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Phase 3 shows promising activity of capivasertib-fulvestrant combo in HR+/HER2− advanced BC
Key clinical point: Capivasertib-fulvestrant therapy demonstrated significant progression-free survival (PFS) benefit and a manageable safety profile in patients with endocrine therapy-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).
Major finding: Significant PFS benefits were observed with capivasertib+fulvestrant vs placebo+fulvestrant in the overall population (hazard ratio for progression or death 0.60; P < .001) and in patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors (hazard ratio 0.50; P < .001). Diarrhea and rash were the most common adverse events in the capivasertib+fulvestrant group.
Study details: Findings are from a primary analysis of the phase 3 CAPItello-291 study including 708 patients with HR+/HER2− advanced BC who had progressed on an aromatase inhibitor with or without cyclin-dependent kinase 4 and 6 inhibitor and were randomly assigned to receive fulvestrant with capivasertib or placebo.
Disclosures: This study was supported by AstraZeneca and other sources. Four authors declared being employees and stockholders in AstraZeneca. Some authors declared having ties with several sources.
Source: Turner NC et al for the CAPItello-291 Study Group. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med. 2023;388(22):2058-2070 (Jun 1). doi: 10.1056/NEJMoa2214131
Key clinical point: Capivasertib-fulvestrant therapy demonstrated significant progression-free survival (PFS) benefit and a manageable safety profile in patients with endocrine therapy-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).
Major finding: Significant PFS benefits were observed with capivasertib+fulvestrant vs placebo+fulvestrant in the overall population (hazard ratio for progression or death 0.60; P < .001) and in patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors (hazard ratio 0.50; P < .001). Diarrhea and rash were the most common adverse events in the capivasertib+fulvestrant group.
Study details: Findings are from a primary analysis of the phase 3 CAPItello-291 study including 708 patients with HR+/HER2− advanced BC who had progressed on an aromatase inhibitor with or without cyclin-dependent kinase 4 and 6 inhibitor and were randomly assigned to receive fulvestrant with capivasertib or placebo.
Disclosures: This study was supported by AstraZeneca and other sources. Four authors declared being employees and stockholders in AstraZeneca. Some authors declared having ties with several sources.
Source: Turner NC et al for the CAPItello-291 Study Group. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med. 2023;388(22):2058-2070 (Jun 1). doi: 10.1056/NEJMoa2214131
Key clinical point: Capivasertib-fulvestrant therapy demonstrated significant progression-free survival (PFS) benefit and a manageable safety profile in patients with endocrine therapy-resistant hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).
Major finding: Significant PFS benefits were observed with capivasertib+fulvestrant vs placebo+fulvestrant in the overall population (hazard ratio for progression or death 0.60; P < .001) and in patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors (hazard ratio 0.50; P < .001). Diarrhea and rash were the most common adverse events in the capivasertib+fulvestrant group.
Study details: Findings are from a primary analysis of the phase 3 CAPItello-291 study including 708 patients with HR+/HER2− advanced BC who had progressed on an aromatase inhibitor with or without cyclin-dependent kinase 4 and 6 inhibitor and were randomly assigned to receive fulvestrant with capivasertib or placebo.
Disclosures: This study was supported by AstraZeneca and other sources. Four authors declared being employees and stockholders in AstraZeneca. Some authors declared having ties with several sources.
Source: Turner NC et al for the CAPItello-291 Study Group. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med. 2023;388(22):2058-2070 (Jun 1). doi: 10.1056/NEJMoa2214131
Atopic dermatitis shortens biologic-free survival in inflammatory bowel disease
Key clinical point: Presence of concurrent atopic dermatitis (AD) significantly affects the biologic-free survival in patients with inflammatory bowel disease (IBD).
Major finding: Presence of concurrent AD was associated with a significantly shorter biologic-free survival in patients with IBD (adjusted hazard ratio [aHR] 1.743; P = .032), with the association being stronger in patients with ulcerative colitis (aHR 4.769; P = .004).
Study details: Findings are from a retrospective study including 61 adult patients with IBD and concurrent AD and 122 matched control individuals with IBD alone.
Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korea government and others. The authors declared no conflicts of interest.
Source: Kim KW, et al, and Seoul National University Inflammatory Bowel Disease Research Network (SIRN) and Inflammatory Bowel Disease Research Group of Korean Association for the Study of Intestinal Disease (KASID). Atopic dermatitis is associated with the clinical course of inflammatory bowel disease. Scand J Gastroenterol. 2023;1-7 (May 11). doi: 10.1080/00365521.2023.2209688
Key clinical point: Presence of concurrent atopic dermatitis (AD) significantly affects the biologic-free survival in patients with inflammatory bowel disease (IBD).
Major finding: Presence of concurrent AD was associated with a significantly shorter biologic-free survival in patients with IBD (adjusted hazard ratio [aHR] 1.743; P = .032), with the association being stronger in patients with ulcerative colitis (aHR 4.769; P = .004).
Study details: Findings are from a retrospective study including 61 adult patients with IBD and concurrent AD and 122 matched control individuals with IBD alone.
Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korea government and others. The authors declared no conflicts of interest.
