoenix, Arizona, said in a statement.
“However, further research is needed to fully assess the public health impact and identify safer alternatives,” Pirrotte added.
Funding for the study was provided by the National Institutes on Aging, National Cancer Institute and the Arizona State University (ASU) Biodesign Institute. The authors have declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF NEUROINFLAMMATION
CRC Screening Uptake Rises in Adults Aged 45-49 Years
TOPLINE:
but disparities by socioeconomic status and locality occurred.
METHODOLOGY:
- Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
- They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
- They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.
TAKEAWAY:
- Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
- Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
- The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
- The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
- By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.
IN PRACTICE:
“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.
SOURCE:
The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open.
LIMITATIONS:
Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.
DISCLOSURES:
The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
but disparities by socioeconomic status and locality occurred.
METHODOLOGY:
- Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
- They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
- They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.
TAKEAWAY:
- Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
- Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
- The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
- The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
- By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.
IN PRACTICE:
“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.
SOURCE:
The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open.
LIMITATIONS:
Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.
DISCLOSURES:
The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
but disparities by socioeconomic status and locality occurred.
METHODOLOGY:
- Researchers compared absolute and relative changes in screening uptake among average-risk adults 45-49 years between a 20-month period before and a 20-month period after the USPSTF recommendation was issued (May 1, 2018, to December 31, 2019, and May 1, 2021, to December 31, 2022). Data was evaluated bimonthly.
- They analyzed claims data from more than 10.2 million people with private Blue Cross Blue Shield (BCBS) coverage, with about three million eligible for screening during each bimonthly period, both pre- and post-recommendation.
- They used interrupted time-series analysis and autoregressive integrated moving average models to gauge changes in screening rates.
TAKEAWAY:
- Mean CRC screening uptake in average-risk adults 45-49 years increased from 0.50% in the pre-recommendation period to 1.51% post-recommendation, reflecting a significant absolute change of 1.01 percentage points but no significant relative change.
- Adults 45-49 years living in areas with the highest socioeconomic status (SES) had the largest absolute change in screening uptake compared with peers in the lowest SES areas (1.25 vs 0.75 percentage points). Relative changes were not significant.
- The absolute change in screening uptake was higher among individuals in metropolitan areas than individuals in nonmetropolitan areas (1.06 vs 0.73 percentage points). Again, relative changes were not significant.
- The screening uptake rate increased the fastest among those living in the highest SES and metropolitan areas (0.24 and 0.20 percentage points every 2 months, respectively).
- By December 2022 (the end of the post-recommendation period), CRC screening uptake among adults 45-49 years were on par with those seen in adults 50-75 years (2.37% vs 2.4%). Nonetheless, only 11.5% of average-risk adults aged 45-49 years received CRC screening during the post-recommendation period.
IN PRACTICE:
“The threefold increase in screening uptake among average-risk individuals aged 45-49 years reflects an accomplishment, yet evidence of widening disparities based on SDI [Social Deprivation Index] and locality indicate that population subgroups may not be benefiting equally from this change in CRC screening recommendation. Furthermore, given that only 11.5% of average-risk individuals aged 45-49 years during the post-recommendation period received CRC screening before the age of 50 years, targeted initiatives to improve screening in this age group are warranted to reach the national goal of screening 80% of the population in every community,” the researchers wrote.
SOURCE:
The study, with first author Sunny Siddique, MPH, with Yale School of Public Health, New Haven, Connecticut, was published online in JAMA Network Open.
LIMITATIONS:
Data on race and ethnicity were incomplete, which may have impacted the analysis of disparities. The study cohort may not be fully representative of the general US population because BCBS beneficiaries tend to be younger and more socioeconomically advantaged with employer-based insurance. Specific information on the type of coverage provided by each beneficiary’s insurance plan was not available.
DISCLOSURES:
The study was funded by the National Cancer Institute. The authors declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
NCCN Expands Cancer Genetic Risk Assessment Guidelines
Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.
For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.
“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.
Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.
The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants.
For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.”
“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release.
“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.
A version of this article first appeared on Medscape.com.
Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.
For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.
“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.
Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.
The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants.
For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.”
“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release.
“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.
A version of this article first appeared on Medscape.com.
Additional cancer types were included in the title and content for both guidelines. Prostate cancer was added to Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate, and endometrial and gastric cancer were added to Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric.
For these cancers, the expanded guidelines include information on when genetic testing is recommended and what type of testing may be best. These guidelines also detail the hereditary conditions and genetic mutations associated with elevated cancer risk and include appropriate “next steps” for individuals who have them, which may involve increased screening or prevention surgeries.
