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PI3K inhibitor/fulvestrant has modest benefit, serious toxicity in breast cancer
CHICAGO – Is two months of progression-free survival worth it if those months mean living with serious side effects?
For women with advanced estrogen receptor-positive, HER2-negative breast cancer, the combination of the PI3K inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) bought two additional months of PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half the patients treated with the combination, results of the SANDPIPER trial show.
“These results are positive, but I think we all agree they are modest,” lead investigator José Baselga, MD, PhD from Memorial Sloan Kettering Cancer Center in New York, said at a briefing at the annual meeting of the American Society of Clinical Oncology.
The “challenging tolerability” of the combination led to frequent treatment discontinuations, and may have limited the clinical benefit of the combination, he said, but added that the study serves as proof of principle that PI3K may be a bona fide target in advanced breast cancer.
ASCO expert Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston agreed that PI3K “is a very appealing target. It’s a mutation that probably is the most common in breast cancer when you do genomic sequencing, and it arises in other tumors as well.”
He likened the study findings, however, to a key opening a locked door, only to find that there is a chain latch on the other side preventing entry.
In an interview, Dr. Burstein said that despite the best efforts of Dr. Baselga and others to find a suitable approach to targeting the PI3K pathway, the evidence to date suggests that it may not be an important driver of breast cancer.
Taselisib is the first agent in its class to specifically block the PI3K alpha isoform that is found to be mutated in approximately 40% of advanced ER-positive breast cancer. The agent has been shown to offer clinical benefits in early trials for patients with head and neck and some gynecologic cancers.
In the phase 3 SANDPIPER trial, 516 women with locally advanced or metastatic ER-positive, HER2-negative breast cancer that had progressed or recurred following aromatase inhibitor therapy were enrolled and randomly assigned on a 2:1 basis to receive fulvestrant plus taselisib (340 patients) or fulvestrant plus a placebo (176 patients).
As noted, the median progression-free survival was 7.4 months for women who received the combination, compared with 5.4 months for controls. The stratified hazard ratio was 0.70 favoring taselisib (P = .0037).
But also as noted, the addition of taselisib “clearly led to toxicity,” Dr. Baselga said.
Serious adverse events occurred in 32% of patients in the fulvestrant/taselisib group, compared with 8.9% of controls. Grade 3 or greater side effects occurred in 49.5% vs. 16.4%, respectively, and side effects leading to discontinuation of taselisib occurred in 16.8% of patients, vs. 2.3% of those on placebo.
The primary toxicities were gastrointestinal effects, especially diarrhea, which occurred in 60.1% vs. 19.7% of patients (all grades). Hyperglycemia occurred in 40.4% of patients on taselisib, vs. 9.4% on placebo.
Dr. Baselga noted that the secondary endpoints of overall response rate, clinical benefit rate, and duration of response all favored taselisib.
Asked whether taselisib was the right agent in this setting, given the commercial availability of at least two other PI3K inhibitors – idelalisib (Zydelig) and copanlisib (Aliqopa) – Dr. Baselga agreed that another, more specific agent may offer similar or better efficacy with fewer off-target effects. He noted that taselisib is highly active against the alpha isoforms of PI3K, but also hits the delta and gamma isoforms.
“The side effects that we see that are limiting patients staying on [taselisib] are mostly delta and gamma. So I do think that in the case of breast cancer, what we need to do is to work on more specific alpha inhibitors that will be safer,” he said.
During the oral abstracts session where Dr. Baselga presented the SANDPIPER results, Cynthia X Ma, MD, PhD, from Washington University School of Medicine in St. Louis, the invited discussant, agreed that the trial provides proof of concept that PI3K inhibition may be an effective therapeutic strategy in breast cancer.
“However, the modest progression-free survival improvement and significant toxicity profile does not support its clinical application,” she said.
SOURCE: : Baselga J et al. ASCO 2018 Abstract LBA1006 .
CHICAGO – Is two months of progression-free survival worth it if those months mean living with serious side effects?
For women with advanced estrogen receptor-positive, HER2-negative breast cancer, the combination of the PI3K inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) bought two additional months of PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half the patients treated with the combination, results of the SANDPIPER trial show.
“These results are positive, but I think we all agree they are modest,” lead investigator José Baselga, MD, PhD from Memorial Sloan Kettering Cancer Center in New York, said at a briefing at the annual meeting of the American Society of Clinical Oncology.
The “challenging tolerability” of the combination led to frequent treatment discontinuations, and may have limited the clinical benefit of the combination, he said, but added that the study serves as proof of principle that PI3K may be a bona fide target in advanced breast cancer.