Source: Kim KW, et al, and Seoul National University Inflammatory Bowel Disease Research Network (SIRN) and Inflammatory Bowel Disease Research Group of Korean Association for the Study of Intestinal Disease (KASID). Atopic dermatitis is associated with the clinical course of inflammatory bowel disease. Scand J Gastroenterol. 2023;1-7 (May 11). doi: 10.1080/00365521.2023.2209688
Key clinical point: Presence of concurrent atopic dermatitis (AD) significantly affects the biologic-free survival in patients with inflammatory bowel disease (IBD).
Major finding: Presence of concurrent AD was associated with a significantly shorter biologic-free survival in patients with IBD (adjusted hazard ratio [aHR] 1.743; P = .032), with the association being stronger in patients with ulcerative colitis (aHR 4.769; P = .004).
Study details: Findings are from a retrospective study including 61 adult patients with IBD and concurrent AD and 122 matched control individuals with IBD alone.
Disclosures: This study was supported by the National Research Foundation of Korea grant funded by the Korea government and others. The authors declared no conflicts of interest.
Source: Kim KW, et al, and Seoul National University Inflammatory Bowel Disease Research Network (SIRN) and Inflammatory Bowel Disease Research Group of Korean Association for the Study of Intestinal Disease (KASID). Atopic dermatitis is associated with the clinical course of inflammatory bowel disease. Scand J Gastroenterol. 2023;1-7 (May 11). doi: 10.1080/00365521.2023.2209688
Dupilumab ameliorates disease signs and symptoms in children with severe atopic dermatitis
Key clinical point: Dupilumab significantly improves disease signs and symptoms in children with severe atopic dermatitis (AD), including those not achieving a clear or almost clear skin by week 16.
Major finding: At week 16, a significantly higher proportion of children in the dupilumab 200 mg+topical corticosteroid (TCS) and dupilumab 300 mg+TCS vs placebo+TCS groups achieved a ≥50% improvement in the Eczema Area and Severity Index score (both P < .0001), with patients in both treatment groups with an Investigator’s Global Assessment score of >1 also showing significant improvements (P = .0002 and P < .0001, respectively). No new safety signals were reported.
Study details: This post hoc analysis of LIBERTY AD PEDS trial included 304 children age 6-11 years with severe AD who were randomly assigned to receive dupilumab 200 mg+TCS, dupilumab 300 mg+TCS, or placebo+TCS.
Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Some authors reported ties with Sanofi-Regeneron and others. Six authors declared being employees of or holding stock or stock options in Sanofi/Regeneron.
Source: Siegfried EC et al. Dupilumab provides clinically meaningful responses in children aged 6–11 years with severe atopic dermatitis: Post hoc analysis results from a phase III trial. Am J Clin Dermatol. 2023 (Jun 10). doi: 10.1007/s40257-023-00791-7
Key clinical point: Dupilumab significantly improves disease signs and symptoms in children with severe atopic dermatitis (AD), including those not achieving a clear or almost clear skin by week 16.
Major finding: At week 16, a significantly higher proportion of children in the dupilumab 200 mg+topical corticosteroid (TCS) and dupilumab 300 mg+TCS vs placebo+TCS groups achieved a ≥50% improvement in the Eczema Area and Severity Index score (both P < .0001), with patients in both treatment groups with an Investigator’s Global Assessment score of >1 also showing significant improvements (P = .0002 and P < .0001, respectively). No new safety signals were reported.
Study details: This post hoc analysis of LIBERTY AD PEDS trial included 304 children age 6-11 years with severe AD who were randomly assigned to receive dupilumab 200 mg+TCS, dupilumab 300 mg+TCS, or placebo+TCS.
Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Some authors reported ties with Sanofi-Regeneron and others. Six authors declared being employees of or holding stock or stock options in Sanofi/Regeneron.
Source: Siegfried EC et al. Dupilumab provides clinically meaningful responses in children aged 6–11 years with severe atopic dermatitis: Post hoc analysis results from a phase III trial. Am J Clin Dermatol. 2023 (Jun 10). doi: 10.1007/s40257-023-00791-7
Key clinical point: Dupilumab significantly improves disease signs and symptoms in children with severe atopic dermatitis (AD), including those not achieving a clear or almost clear skin by week 16.
Major finding: At week 16, a significantly higher proportion of children in the dupilumab 200 mg+topical corticosteroid (TCS) and dupilumab 300 mg+TCS vs placebo+TCS groups achieved a ≥50% improvement in the Eczema Area and Severity Index score (both P < .0001), with patients in both treatment groups with an Investigator’s Global Assessment score of >1 also showing significant improvements (P = .0002 and P < .0001, respectively). No new safety signals were reported.
Study details: This post hoc analysis of LIBERTY AD PEDS trial included 304 children age 6-11 years with severe AD who were randomly assigned to receive dupilumab 200 mg+TCS, dupilumab 300 mg+TCS, or placebo+TCS.
Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Some authors reported ties with Sanofi-Regeneron and others. Six authors declared being employees of or holding stock or stock options in Sanofi/Regeneron.
Source: Siegfried EC et al. Dupilumab provides clinically meaningful responses in children aged 6–11 years with severe atopic dermatitis: Post hoc analysis results from a phase III trial. Am J Clin Dermatol. 2023 (Jun 10). doi: 10.1007/s40257-023-00791-7
Meta-analysis reveals that abrocitinib and upadacitinib top dupilumab in moderate-to-severe atopic dermatitis
Key clinical point: Abrocitinib and upadacitinib demonstrated acceptable safety profiles and provided greater improvements in disease signs and symptoms compared with dupilumab as early as week 2 in patients with moderate-to-severe atopic dermatitis (AD).