“These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward,” Mary B. Daly, MD, PhD, with Fox Chase Cancer Center, Philadelphia, Pennsylvania, said in a news release. Daly chaired the panel that updated the breast, ovarian, pancreatic, and prostate cancer guidelines.
Oncologists should, for instance, ask patients about their family and personal history of cancer and known germline variants at time of initial diagnosis. With prostate cancer, if patients meet criteria for germline testing, multigene testing should include a host of variants, including BRCA1, BRCA2, ATM, PALB2, CHEK2, HOXB13, MLH1, MSH2, MSH6, and PMS2.
The updated guidelines on genetic risk assessment of colorectal, endometrial, and gastric cancer include new recommendations to consider for hereditary cancer screening in patients with newly diagnosed endometrial cancer, for evaluating and managing CDH1-associated gastric cancer risk, and for managing gastric cancer risk in patients with APC pathogenic variants.
For CDH1-associated gastric cancer, for instance, the guidelines recommend carriers be referred to institutions with expertise in managing risks for cancer associated with CDH1, “given the still limited understanding and rarity of this syndrome.”
“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” said NCCN CEO Crystal S. Denlinger, MD, with Fox Chase Cancer Center, in a news release.
“This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members,” Denlinger added.
A version of this article first appeared on Medscape.com.
Prostate Cancer: Has Active Surveillance Solved the Problem of Overtreatment?
“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.
The study was published online on November 11 in JAMA Internal Medicine.
‘Concerning’ Real-World Data
For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.
Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.
About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.
Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.
Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.
Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.
“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said in an interview.
Is This Happening in the General US Population?
Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.
“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.
“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.
Is Overtreatment All Bad?
Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.
In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.
“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he said.
Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.
Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.
The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.
Tough to Talk About?
Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.
Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.
Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.
He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.
“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.
This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.
A version of this article appeared on Medscape.com.
“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.
The study was published online on November 11 in JAMA Internal Medicine.
‘Concerning’ Real-World Data
For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.
Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.
About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.
Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.
Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.
Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.
“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said in an interview.
Is This Happening in the General US Population?
Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.
“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.
“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.
Is Overtreatment All Bad?
Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.
In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.
“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he said.
Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.
Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.
The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.
Tough to Talk About?
Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.
Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.
Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.
He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.
“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.
This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.
A version of this article appeared on Medscape.com.
“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.
The study was published online on November 11 in JAMA Internal Medicine.
‘Concerning’ Real-World Data
For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.
Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.
About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.
Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.
Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.
Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.
“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said in an interview.
Is This Happening in the General US Population?
Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.
“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.
“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.
Is Overtreatment All Bad?
Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.
In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.
“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he said.
Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.
Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.
The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.
Tough to Talk About?
Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.
Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.
Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.
He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.
“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.
This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.
A version of this article appeared on Medscape.com.
How Do Novel CRC Blood Tests Fare Against Established Tests?
TOPLINE:
METHODOLOGY:
- Researchers estimated the clinical and economic impacts of emerging blood- and stool-based CRC screening tests with established alternatives in average-risk adults aged 45 years and older.
- The established screening tools were colonoscopy, a fecal immunochemical test (FIT), and a multitarget stool DNA test (MT-sDNA, Exact Sciences Cologuard).
- The four emerging screening methods were two cf-bDNA tests (Guardant Shield and Freenome); an enhanced, a next-generation multitarget stool test (ngMT-sDNA), and a novel FIT-RNA test (Geneoscopy ColoSense).
TAKEAWAY:
- Assuming 100% participation in all screening steps, colonoscopy and FIT yielded reductions of more than 70% in CRC incidence and 75% in mortality vs no screening.
- The MT-sDNA test reduced CRC incidence by 68% and mortality by 73%, with similar rates for the ngMT-sDNA and FIT-RNA tests vs no screening. The cf-bDNA tests yielded CRC incidence and mortality reductions of only 42% and 56%.
- Colonoscopy and FIT were more effective and less costly than the cf-bDNA and MT-sDNA tests, and the MT-sDNA test was more effective and less costly than the cf-bDNA test.
- Population benefits from blood tests were seen only in those who declined colonoscopy and stool tests. Substituting a blood test for those already using colonoscopy or stool tests led to worse population-level outcomes.
IN PRACTICE:
“First-generation novel cf-bDNA tests have the potential to decrease meaningfully the incidence and mortality of CRC compared with no screening but substantially less profoundly than screening colonoscopy or stool tests. Net population benefit or harm can follow incorporation of first-generation cf-bDNA CRC screening tests into practice, depending on the balance between bringing unscreened persons into screening (addition) vs shifting persons away from the more effective strategies of colonoscopy or stool testing (substitution),” the authors concluded.