ASCO expert Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston agreed that PI3K “is a very appealing target. It’s a mutation that probably is the most common in breast cancer when you do genomic sequencing, and it arises in other tumors as well.”
He likened the study findings, however, to a key opening a locked door, only to find that there is a chain latch on the other side preventing entry.
In an interview, Dr. Burstein said that despite the best efforts of Dr. Baselga and others to find a suitable approach to targeting the PI3K pathway, the evidence to date suggests that it may not be an important driver of breast cancer.
Taselisib is the first agent in its class to specifically block the PI3K alpha isoform that is found to be mutated in approximately 40% of advanced ER-positive breast cancer. The agent has been shown to offer clinical benefits in early trials for patients with head and neck and some gynecologic cancers.
In the phase 3 SANDPIPER trial, 516 women with locally advanced or metastatic ER-positive, HER2-negative breast cancer that had progressed or recurred following aromatase inhibitor therapy were enrolled and randomly assigned on a 2:1 basis to receive fulvestrant plus taselisib (340 patients) or fulvestrant plus a placebo (176 patients).
As noted, the median progression-free survival was 7.4 months for women who received the combination, compared with 5.4 months for controls. The stratified hazard ratio was 0.70 favoring taselisib (P = .0037).
But also as noted, the addition of taselisib “clearly led to toxicity,” Dr. Baselga said.
Serious adverse events occurred in 32% of patients in the fulvestrant/taselisib group, compared with 8.9% of controls. Grade 3 or greater side effects occurred in 49.5% vs. 16.4%, respectively, and side effects leading to discontinuation of taselisib occurred in 16.8% of patients, vs. 2.3% of those on placebo.
The primary toxicities were gastrointestinal effects, especially diarrhea, which occurred in 60.1% vs. 19.7% of patients (all grades). Hyperglycemia occurred in 40.4% of patients on taselisib, vs. 9.4% on placebo.
Dr. Baselga noted that the secondary endpoints of overall response rate, clinical benefit rate, and duration of response all favored taselisib.
Asked whether taselisib was the right agent in this setting, given the commercial availability of at least two other PI3K inhibitors – idelalisib (Zydelig) and copanlisib (Aliqopa) – Dr. Baselga agreed that another, more specific agent may offer similar or better efficacy with fewer off-target effects. He noted that taselisib is highly active against the alpha isoforms of PI3K, but also hits the delta and gamma isoforms.
“The side effects that we see that are limiting patients staying on [taselisib] are mostly delta and gamma. So I do think that in the case of breast cancer, what we need to do is to work on more specific alpha inhibitors that will be safer,” he said.
During the oral abstracts session where Dr. Baselga presented the SANDPIPER results, Cynthia X Ma, MD, PhD, from Washington University School of Medicine in St. Louis, the invited discussant, agreed that the trial provides proof of concept that PI3K inhibition may be an effective therapeutic strategy in breast cancer.
“However, the modest progression-free survival improvement and significant toxicity profile does not support its clinical application,” she said.
SOURCE: : Baselga J et al. ASCO 2018 Abstract LBA1006 .
CHICAGO – Is two months of progression-free survival worth it if those months mean living with serious side effects?
For women with advanced estrogen receptor-positive, HER2-negative breast cancer, the combination of the PI3K inhibitor taselisib and the selective estrogen receptor modifier fulvestrant (Faslodex) bought two additional months of PFS, compared with fulvestrant alone, but at the cost of serious toxicities in half the patients treated with the combination, results of the SANDPIPER trial show.
“These results are positive, but I think we all agree they are modest,” lead investigator José Baselga, MD, PhD from Memorial Sloan Kettering Cancer Center in New York, said at a briefing at the annual meeting of the American Society of Clinical Oncology.
The “challenging tolerability” of the combination led to frequent treatment discontinuations, and may have limited the clinical benefit of the combination, he said, but added that the study serves as proof of principle that PI3K may be a bona fide target in advanced breast cancer.
ASCO expert Harold Burstein, MD, from the Dana-Farber Cancer Institute in Boston agreed that PI3K “is a very appealing target. It’s a mutation that probably is the most common in breast cancer when you do genomic sequencing, and it arises in other tumors as well.”
He likened the study findings, however, to a key opening a locked door, only to find that there is a chain latch on the other side preventing entry.
In an interview, Dr. Burstein said that despite the best efforts of Dr. Baselga and others to find a suitable approach to targeting the PI3K pathway, the evidence to date suggests that it may not be an important driver of breast cancer.
Taselisib is the first agent in its class to specifically block the PI3K alpha isoform that is found to be mutated in approximately 40% of advanced ER-positive breast cancer. The agent has been shown to offer clinical benefits in early trials for patients with head and neck and some gynecologic cancers.