Major finding: A significantly higher proportion of patients in the abrocitinib/upadacitinib vs dupilumab group achieved a ≥75% improvement in Eczema Area and Severity Index scores and ≥4-point improvement in Peak Pruritus Numerical Rating Scale scores at 2 weeks (relative risk [RR] 1.92 and RR 1.87, respectively; both P < .001) and the end of therapy (RR 1.12; P = .002 and RR 1.20; P < .001, respectively). Although the severe adverse event rate was higher in the abrocitinib/upadacitinib vs dupilumab group (P = .043), the treatment-emergent adverse event rate leading to treatment discontinuation was similar.
Study details: This meta-analysis of three randomized controlled trials included 2256 patients with moderate-to-severe AD who received abrocitinib, upadacitinib, or dupilumab.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Gao Q et al. Efficacy and safety of abrocitinib and upadacitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: A systematic review and meta-analysis. Heliyon. 2023;9:E16704 (Jun 2). doi: 10.1016/j.heliyon.2023.e16704/p>
Key clinical point: Abrocitinib and upadacitinib demonstrated acceptable safety profiles and provided greater improvements in disease signs and symptoms compared with dupilumab as early as week 2 in patients with moderate-to-severe atopic dermatitis (AD).
Major finding: A significantly higher proportion of patients in the abrocitinib/upadacitinib vs dupilumab group achieved a ≥75% improvement in Eczema Area and Severity Index scores and ≥4-point improvement in Peak Pruritus Numerical Rating Scale scores at 2 weeks (relative risk [RR] 1.92 and RR 1.87, respectively; both P < .001) and the end of therapy (RR 1.12; P = .002 and RR 1.20; P < .001, respectively). Although the severe adverse event rate was higher in the abrocitinib/upadacitinib vs dupilumab group (P = .043), the treatment-emergent adverse event rate leading to treatment discontinuation was similar.
Study details: This meta-analysis of three randomized controlled trials included 2256 patients with moderate-to-severe AD who received abrocitinib, upadacitinib, or dupilumab.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Gao Q et al. Efficacy and safety of abrocitinib and upadacitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: A systematic review and meta-analysis. Heliyon. 2023;9:E16704 (Jun 2). doi: 10.1016/j.heliyon.2023.e16704/p>
Key clinical point: Abrocitinib and upadacitinib demonstrated acceptable safety profiles and provided greater improvements in disease signs and symptoms compared with dupilumab as early as week 2 in patients with moderate-to-severe atopic dermatitis (AD).
Major finding: A significantly higher proportion of patients in the abrocitinib/upadacitinib vs dupilumab group achieved a ≥75% improvement in Eczema Area and Severity Index scores and ≥4-point improvement in Peak Pruritus Numerical Rating Scale scores at 2 weeks (relative risk [RR] 1.92 and RR 1.87, respectively; both P < .001) and the end of therapy (RR 1.12; P = .002 and RR 1.20; P < .001, respectively). Although the severe adverse event rate was higher in the abrocitinib/upadacitinib vs dupilumab group (P = .043), the treatment-emergent adverse event rate leading to treatment discontinuation was similar.
Study details: This meta-analysis of three randomized controlled trials included 2256 patients with moderate-to-severe AD who received abrocitinib, upadacitinib, or dupilumab.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Gao Q et al. Efficacy and safety of abrocitinib and upadacitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: A systematic review and meta-analysis. Heliyon. 2023;9:E16704 (Jun 2). doi: 10.1016/j.heliyon.2023.e16704/p>
Early emollient use does not lower the odds of atopic dermatitis in high-risk infants
Key clinical point: Daily use of an emollient with a prebiotic lysate in the first year of life was safe but did not decrease the risk of developing atopic dermatitis (AD) in high-risk infants.
Major finding: At 2 years, the cumulative incidence of AD among infants receiving general skin care+emollient containing a prebiotic Vitreoscilla filiformis lysate (at least once daily until 1 year of age; intervention group) and general skin care (control group) was comparable (28% and 24%, respectively; adjusted relative risk 1.17; 95% CI 0.46-2.98). No emollient-related adverse events were reported.
Study details: Findings are from the randomized prospective EARLYEmollient study including 50 term-born infants aged 1-21 days with a high risk for AD who were randomly assigned to the intervention (n = 25) or control (n = 25) group.
Disclosures: This study was supported by La Roche-Posay Laboratoire Pharmaceutique, France. Some authors declared serving as lecturers or consultants, receiving institutional grants, or participating in advisory board meetings for various sources.
Source: Harder I et al. Effects of early emollient use in children at high risk of atopic dermatitis: A German pilot study. Acta Derm Venereol. 2023;103:adv5671 (May 29). doi: 10.2340/actadv.v103.5671
Key clinical point: Daily use of an emollient with a prebiotic lysate in the first year of life was safe but did not decrease the risk of developing atopic dermatitis (AD) in high-risk infants.
Major finding: At 2 years, the cumulative incidence of AD among infants receiving general skin care+emollient containing a prebiotic Vitreoscilla filiformis lysate (at least once daily until 1 year of age; intervention group) and general skin care (control group) was comparable (28% and 24%, respectively; adjusted relative risk 1.17; 95% CI 0.46-2.98). No emollient-related adverse events were reported.