SOURCE:
The study, with first author Uri Ladabaum, MD, MS, Stanford University School of Medicine, California, was published online in Annals of Internal Medicine.
LIMITATIONS:
Limitations included test-specific participation patterns being unknown over time.
DISCLOSURES:
Disclosure forms for the authors are available with the article online. Funding was provided by the Gorrindo Family Fund.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers estimated the clinical and economic impacts of emerging blood- and stool-based CRC screening tests with established alternatives in average-risk adults aged 45 years and older.
- The established screening tools were colonoscopy, a fecal immunochemical test (FIT), and a multitarget stool DNA test (MT-sDNA, Exact Sciences Cologuard).
- The four emerging screening methods were two cf-bDNA tests (Guardant Shield and Freenome); an enhanced, a next-generation multitarget stool test (ngMT-sDNA), and a novel FIT-RNA test (Geneoscopy ColoSense).
TAKEAWAY:
- Assuming 100% participation in all screening steps, colonoscopy and FIT yielded reductions of more than 70% in CRC incidence and 75% in mortality vs no screening.
- The MT-sDNA test reduced CRC incidence by 68% and mortality by 73%, with similar rates for the ngMT-sDNA and FIT-RNA tests vs no screening. The cf-bDNA tests yielded CRC incidence and mortality reductions of only 42% and 56%.
- Colonoscopy and FIT were more effective and less costly than the cf-bDNA and MT-sDNA tests, and the MT-sDNA test was more effective and less costly than the cf-bDNA test.
- Population benefits from blood tests were seen only in those who declined colonoscopy and stool tests. Substituting a blood test for those already using colonoscopy or stool tests led to worse population-level outcomes.
IN PRACTICE:
“First-generation novel cf-bDNA tests have the potential to decrease meaningfully the incidence and mortality of CRC compared with no screening but substantially less profoundly than screening colonoscopy or stool tests. Net population benefit or harm can follow incorporation of first-generation cf-bDNA CRC screening tests into practice, depending on the balance between bringing unscreened persons into screening (addition) vs shifting persons away from the more effective strategies of colonoscopy or stool testing (substitution),” the authors concluded.
SOURCE:
The study, with first author Uri Ladabaum, MD, MS, Stanford University School of Medicine, California, was published online in Annals of Internal Medicine.
LIMITATIONS:
Limitations included test-specific participation patterns being unknown over time.
DISCLOSURES:
Disclosure forms for the authors are available with the article online. Funding was provided by the Gorrindo Family Fund.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Researchers estimated the clinical and economic impacts of emerging blood- and stool-based CRC screening tests with established alternatives in average-risk adults aged 45 years and older.
- The established screening tools were colonoscopy, a fecal immunochemical test (FIT), and a multitarget stool DNA test (MT-sDNA, Exact Sciences Cologuard).
- The four emerging screening methods were two cf-bDNA tests (Guardant Shield and Freenome); an enhanced, a next-generation multitarget stool test (ngMT-sDNA), and a novel FIT-RNA test (Geneoscopy ColoSense).
TAKEAWAY:
- Assuming 100% participation in all screening steps, colonoscopy and FIT yielded reductions of more than 70% in CRC incidence and 75% in mortality vs no screening.
- The MT-sDNA test reduced CRC incidence by 68% and mortality by 73%, with similar rates for the ngMT-sDNA and FIT-RNA tests vs no screening. The cf-bDNA tests yielded CRC incidence and mortality reductions of only 42% and 56%.
- Colonoscopy and FIT were more effective and less costly than the cf-bDNA and MT-sDNA tests, and the MT-sDNA test was more effective and less costly than the cf-bDNA test.
- Population benefits from blood tests were seen only in those who declined colonoscopy and stool tests. Substituting a blood test for those already using colonoscopy or stool tests led to worse population-level outcomes.
IN PRACTICE:
“First-generation novel cf-bDNA tests have the potential to decrease meaningfully the incidence and mortality of CRC compared with no screening but substantially less profoundly than screening colonoscopy or stool tests. Net population benefit or harm can follow incorporation of first-generation cf-bDNA CRC screening tests into practice, depending on the balance between bringing unscreened persons into screening (addition) vs shifting persons away from the more effective strategies of colonoscopy or stool testing (substitution),” the authors concluded.