In the phase 3 SANDPIPER trial, 516 women with locally advanced or metastatic ER-positive, HER2-negative breast cancer that had progressed or recurred following aromatase inhibitor therapy were enrolled and randomly assigned on a 2:1 basis to receive fulvestrant plus taselisib (340 patients) or fulvestrant plus a placebo (176 patients).
As noted, the median progression-free survival was 7.4 months for women who received the combination, compared with 5.4 months for controls. The stratified hazard ratio was 0.70 favoring taselisib (P = .0037).
But also as noted, the addition of taselisib “clearly led to toxicity,” Dr. Baselga said.
Serious adverse events occurred in 32% of patients in the fulvestrant/taselisib group, compared with 8.9% of controls. Grade 3 or greater side effects occurred in 49.5% vs. 16.4%, respectively, and side effects leading to discontinuation of taselisib occurred in 16.8% of patients, vs. 2.3% of those on placebo.
The primary toxicities were gastrointestinal effects, especially diarrhea, which occurred in 60.1% vs. 19.7% of patients (all grades). Hyperglycemia occurred in 40.4% of patients on taselisib, vs. 9.4% on placebo.
Dr. Baselga noted that the secondary endpoints of overall response rate, clinical benefit rate, and duration of response all favored taselisib.
Asked whether taselisib was the right agent in this setting, given the commercial availability of at least two other PI3K inhibitors – idelalisib (Zydelig) and copanlisib (Aliqopa) – Dr. Baselga agreed that another, more specific agent may offer similar or better efficacy with fewer off-target effects. He noted that taselisib is highly active against the alpha isoforms of PI3K, but also hits the delta and gamma isoforms.
“The side effects that we see that are limiting patients staying on [taselisib] are mostly delta and gamma. So I do think that in the case of breast cancer, what we need to do is to work on more specific alpha inhibitors that will be safer,” he said.
During the oral abstracts session where Dr. Baselga presented the SANDPIPER results, Cynthia X Ma, MD, PhD, from Washington University School of Medicine in St. Louis, the invited discussant, agreed that the trial provides proof of concept that PI3K inhibition may be an effective therapeutic strategy in breast cancer.
“However, the modest progression-free survival improvement and significant toxicity profile does not support its clinical application,” she said.
SOURCE: : Baselga J et al. ASCO 2018 Abstract LBA1006 .
REPORTING FROM ASCO 2018
Key clinical point:
Major finding: The combination of taselisib/fulvestrant extend median progression-free survival by two months.
Study details: Phase 3 randomized trial in 516 women with locally advanced or metastatic ER+/HER2- breast cancer.
Disclosures: The study was funded by F. Hoffman La-Roche. Dr. Baselga had disclosures related to GRAIL, Lilly, and Novartis, Infinity Pharmaceuticals, and Varian Medical Systems, PMV Pharma, and Juno Therapeutics. Dr. Burstein disclosed institutional research funding and speaker’s bureau activities for Novartis. Dr. Ma reported no relevant disclosures.
Source: Baselga et al. ASCO Abstract LBA1006.
Maintenance chemo boosts survival for youth with high-risk rhabdomyosarcoma
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.
The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated.
In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.
The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated.
In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Maintenance chemotherapy is life-prolonging for youth with high-risk rhabdomyosarcoma, finds a trial of 371 patients aged 0 to 21 years who had completed standard intensive therapy.
The 5-year rate of overall survival was 86.5% for those who received maintenance therapy with the combination of low-dose intravenous vinorelbine and oral cyclophosphamide, compared with 73.7% for those who did not, translating to a near halving of the risk of death (hazard ratio, 0.52; P = .0111). The regimen was well tolerated.
In an interview at the annual meeting of the American Society of Clinical Oncology, lead study author Gianni Bisogno, MD, PhD, discussed the risk-benefit profile of maintenance chemotherapy and the practice-changing nature of the new data. Dr. Bisogno, a professor at the University Hospital of Padova in Italy and chair of the European Paediatric Soft tissue Sarcoma Study Group, also described plans for a new trial that will explore alternate maintenance schedules and collaboration with colleagues in North America to further improve pediatric rhabdomyosarcoma outcomes.
REPORTING FROM ASCO 2018
AZD8871 delivered significant bronchodilation in two-week study
SAN DIEGO – , results from a phase 2a trial showed.
AZD8871 is a long-acting, bifunctional bronchodilator that combines a muscarinic antagonist and a beta-2 adrenoceptor agonist. “There are some interesting avenues that you can explore with such a molecule,” one of the study authors, Dave Singh, MD, said at an international conference of the American Thoracic Society. “First, theoretically, as a single molecule you will be able to deposit both the active ingredients to the same site in the lung. On a more practical note, if you want to add something else to a dual bronchodilator, which is essentially what AZD8871 is, this provides a platform. Perhaps that’s the most interesting use of this type of approach.”