Study details: Findings are from the randomized prospective EARLYEmollient study including 50 term-born infants aged 1-21 days with a high risk for AD who were randomly assigned to the intervention (n = 25) or control (n = 25) group.
Disclosures: This study was supported by La Roche-Posay Laboratoire Pharmaceutique, France. Some authors declared serving as lecturers or consultants, receiving institutional grants, or participating in advisory board meetings for various sources.
Source: Harder I et al. Effects of early emollient use in children at high risk of atopic dermatitis: A German pilot study. Acta Derm Venereol. 2023;103:adv5671 (May 29). doi: 10.2340/actadv.v103.5671
Key clinical point: Daily use of an emollient with a prebiotic lysate in the first year of life was safe but did not decrease the risk of developing atopic dermatitis (AD) in high-risk infants.
Major finding: At 2 years, the cumulative incidence of AD among infants receiving general skin care+emollient containing a prebiotic Vitreoscilla filiformis lysate (at least once daily until 1 year of age; intervention group) and general skin care (control group) was comparable (28% and 24%, respectively; adjusted relative risk 1.17; 95% CI 0.46-2.98). No emollient-related adverse events were reported.
Study details: Findings are from the randomized prospective EARLYEmollient study including 50 term-born infants aged 1-21 days with a high risk for AD who were randomly assigned to the intervention (n = 25) or control (n = 25) group.
Disclosures: This study was supported by La Roche-Posay Laboratoire Pharmaceutique, France. Some authors declared serving as lecturers or consultants, receiving institutional grants, or participating in advisory board meetings for various sources.
Source: Harder I et al. Effects of early emollient use in children at high risk of atopic dermatitis: A German pilot study. Acta Derm Venereol. 2023;103:adv5671 (May 29). doi: 10.2340/actadv.v103.5671
Electronic nose may sniff out early lung cancer in COPD
, based on data from a prospective study of approximately 800 individuals.
Lung cancer remains a major cause of death in patients with chronic obstructive pulmonary disease (COPD), but many cases may go undetected in the early stage because of lack of screening and lack of validated predictive biomarkers, wrote Rianne de Vries, PhD, of the University of Amsterdam, and colleagues.
Accurate, noninvasive tests to screen patients with COPD for lung cancer are needed, and molecular profiling of exhaled breath using electronic nose (eNose) technology has shown potential as a method of early detection by identifying patterns of exhaled volatile organic compounds (VOCs), they said.
In a study published in the journal Chest, the researchers reviewed data from 682 adults with COPD and 211 with lung cancer who were enrolled in BreathCloud, a multicenter, observational study of healthy controls and individuals with suspected or confirmed diagnosis of asthma, COPD, or lung cancer.
Patients’ breath profiles were collected at study enrollment, between May 2017 and November 2018, using a metal oxide semiconductor eNose (SpiroNose).
Data from the eNose included the highest sensor peak normalized to the most stable sensor and the ratio between sensor peak and breath hold point. These variables were combined into four principal components (PCs) that captured 78.4% of variance in the dataset, and training and validation sets were constructed for all subjects. The researchers calculated a receiver operating characteristic (ROC) curve, including the area under the curve (AUC).
All patients were treated with standard clinical care and were monitored for development of clinically diagnosed lung cancer for 2 years, confirmed via CT imaging. The mean age of the patients was 64 years, and demographics at baseline were similar for patients with and without lung cancer.
After exclusion of 116 patients with both COPD and lung cancer, the analysis showed an accuracy of 90% and a ROC-AUC of 0.95.
Within 2 years of study enrollment, 37 patients with COPD (5.4%) developed lung cancer. In training sets and validation sets, the principal components one, two, and three were significantly different in patients with COPD who developed lung cancer and those who did not, (P = .002, P < .001, P < .001, respectively). The ROC-AUCs of the testing and validation sets were 0.89 and 0.86, respectively.
“Interestingly, the VOC pattern associated with early development of lung cancer in COPD did not match to the pattern related to lung cancer stages, as the former was mainly captured by PC2 and the latter by PC3,” the researchers wrote in their discussion. “This suggests that early identification of upcoming clinically manifest lung cancer in patients with COPD by eNose is not driven by VOCs that are predominantly associated with a particular stage of the disease,” they said.
The findings were limited by several factors including the lack of CT scanning at baseline because of the real-world design, so the presence of any baseline tumors was unknown, although none of the COPD patients showed symptoms indicative of lung cancer at baseline, the researchers noted.
However, the results suggest that eNose technology can identify lung cancer-specific VOC patterns early in cancer development in COPD patients, which provides a possible opportunity for early intervention, they concluded.
The study received no outside funding. De Vries disclosed personal fees and a substantial interest in the start-up company Breathomix.
A version of this article first appeared on Medscape.com.
, based on data from a prospective study of approximately 800 individuals.
Lung cancer remains a major cause of death in patients with chronic obstructive pulmonary disease (COPD), but many cases may go undetected in the early stage because of lack of screening and lack of validated predictive biomarkers, wrote Rianne de Vries, PhD, of the University of Amsterdam, and colleagues.
Accurate, noninvasive tests to screen patients with COPD for lung cancer are needed, and molecular profiling of exhaled breath using electronic nose (eNose) technology has shown potential as a method of early detection by identifying patterns of exhaled volatile organic compounds (VOCs), they said.