SOURCE:
The study, with first author Uri Ladabaum, MD, MS, Stanford University School of Medicine, California, was published online in Annals of Internal Medicine.
LIMITATIONS:
Limitations included test-specific participation patterns being unknown over time.
DISCLOSURES:
Disclosure forms for the authors are available with the article online. Funding was provided by the Gorrindo Family Fund.
A version of this article appeared on Medscape.com.
Endoscopic Sleeve Gastroplasty Yields Durable Weight Loss at 10 Years
PHILADELPHIA —
“The procedure is dependable and safe and should be considered among individuals who have not attained their desired results through lifestyle medications and those who are not eligible for or choose not to undergo bariatric procedures,” said Ali Lahooti, with the Department of Gastroenterology and Hepatology, Weill Cornell Medical College, New York City. He presented his research at the annual meeting of the American College of Gastroenterology (ACG).
Obesity is a growing global health challenge. Lifestyle modification as a standalone therapy has limited effectiveness achieving weight loss. Pharmacotherapies are more efficacious, but they’re also associated with higher costs of and risk for side effects, leading to lower rates of compliance, Lahooti explained.
Bariatric surgery remains the most effective therapy for management of obesity and improvement of comorbid conditions, yet < 1% of candidates undergo a surgical intervention either because of access, cost, or fear of the procedure.
“Endoscopic treatments for obesity, such as ESG, can potentially fill this gap by combining durable weight loss with lower risk and costs,” Lahooti said.
He and his colleagues assessed outcomes out to 10 years in 404 patients (mean age, 45 years; 76% women; mean body mass index, 37.3) who underwent ESG between 2013 and 2024 at a single large tertiary hospital.
Out of the 404 patients, 397, 335, 249, and 110 patients were eligible for 1-, 3-, 5-, and 10-year follow-up, with complete follow-up rates of 85%, 66%, 79%, and 62%, respectively.
The primary outcome was weight loss at 10 years after ESG reported at percent total body weight loss (%TBWL).
At 10 years, mean %TBWL (the primary outcome) was 10.5% — with 53% of patients maintaining at least 5% TBWL and 42% maintaining at least 10% weight loss, Lahooti reported.
ESG had a favorable safety profile; 20% of patients experienced mild abdominal pain, constipation, heartburn, and nausea after the procedure that typically resolved within 2 weeks of the procedure.
“There were a total of three moderate adverse events — two perigastric leaks, one repaired endoscopically, and another that only required antibiotics,” Lahooti reported. There were no severe or fatal adverse events.
About 11% of patients had endoscopic revision via retightening or resuturing at 10 years, the study team noted in their conference abstract.
Bariatric Surgery Remains Gold Standard
Lahooti shared that in his experience, some patients will need a revision at “about 40 months,” but at the same time, he’s seen some patients at 10 years “and their sutures are still in place.”
Session comoderator Shivangi Kothari, MD, with the Center for Advanced Therapeutic Endoscopy, University of Rochester Medical Center in New York, congratulated Lahooti for providing “robust” long-term data on ESG and said, “there is a need for more studies like this.”
In an interview, Ann M. Rogers, MD, president of the American Society for Metabolic and Bariatric Surgery, noted that bariatric surgery remains the “gold standard for weight loss and metabolic improvements,” with studies showing “around 30%” TWBL at 10 years, compared with about 10% at 10 years in this study.
Another key caveat, said Rogers, is that there are practical barriers to ESG; insurance typically does not cover the procedure because they view it as “cosmetic.”
The study had no commercial funding. Lahooti and Rogers had no relevant disclosures.
A version of this article first appeared on Medscape.com.
PHILADELPHIA —
“The procedure is dependable and safe and should be considered among individuals who have not attained their desired results through lifestyle medications and those who are not eligible for or choose not to undergo bariatric procedures,” said Ali Lahooti, with the Department of Gastroenterology and Hepatology, Weill Cornell Medical College, New York City. He presented his research at the annual meeting of the American College of Gastroenterology (ACG).
Obesity is a growing global health challenge. Lifestyle modification as a standalone therapy has limited effectiveness achieving weight loss. Pharmacotherapies are more efficacious, but they’re also associated with higher costs of and risk for side effects, leading to lower rates of compliance, Lahooti explained.
Bariatric surgery remains the most effective therapy for management of obesity and improvement of comorbid conditions, yet < 1% of candidates undergo a surgical intervention either because of access, cost, or fear of the procedure.
“Endoscopic treatments for obesity, such as ESG, can potentially fill this gap by combining durable weight loss with lower risk and costs,” Lahooti said.
He and his colleagues assessed outcomes out to 10 years in 404 patients (mean age, 45 years; 76% women; mean body mass index, 37.3) who underwent ESG between 2013 and 2024 at a single large tertiary hospital.
Out of the 404 patients, 397, 335, 249, and 110 patients were eligible for 1-, 3-, 5-, and 10-year follow-up, with complete follow-up rates of 85%, 66%, 79%, and 62%, respectively.
The primary outcome was weight loss at 10 years after ESG reported at percent total body weight loss (%TBWL).
At 10 years, mean %TBWL (the primary outcome) was 10.5% — with 53% of patients maintaining at least 5% TBWL and 42% maintaining at least 10% weight loss, Lahooti reported.
ESG had a favorable safety profile; 20% of patients experienced mild abdominal pain, constipation, heartburn, and nausea after the procedure that typically resolved within 2 weeks of the procedure.
“There were a total of three moderate adverse events — two perigastric leaks, one repaired endoscopically, and another that only required antibiotics,” Lahooti reported. There were no severe or fatal adverse events.
About 11% of patients had endoscopic revision via retightening or resuturing at 10 years, the study team noted in their conference abstract.
Bariatric Surgery Remains Gold Standard
Lahooti shared that in his experience, some patients will need a revision at “about 40 months,” but at the same time, he’s seen some patients at 10 years “and their sutures are still in place.”
Session comoderator Shivangi Kothari, MD, with the Center for Advanced Therapeutic Endoscopy, University of Rochester Medical Center in New York, congratulated Lahooti for providing “robust” long-term data on ESG and said, “there is a need for more studies like this.”
In an interview, Ann M. Rogers, MD, president of the American Society for Metabolic and Bariatric Surgery, noted that bariatric surgery remains the “gold standard for weight loss and metabolic improvements,” with studies showing “around 30%” TWBL at 10 years, compared with about 10% at 10 years in this study.
Another key caveat, said Rogers, is that there are practical barriers to ESG; insurance typically does not cover the procedure because they view it as “cosmetic.”
The study had no commercial funding. Lahooti and Rogers had no relevant disclosures.
A version of this article first appeared on Medscape.com.
PHILADELPHIA —
“The procedure is dependable and safe and should be considered among individuals who have not attained their desired results through lifestyle medications and those who are not eligible for or choose not to undergo bariatric procedures,” said Ali Lahooti, with the Department of Gastroenterology and Hepatology, Weill Cornell Medical College, New York City. He presented his research at the annual meeting of the American College of Gastroenterology (ACG).
Obesity is a growing global health challenge. Lifestyle modification as a standalone therapy has limited effectiveness achieving weight loss. Pharmacotherapies are more efficacious, but they’re also associated with higher costs of and risk for side effects, leading to lower rates of compliance, Lahooti explained.
Bariatric surgery remains the most effective therapy for management of obesity and improvement of comorbid conditions, yet < 1% of candidates undergo a surgical intervention either because of access, cost, or fear of the procedure.
“Endoscopic treatments for obesity, such as ESG, can potentially fill this gap by combining durable weight loss with lower risk and costs,” Lahooti said.
He and his colleagues assessed outcomes out to 10 years in 404 patients (mean age, 45 years; 76% women; mean body mass index, 37.3) who underwent ESG between 2013 and 2024 at a single large tertiary hospital.
Out of the 404 patients, 397, 335, 249, and 110 patients were eligible for 1-, 3-, 5-, and 10-year follow-up, with complete follow-up rates of 85%, 66%, 79%, and 62%, respectively.
The primary outcome was weight loss at 10 years after ESG reported at percent total body weight loss (%TBWL).
At 10 years, mean %TBWL (the primary outcome) was 10.5% — with 53% of patients maintaining at least 5% TBWL and 42% maintaining at least 10% weight loss, Lahooti reported.
ESG had a favorable safety profile; 20% of patients experienced mild abdominal pain, constipation, heartburn, and nausea after the procedure that typically resolved within 2 weeks of the procedure.
“There were a total of three moderate adverse events — two perigastric leaks, one repaired endoscopically, and another that only required antibiotics,” Lahooti reported. There were no severe or fatal adverse events.
About 11% of patients had endoscopic revision via retightening or resuturing at 10 years, the study team noted in their conference abstract.
Bariatric Surgery Remains Gold Standard
Lahooti shared that in his experience, some patients will need a revision at “about 40 months,” but at the same time, he’s seen some patients at 10 years “and their sutures are still in place.”