In a study published in the journal Chest, the researchers reviewed data from 682 adults with COPD and 211 with lung cancer who were enrolled in BreathCloud, a multicenter, observational study of healthy controls and individuals with suspected or confirmed diagnosis of asthma, COPD, or lung cancer.
Patients’ breath profiles were collected at study enrollment, between May 2017 and November 2018, using a metal oxide semiconductor eNose (SpiroNose).
Data from the eNose included the highest sensor peak normalized to the most stable sensor and the ratio between sensor peak and breath hold point. These variables were combined into four principal components (PCs) that captured 78.4% of variance in the dataset, and training and validation sets were constructed for all subjects. The researchers calculated a receiver operating characteristic (ROC) curve, including the area under the curve (AUC).
All patients were treated with standard clinical care and were monitored for development of clinically diagnosed lung cancer for 2 years, confirmed via CT imaging. The mean age of the patients was 64 years, and demographics at baseline were similar for patients with and without lung cancer.
After exclusion of 116 patients with both COPD and lung cancer, the analysis showed an accuracy of 90% and a ROC-AUC of 0.95.
Within 2 years of study enrollment, 37 patients with COPD (5.4%) developed lung cancer. In training sets and validation sets, the principal components one, two, and three were significantly different in patients with COPD who developed lung cancer and those who did not, (P = .002, P < .001, P < .001, respectively). The ROC-AUCs of the testing and validation sets were 0.89 and 0.86, respectively.
“Interestingly, the VOC pattern associated with early development of lung cancer in COPD did not match to the pattern related to lung cancer stages, as the former was mainly captured by PC2 and the latter by PC3,” the researchers wrote in their discussion. “This suggests that early identification of upcoming clinically manifest lung cancer in patients with COPD by eNose is not driven by VOCs that are predominantly associated with a particular stage of the disease,” they said.
The findings were limited by several factors including the lack of CT scanning at baseline because of the real-world design, so the presence of any baseline tumors was unknown, although none of the COPD patients showed symptoms indicative of lung cancer at baseline, the researchers noted.
However, the results suggest that eNose technology can identify lung cancer-specific VOC patterns early in cancer development in COPD patients, which provides a possible opportunity for early intervention, they concluded.
The study received no outside funding. De Vries disclosed personal fees and a substantial interest in the start-up company Breathomix.
A version of this article first appeared on Medscape.com.
, based on data from a prospective study of approximately 800 individuals.
Lung cancer remains a major cause of death in patients with chronic obstructive pulmonary disease (COPD), but many cases may go undetected in the early stage because of lack of screening and lack of validated predictive biomarkers, wrote Rianne de Vries, PhD, of the University of Amsterdam, and colleagues.
Accurate, noninvasive tests to screen patients with COPD for lung cancer are needed, and molecular profiling of exhaled breath using electronic nose (eNose) technology has shown potential as a method of early detection by identifying patterns of exhaled volatile organic compounds (VOCs), they said.
In a study published in the journal Chest, the researchers reviewed data from 682 adults with COPD and 211 with lung cancer who were enrolled in BreathCloud, a multicenter, observational study of healthy controls and individuals with suspected or confirmed diagnosis of asthma, COPD, or lung cancer.
Patients’ breath profiles were collected at study enrollment, between May 2017 and November 2018, using a metal oxide semiconductor eNose (SpiroNose).
Data from the eNose included the highest sensor peak normalized to the most stable sensor and the ratio between sensor peak and breath hold point. These variables were combined into four principal components (PCs) that captured 78.4% of variance in the dataset, and training and validation sets were constructed for all subjects. The researchers calculated a receiver operating characteristic (ROC) curve, including the area under the curve (AUC).
All patients were treated with standard clinical care and were monitored for development of clinically diagnosed lung cancer for 2 years, confirmed via CT imaging. The mean age of the patients was 64 years, and demographics at baseline were similar for patients with and without lung cancer.
After exclusion of 116 patients with both COPD and lung cancer, the analysis showed an accuracy of 90% and a ROC-AUC of 0.95.
Within 2 years of study enrollment, 37 patients with COPD (5.4%) developed lung cancer. In training sets and validation sets, the principal components one, two, and three were significantly different in patients with COPD who developed lung cancer and those who did not, (P = .002, P < .001, P < .001, respectively). The ROC-AUCs of the testing and validation sets were 0.89 and 0.86, respectively.
“Interestingly, the VOC pattern associated with early development of lung cancer in COPD did not match to the pattern related to lung cancer stages, as the former was mainly captured by PC2 and the latter by PC3,” the researchers wrote in their discussion. “This suggests that early identification of upcoming clinically manifest lung cancer in patients with COPD by eNose is not driven by VOCs that are predominantly associated with a particular stage of the disease,” they said.
The findings were limited by several factors including the lack of CT scanning at baseline because of the real-world design, so the presence of any baseline tumors was unknown, although none of the COPD patients showed symptoms indicative of lung cancer at baseline, the researchers noted.
However, the results suggest that eNose technology can identify lung cancer-specific VOC patterns early in cancer development in COPD patients, which provides a possible opportunity for early intervention, they concluded.
The study received no outside funding. De Vries disclosed personal fees and a substantial interest in the start-up company Breathomix.
A version of this article first appeared on Medscape.com.
FROM CHEST
Abrocitinib improves outcomes in severe or difficult-to-treat atopic dermatitis
Key clinical point: Abrocitinib led to greater and rapid improvements in itch and skin clearance compared with placebo in patients with severe or difficult-to-treat atopic dermatitis (AD).