Session comoderator Shivangi Kothari, MD, with the Center for Advanced Therapeutic Endoscopy, University of Rochester Medical Center in New York, congratulated Lahooti for providing “robust” long-term data on ESG and said, “there is a need for more studies like this.”
In an interview, Ann M. Rogers, MD, president of the American Society for Metabolic and Bariatric Surgery, noted that bariatric surgery remains the “gold standard for weight loss and metabolic improvements,” with studies showing “around 30%” TWBL at 10 years, compared with about 10% at 10 years in this study.
Another key caveat, said Rogers, is that there are practical barriers to ESG; insurance typically does not cover the procedure because they view it as “cosmetic.”
The study had no commercial funding. Lahooti and Rogers had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ACG 2024
Reassuring Data on GLP-1 RAs and Pancreatic Cancer Risk
PHILADELPHIA —
Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications.
“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin.
He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Important Topic
Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.
Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer.
A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones.
Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis.
The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.
The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).
Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.
The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.
Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.
The study had no specific funding. Alchirazi had no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA —
Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications.
“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin.
He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Important Topic
Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.
Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer.
A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones.
Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis.
The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.
The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).
Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.
The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.
Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.
The study had no specific funding. Alchirazi had no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA —
Instead, the large electronic health record (EHR) analysis of patients with type 2 diabetes (T2D) found those taking GLP-1 RAs had a significantly lower risk for pancreatic cancer than peers on other antidiabetic medications.
“Although there were previous reports suggesting possible association between pancreatic cancer and GLP-1 receptor agonist medications, this study provides reassurance that there is no observed increased incidence of pancreatic cancer in patients prescribed these medications,” said Khaled Alsabbagh Alchirazi, MD, a gastroenterology fellow with Aurora Healthcare in Brookfield, Wisconsin.
He presented the study findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Important Topic
Patients with T2D are at increased risk for several malignancies, including pancreatic cancer. Given the unique mechanism of action of GLP-1 RAs in the pancreas, it was important to investigate the relationship between use of these drugs and incidence of pancreatic cancer, he explained.
Using the TriNetX database, the study team identified 4.95 million antidiabetic drug naive T2D patients who were prescribed antidiabetic medications for the first time between 2005 and 2020. None had a history of pancreatic cancer.
A total of 245,532 were prescribed a GLP-1 RA. The researchers compared GLP-1 RAs users to users of other antidiabetic medications — namely, insulin, metformin, alpha-glucosidase inhibitors, dipeptidyl-peptidase 4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), sulfonylureas, and thiazolidinediones.
Patients were propensity score-matched based on demographics, health determinants, lifestyle factors, medical history, family history of cancers, and acute/chronic pancreatitis.
The risk for pancreatic cancer was significantly lower among patients on GLP-1 RAs vs insulin (hazard ratio [HR], 0.47; 95% CI, 0.40-0.55), DPP-4i (HR, 0.80; 95% CI, 0.73-0.89), SGLT2i (HR, 0.78; 95% CI, 0.69-0.89), and sulfonylureas (HR, 0.84; 95% CI, 0.74-0.95), Alchirazi reported.
The results were consistent across different groups, including patients with obesity/ overweight on GLP-1 RAs vs insulin (HR, 0.53; 95% CI, 0.43-0.65) and SGLT2i (HR, 0.81; 95% CI, 0.69-0.96).
Strengths of the analysis included the large and diverse cohort of propensity score-matched patients. Limitations included the retrospective design and use of claims data that did not provide granular data on pathology reports.
The study by Alchirazi and colleagues aligns with a large population-based cohort study from Israel that found no evidence that GLP-1 RAs increase risk for pancreatic cancer over 7 years following initiation.
Separately, a study of more than 1.6 million patients with T2D found that treatment with a GLP-1 RA (vs insulin or metformin) was associated with lower risks for specific types of obesity-related cancers, including pancreatic cancer.
The study had no specific funding. Alchirazi had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ACG 2024
Smokeless Tobacco, Areca Nut Chewing Behind 1 in 3 Oral Cancers: IARC Report
“Smokeless tobacco and areca nut products are available to consumers in many different forms across the world, but consuming smokeless tobacco and areca nut is linked to multiple diseases, including oral cancer,” Harriet Rumgay, PhD, a scientist in the Cancer Surveillance Branch at IARC and first author of the study in Lancet Oncology, said in a news release.
Worldwide, about 300 million people use smokeless tobacco and 600 million people use areca (also called betel) nut, one of the most popular psychoactive substances in the world after nicotine, alcohol, and caffeine. Smokeless tobacco products are consumed without burning and can be chewed, sucked, inhaled, applied locally, or ingested. Areca nut is the seed of the areca palm and can be consumed in various forms.
“Our estimates highlight the burden these products pose on health care and the importance of prevention strategies to reduce consumption of smokeless tobacco and areca nut,” Rumgay said.
According to the new report, in 2022, an estimated 120,200 of the 389,800 (30.8%) global cases of oral cancer were attributable to these products.
More than three quarters (77%) of attributable cases were among men and about one quarter (23%) among women.
The vast majority (96%) of all oral cancer cases caused by smokeless tobacco and areca nut use occurred in low- and middle-income countries.
Regions with the highest burden of oral cancers from these products were Southcentral Asia — with 105,500 of 120,200 cases (nearly 88%), including 83,400 in India, 9700 in Bangladesh, 8900 in Pakistan, and 1300 in Sri Lanka — followed by Southeastern Asia with a total of 3900 cases (1600 in Myanmar, 990 in Indonesia, and 785 in Thailand) and East Asia with 3300 cases (3200 in China).
Limitations and Action Points
The authors noted a limitation of the analysis is not accounting for the potential synergistic effects of combined use of smokeless tobacco or areca nut products with other risk factors for oral cancer, such as smoking tobacco or drinking alcohol.
The researchers explained that combined consumption of smokeless tobacco or areca nut, smoked tobacco, and alcohol has a “multiplicative effect” on oral cancer risk, with reported odds ratios increasing from 2.7 for smokeless tobacco only, 7.0 for smoked tobacco only, and 1.6 for alcohol only to 16.2 for all three exposures (vs no use).
However, the proportion of people who chewed tobacco and also smoked in countries with high smokeless tobacco or areca nut use was small. In India, for example, 6% of men and 0.5% of women in 2016-2017 were dual users of both smoked and smokeless tobacco, compared with 23% of men and 12% of women who only used smokeless tobacco.
Overall, curbing or preventing smokeless tobacco and areca nut use could help avoid many instances of oral cancer.
Despite “encouraging trends” in control of tobacco smoking in many regions of the world over the past two decades, progress in reducing the prevalence of smokeless tobacco consumption has stalled in many countries that are major consumers, the authors said.
Compounding the problem, areca nut does not fall within the WHO framework of tobacco control and there are very few areca nut control policies worldwide.
Smokeless tobacco control must be “prioritized” and a framework on areca nut control should be developed with guidelines to incorporate areca nut prevention into cancer control programs, the authors concluded.
Funding for the study was provided by the French National Cancer Institute. The authors had no relevant disclosures.
A version of this article first appeared on Medscape.com.
“Smokeless tobacco and areca nut products are available to consumers in many different forms across the world, but consuming smokeless tobacco and areca nut is linked to multiple diseases, including oral cancer,” Harriet Rumgay, PhD, a scientist in the Cancer Surveillance Branch at IARC and first author of the study in Lancet Oncology, said in a news release.
Worldwide, about 300 million people use smokeless tobacco and 600 million people use areca (also called betel) nut, one of the most popular psychoactive substances in the world after nicotine, alcohol, and caffeine. Smokeless tobacco products are consumed without burning and can be chewed, sucked, inhaled, applied locally, or ingested. Areca nut is the seed of the areca palm and can be consumed in various forms.
“Our estimates highlight the burden these products pose on health care and the importance of prevention strategies to reduce consumption of smokeless tobacco and areca nut,” Rumgay said.
According to the new report, in 2022, an estimated 120,200 of the 389,800 (30.8%) global cases of oral cancer were attributable to these products.
More than three quarters (77%) of attributable cases were among men and about one quarter (23%) among women.
The vast majority (96%) of all oral cancer cases caused by smokeless tobacco and areca nut use occurred in low- and middle-income countries.
Regions with the highest burden of oral cancers from these products were Southcentral Asia — with 105,500 of 120,200 cases (nearly 88%), including 83,400 in India, 9700 in Bangladesh, 8900 in Pakistan, and 1300 in Sri Lanka — followed by Southeastern Asia with a total of 3900 cases (1600 in Myanmar, 990 in Indonesia, and 785 in Thailand) and East Asia with 3300 cases (3200 in China).
Limitations and Action Points
The authors noted a limitation of the analysis is not accounting for the potential synergistic effects of combined use of smokeless tobacco or areca nut products with other risk factors for oral cancer, such as smoking tobacco or drinking alcohol.