Major finding: At week 16, a significantly higher proportion of patients achieved an Investigator’s Global Assessment score of 0 or 1, Eczema Area and Severity Index-75 and -90 responses, and a ≥4-point improvement in Peak Pruritus Numerical Rating Scale score with abrocitinib 200-mg vs placebo across all subgroups (all nominal P < .05).
Study details: This post hoc analysis of the JADE COMPARE trial (n = 837) included a subset of patients with severe or difficult-to-treat AD who were randomly assigned to receive oral abrocitinib (200 or 100 mg), subcutaneous dupilumab (300 mg), or placebo with medicated topical therapy for 16 weeks.
Disclosures: This study was funded by Pfizer Inc. Some authors declared receiving grants or personal fees or serving as consultants, speakers, board members, or investigators for various organizations, including Pfizer. Five authors declared being employees of or shareholders in Pfizer.
Source: Simpson EL et al. Efficacy and safety of abrocitinib in patients with severe and/or difficult‑to‑treat atopic dermatitis: A post hoc analysis of the randomized phase 3 JADE COMPARE trial. Am J Clin Dermatol. 2023 (May 22). doi: 10.1007/s40257-023-00785-5
Key clinical point: Abrocitinib led to greater and rapid improvements in itch and skin clearance compared with placebo in patients with severe or difficult-to-treat atopic dermatitis (AD).
Major finding: At week 16, a significantly higher proportion of patients achieved an Investigator’s Global Assessment score of 0 or 1, Eczema Area and Severity Index-75 and -90 responses, and a ≥4-point improvement in Peak Pruritus Numerical Rating Scale score with abrocitinib 200-mg vs placebo across all subgroups (all nominal P < .05).
Study details: This post hoc analysis of the JADE COMPARE trial (n = 837) included a subset of patients with severe or difficult-to-treat AD who were randomly assigned to receive oral abrocitinib (200 or 100 mg), subcutaneous dupilumab (300 mg), or placebo with medicated topical therapy for 16 weeks.
Disclosures: This study was funded by Pfizer Inc. Some authors declared receiving grants or personal fees or serving as consultants, speakers, board members, or investigators for various organizations, including Pfizer. Five authors declared being employees of or shareholders in Pfizer.
Source: Simpson EL et al. Efficacy and safety of abrocitinib in patients with severe and/or difficult‑to‑treat atopic dermatitis: A post hoc analysis of the randomized phase 3 JADE COMPARE trial. Am J Clin Dermatol. 2023 (May 22). doi: 10.1007/s40257-023-00785-5
Key clinical point: Abrocitinib led to greater and rapid improvements in itch and skin clearance compared with placebo in patients with severe or difficult-to-treat atopic dermatitis (AD).
Major finding: At week 16, a significantly higher proportion of patients achieved an Investigator’s Global Assessment score of 0 or 1, Eczema Area and Severity Index-75 and -90 responses, and a ≥4-point improvement in Peak Pruritus Numerical Rating Scale score with abrocitinib 200-mg vs placebo across all subgroups (all nominal P < .05).
Study details: This post hoc analysis of the JADE COMPARE trial (n = 837) included a subset of patients with severe or difficult-to-treat AD who were randomly assigned to receive oral abrocitinib (200 or 100 mg), subcutaneous dupilumab (300 mg), or placebo with medicated topical therapy for 16 weeks.
Disclosures: This study was funded by Pfizer Inc. Some authors declared receiving grants or personal fees or serving as consultants, speakers, board members, or investigators for various organizations, including Pfizer. Five authors declared being employees of or shareholders in Pfizer.
Source: Simpson EL et al. Efficacy and safety of abrocitinib in patients with severe and/or difficult‑to‑treat atopic dermatitis: A post hoc analysis of the randomized phase 3 JADE COMPARE trial. Am J Clin Dermatol. 2023 (May 22). doi: 10.1007/s40257-023-00785-5
Successful dupilumab dose tapering in controlled atopic dermatitis
Key clinical point: Dupilumab dose was successfully tapered while maintaining controlled disease in the majority of patients with atopic dermatitis (AD) using a patient-centered dosing regimen in a large daily practice cohort study.
Major finding: Dose reduction was successful in 83.3% of patients who prolonged dupilumab interval while maintaining controlled disease, with most patients receiving dupilumab every 3 or 4 weeks. Although a significant small increase was observed in the highest mean Eczema Area and Severity Index and Numeric Rating Scale-Pruritis scores (both P < .001), the scores remained low.
Study details: Findings are from a prospective, multicenter study including 595 adult patients with controlled AD treated with dupilumab for ≥1 yearfrom the BioDay registry, of which 401 patients prolonged the dupilumab interval.
Disclosures: The BioDay registry was sponsored by Sanofi, AbbVie, and others. Some authors declared serving as investigators, speakers, advisors, or consultants for various sources, including the BioDay registry sponsors.
Source: Spekhorst LS, Boesjes CM, et al. Successful tapering of dupilumab in atopic dermatitis patients with low disease activity: A large pragmatic daily practice study from the BioDay registry. Br J Dermatol. 2023 (May 13). doi: 10.1093/bjd/ljad159
Key clinical point: Dupilumab dose was successfully tapered while maintaining controlled disease in the majority of patients with atopic dermatitis (AD) using a patient-centered dosing regimen in a large daily practice cohort study.