The researchers explained that combined consumption of smokeless tobacco or areca nut, smoked tobacco, and alcohol has a “multiplicative effect” on oral cancer risk, with reported odds ratios increasing from 2.7 for smokeless tobacco only, 7.0 for smoked tobacco only, and 1.6 for alcohol only to 16.2 for all three exposures (vs no use).
However, the proportion of people who chewed tobacco and also smoked in countries with high smokeless tobacco or areca nut use was small. In India, for example, 6% of men and 0.5% of women in 2016-2017 were dual users of both smoked and smokeless tobacco, compared with 23% of men and 12% of women who only used smokeless tobacco.
Overall, curbing or preventing smokeless tobacco and areca nut use could help avoid many instances of oral cancer.
Despite “encouraging trends” in control of tobacco smoking in many regions of the world over the past two decades, progress in reducing the prevalence of smokeless tobacco consumption has stalled in many countries that are major consumers, the authors said.
Compounding the problem, areca nut does not fall within the WHO framework of tobacco control and there are very few areca nut control policies worldwide.
Smokeless tobacco control must be “prioritized” and a framework on areca nut control should be developed with guidelines to incorporate areca nut prevention into cancer control programs, the authors concluded.
Funding for the study was provided by the French National Cancer Institute. The authors had no relevant disclosures.
A version of this article first appeared on Medscape.com.
“Smokeless tobacco and areca nut products are available to consumers in many different forms across the world, but consuming smokeless tobacco and areca nut is linked to multiple diseases, including oral cancer,” Harriet Rumgay, PhD, a scientist in the Cancer Surveillance Branch at IARC and first author of the study in Lancet Oncology, said in a news release.
Worldwide, about 300 million people use smokeless tobacco and 600 million people use areca (also called betel) nut, one of the most popular psychoactive substances in the world after nicotine, alcohol, and caffeine. Smokeless tobacco products are consumed without burning and can be chewed, sucked, inhaled, applied locally, or ingested. Areca nut is the seed of the areca palm and can be consumed in various forms.
“Our estimates highlight the burden these products pose on health care and the importance of prevention strategies to reduce consumption of smokeless tobacco and areca nut,” Rumgay said.
According to the new report, in 2022, an estimated 120,200 of the 389,800 (30.8%) global cases of oral cancer were attributable to these products.
More than three quarters (77%) of attributable cases were among men and about one quarter (23%) among women.
The vast majority (96%) of all oral cancer cases caused by smokeless tobacco and areca nut use occurred in low- and middle-income countries.
Regions with the highest burden of oral cancers from these products were Southcentral Asia — with 105,500 of 120,200 cases (nearly 88%), including 83,400 in India, 9700 in Bangladesh, 8900 in Pakistan, and 1300 in Sri Lanka — followed by Southeastern Asia with a total of 3900 cases (1600 in Myanmar, 990 in Indonesia, and 785 in Thailand) and East Asia with 3300 cases (3200 in China).
Limitations and Action Points
The authors noted a limitation of the analysis is not accounting for the potential synergistic effects of combined use of smokeless tobacco or areca nut products with other risk factors for oral cancer, such as smoking tobacco or drinking alcohol.
The researchers explained that combined consumption of smokeless tobacco or areca nut, smoked tobacco, and alcohol has a “multiplicative effect” on oral cancer risk, with reported odds ratios increasing from 2.7 for smokeless tobacco only, 7.0 for smoked tobacco only, and 1.6 for alcohol only to 16.2 for all three exposures (vs no use).
However, the proportion of people who chewed tobacco and also smoked in countries with high smokeless tobacco or areca nut use was small. In India, for example, 6% of men and 0.5% of women in 2016-2017 were dual users of both smoked and smokeless tobacco, compared with 23% of men and 12% of women who only used smokeless tobacco.
Overall, curbing or preventing smokeless tobacco and areca nut use could help avoid many instances of oral cancer.
Despite “encouraging trends” in control of tobacco smoking in many regions of the world over the past two decades, progress in reducing the prevalence of smokeless tobacco consumption has stalled in many countries that are major consumers, the authors said.
Compounding the problem, areca nut does not fall within the WHO framework of tobacco control and there are very few areca nut control policies worldwide.
Smokeless tobacco control must be “prioritized” and a framework on areca nut control should be developed with guidelines to incorporate areca nut prevention into cancer control programs, the authors concluded.
Funding for the study was provided by the French National Cancer Institute. The authors had no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM THE LANCET ONCOLOGY