Major finding: Dose reduction was successful in 83.3% of patients who prolonged dupilumab interval while maintaining controlled disease, with most patients receiving dupilumab every 3 or 4 weeks. Although a significant small increase was observed in the highest mean Eczema Area and Severity Index and Numeric Rating Scale-Pruritis scores (both P < .001), the scores remained low.
Study details: Findings are from a prospective, multicenter study including 595 adult patients with controlled AD treated with dupilumab for ≥1 yearfrom the BioDay registry, of which 401 patients prolonged the dupilumab interval.
Disclosures: The BioDay registry was sponsored by Sanofi, AbbVie, and others. Some authors declared serving as investigators, speakers, advisors, or consultants for various sources, including the BioDay registry sponsors.
Source: Spekhorst LS, Boesjes CM, et al. Successful tapering of dupilumab in atopic dermatitis patients with low disease activity: A large pragmatic daily practice study from the BioDay registry. Br J Dermatol. 2023 (May 13). doi: 10.1093/bjd/ljad159
Key clinical point: Dupilumab dose was successfully tapered while maintaining controlled disease in the majority of patients with atopic dermatitis (AD) using a patient-centered dosing regimen in a large daily practice cohort study.
Major finding: Dose reduction was successful in 83.3% of patients who prolonged dupilumab interval while maintaining controlled disease, with most patients receiving dupilumab every 3 or 4 weeks. Although a significant small increase was observed in the highest mean Eczema Area and Severity Index and Numeric Rating Scale-Pruritis scores (both P < .001), the scores remained low.
Study details: Findings are from a prospective, multicenter study including 595 adult patients with controlled AD treated with dupilumab for ≥1 yearfrom the BioDay registry, of which 401 patients prolonged the dupilumab interval.
Disclosures: The BioDay registry was sponsored by Sanofi, AbbVie, and others. Some authors declared serving as investigators, speakers, advisors, or consultants for various sources, including the BioDay registry sponsors.
Source: Spekhorst LS, Boesjes CM, et al. Successful tapering of dupilumab in atopic dermatitis patients with low disease activity: A large pragmatic daily practice study from the BioDay registry. Br J Dermatol. 2023 (May 13). doi: 10.1093/bjd/ljad159
Switching to upadacitinib from dupilumab improves atopic dermatitis
Key clinical point: In patients with moderate-to-severe atopic dermatitis (AD), continuous upadacitinib treatment was safe and provided sustained responses through 40 weeks and switch to upadacitinib treatment improved outcomes irrespective of prior dupilumab response.
Major finding: At open-label extension week 16 vs Heads Up week 24, the mean Eczema Area and Severity Index scores were similar with continuous upadacitinib treatment (2.7 vs 2.6) and improved with a switch to upadacitinib from dupilumab (1.09 vs 3.29). Most patients without minimal threshold or adequate response with dupilumab achieved it with upadacitinib. No new safety signals were reported.
Study details: This 16-week interim analysis of a 52-week open-label extension study of the Heads Up trial included adults with moderate-to-severe AD who were assigned to continue receiving upadacitinib (n = 239) or switch to upadacitinib after 24 weeks of dupilumab (n = 245).
Disclosures: This study was supported by AbbVie Inc. Some authors reported ties with various organizations, including AbbVie. Eight authors declared being employees of or holding stock or stock options in AbbVie.
Source: Blauvelt A et al. Efficacy and safety of switching from dupilumab to upadacitinib versus continuous upadacitinib in moderate-to-severe atopic dermatitis: Results from an open-label extension of the phase 3, randomized, controlled trial (Heads Up). J Am Acad Dermatol. 2023 (May 22). doi: 10.1016/j.jaad.2023.05.033
Key clinical point: In patients with moderate-to-severe atopic dermatitis (AD), continuous upadacitinib treatment was safe and provided sustained responses through 40 weeks and switch to upadacitinib treatment improved outcomes irrespective of prior dupilumab response.
Major finding: At open-label extension week 16 vs Heads Up week 24, the mean Eczema Area and Severity Index scores were similar with continuous upadacitinib treatment (2.7 vs 2.6) and improved with a switch to upadacitinib from dupilumab (1.09 vs 3.29). Most patients without minimal threshold or adequate response with dupilumab achieved it with upadacitinib. No new safety signals were reported.
Study details: This 16-week interim analysis of a 52-week open-label extension study of the Heads Up trial included adults with moderate-to-severe AD who were assigned to continue receiving upadacitinib (n = 239) or switch to upadacitinib after 24 weeks of dupilumab (n = 245).
Disclosures: This study was supported by AbbVie Inc. Some authors reported ties with various organizations, including AbbVie. Eight authors declared being employees of or holding stock or stock options in AbbVie.
Source: Blauvelt A et al. Efficacy and safety of switching from dupilumab to upadacitinib versus continuous upadacitinib in moderate-to-severe atopic dermatitis: Results from an open-label extension of the phase 3, randomized, controlled trial (Heads Up). J Am Acad Dermatol. 2023 (May 22). doi: 10.1016/j.jaad.2023.05.033
Key clinical point: In patients with moderate-to-severe atopic dermatitis (AD), continuous upadacitinib treatment was safe and provided sustained responses through 40 weeks and switch to upadacitinib treatment improved outcomes irrespective of prior dupilumab response.
Major finding: At open-label extension week 16 vs Heads Up week 24, the mean Eczema Area and Severity Index scores were similar with continuous upadacitinib treatment (2.7 vs 2.6) and improved with a switch to upadacitinib from dupilumab (1.09 vs 3.29). Most patients without minimal threshold or adequate response with dupilumab achieved it with upadacitinib. No new safety signals were reported.
Study details: This 16-week interim analysis of a 52-week open-label extension study of the Heads Up trial included adults with moderate-to-severe AD who were assigned to continue receiving upadacitinib (n = 239) or switch to upadacitinib after 24 weeks of dupilumab (n = 245).
Disclosures: This study was supported by AbbVie Inc. Some authors reported ties with various organizations, including AbbVie. Eight authors declared being employees of or holding stock or stock options in AbbVie.
Source: Blauvelt A et al. Efficacy and safety of switching from dupilumab to upadacitinib versus continuous upadacitinib in moderate-to-severe atopic dermatitis: Results from an open-label extension of the phase 3, randomized, controlled trial (Heads Up). J Am Acad Dermatol. 2023 (May 22). doi: 10.1016/j.jaad.2023.05.033
Crisaborole once daily an effective long-term maintenance therapy for atopic dermatitis
Key clinical point: Maintenance therapy with once-daily crisaborole is safe and effective in adult and pediatric patients with mild-to-moderate atopic dermatitis (AD) who have previously responded to twice-daily crisaborole treatment.
Major finding: The crisaborole vs vehicle group had a significantly longer median flare-free maintenance time (111 vs 30 days; P = .0034), higher mean number of flare-free days (234.0 vs 199.4 days; P = .0346), and lower mean number of flares (0.95 vs 1.36; P = .0042). No new safety signals were reported.
Study details: This phase 3 study (CrisADe CONTROL) included 270 patients age ≥3 months with mild-to-moderate AD who received twice-daily crisaborole for a maximum of 8 weeks; the responders were randomly assigned to receive once-daily crisaborole 2% ointment (n = 135) or vehicle (n = 135) for 52 weeks.
Disclosures: This study was funded by Pfizer Inc. Some authors declared serving as investigators, speakers, or consultants for or receiving research grants from various sources, including Pfizer. Six authors declared being employees of and shareholders in Pfizer.
Source: Eichenfield LF et al. Once‑daily crisaborole ointment, 2%, as a long‑term maintenance treatment in patients aged ≥ 3 months with mild‑to‑moderate atopic dermatitis: A 52-week clinical study. Am J Clin Dermatol. 2023 (May 15). doi: 10.1007/s40257-023-00780-w
Key clinical point: Maintenance therapy with once-daily crisaborole is safe and effective in adult and pediatric patients with mild-to-moderate atopic dermatitis (AD) who have previously responded to twice-daily crisaborole treatment.
Major finding: The crisaborole vs vehicle group had a significantly longer median flare-free maintenance time (111 vs 30 days; P = .0034), higher mean number of flare-free days (234.0 vs 199.4 days; P = .0346), and lower mean number of flares (0.95 vs 1.36; P = .0042). No new safety signals were reported.
Study details: This phase 3 study (CrisADe CONTROL) included 270 patients age ≥3 months with mild-to-moderate AD who received twice-daily crisaborole for a maximum of 8 weeks; the responders were randomly assigned to receive once-daily crisaborole 2% ointment (n = 135) or vehicle (n = 135) for 52 weeks.
Disclosures: This study was funded by Pfizer Inc. Some authors declared serving as investigators, speakers, or consultants for or receiving research grants from various sources, including Pfizer. Six authors declared being employees of and shareholders in Pfizer.
Source: Eichenfield LF et al. Once‑daily crisaborole ointment, 2%, as a long‑term maintenance treatment in patients aged ≥ 3 months with mild‑to‑moderate atopic dermatitis: A 52-week clinical study. Am J Clin Dermatol. 2023 (May 15). doi: 10.1007/s40257-023-00780-w
Key clinical point: Maintenance therapy with once-daily crisaborole is safe and effective in adult and pediatric patients with mild-to-moderate atopic dermatitis (AD) who have previously responded to twice-daily crisaborole treatment.
Major finding: The crisaborole vs vehicle group had a significantly longer median flare-free maintenance time (111 vs 30 days; P = .0034), higher mean number of flare-free days (234.0 vs 199.4 days; P = .0346), and lower mean number of flares (0.95 vs 1.36; P = .0042). No new safety signals were reported.
Study details: This phase 3 study (CrisADe CONTROL) included 270 patients age ≥3 months with mild-to-moderate AD who received twice-daily crisaborole for a maximum of 8 weeks; the responders were randomly assigned to receive once-daily crisaborole 2% ointment (n = 135) or vehicle (n = 135) for 52 weeks.
Disclosures: This study was funded by Pfizer Inc. Some authors declared serving as investigators, speakers, or consultants for or receiving research grants from various sources, including Pfizer. Six authors declared being employees of and shareholders in Pfizer.
Source: Eichenfield LF et al. Once‑daily crisaborole ointment, 2%, as a long‑term maintenance treatment in patients aged ≥ 3 months with mild‑to‑moderate atopic dermatitis: A 52-week clinical study. Am J Clin Dermatol. 2023 (May 15). doi: 10.1007/s40257-023-00780-w