Single doses of AZD8871 (400 mcg and 1,800 mcg) administered in COPD patients demonstrated sustained bronchodilation over 36 hours. In a study presented at the 2017 meeting of the European Respiratory Society, Dr. Singh and his associates found that AZD8871 1,800 mcg showed greater bronchodilation than both indacaterol and tiotropium for peak and trough FEV1.
For the current study, researchers at one site in the United Kingdom and one site in Germany conducted a phase 2 randomized, double-blind, placebo-controlled trial of AZD8871 in 42 patients aged 40-80 years with moderate to severe reversible COPD. Patients were randomized to receive repeated once-daily doses of AZD8871 100 mcg, 600 mcg, or placebo via a dry powder inhaler device for 14 days. Between-treatment washout periods were 28-35 days. “We keep the patients in-house on day one and day 14 of each treatment period, and we measure lung function over 24 hours,” said Dr. Singh, professor of clinical pharmacology and respiratory medicine at the University of Manchester, United Kingdom. “Patients were allowed to continue any pre-existing steroid therapy, but at the end of screening they had to withdraw any long-acting bronchodilator therapy.”
The primary efficacy endpoint was change from baseline trough FEV1 on day 15. Secondary endpoints included change from baseline in peak FEV1, total score of breathlessness, cough, sputum scale questionnaire, and rescue medication use.
At baseline, the mean age of the 42 patients was 64 years, and 67% were male. Their mean FEV1 was about 58% predicted, and their FEV1 absolute reversibility was a mean of 379 mL, “which is rather high,” he said.
Of the 42 randomized patients, 31 completed all three treatments. Both doses of AZD8871 had a positive, dose-dependent effect on FEV1, compared with placebo, and both doses demonstrated an onset of action within 15 minutes. On day 15, least square mean change from baseline differences in trough FEV1 for AZD8871 100 mcg and 600 mcg versus placebo were 161 mL and 260 mL, respectively.
A similar association was observed with peak FEV1, which between baseline and day 14 increased by 380 mL at the 100 mcg dose and by 420 mL at the 600 mcg dose, compared with placebo. Sustained bronchodilation was observed over 24 hours on both day 1 and day 14.
Statistically significant COPD symptom improvements, measured by breathlessness, cough and sputum scale (BCSS), were observed for AZD8871 600 mcg on day 8 (P=0.002) and day 14 (P less than 0.001), compared with placebo.
In addition, substantial symptomatic improvements were observed for AZD8871 600 mcg on D14 versus placebo (least square mean of -1.16). Similar results were observed for individual domains of the BCSS. “When you separate out the different components of the scale, most of this is driven by the change in breathlessness,” he said. “We were surprised that we could capture this in such a small number of patients.”
On days 1-8 and days 9-14, the researchers observed a statistically significant improvement in change from baseline rescue medication use for AZD8871 600 mcg (P less than 0.001) and 100 mcg (P=0.029 and P=0.012, respectively), compared with placebo.
The most common adverse events for patients in all three treatment groups were headache (21.4%) and worsening of COPD-related symptoms (14.3%). No dose-dependence was observed with any adverse event, including serious adverse events and/or those leading to discontinuation.
AstraZeneca, the developer of AZD8871, sponsored the study. Dr. Singh reported being a consultant to and receiving research support from AstraZeneca and numerous other pharmaceutical companies.
SOURCE: Singh, D., et al, Abstract 7708, ATS 2018.
SAN DIEGO – , results from a phase 2a trial showed.
AZD8871 is a long-acting, bifunctional bronchodilator that combines a muscarinic antagonist and a beta-2 adrenoceptor agonist. “There are some interesting avenues that you can explore with such a molecule,” one of the study authors, Dave Singh, MD, said at an international conference of the American Thoracic Society. “First, theoretically, as a single molecule you will be able to deposit both the active ingredients to the same site in the lung. On a more practical note, if you want to add something else to a dual bronchodilator, which is essentially what AZD8871 is, this provides a platform. Perhaps that’s the most interesting use of this type of approach.”
Single doses of AZD8871 (400 mcg and 1,800 mcg) administered in COPD patients demonstrated sustained bronchodilation over 36 hours. In a study presented at the 2017 meeting of the European Respiratory Society, Dr. Singh and his associates found that AZD8871 1,800 mcg showed greater bronchodilation than both indacaterol and tiotropium for peak and trough FEV1.
For the current study, researchers at one site in the United Kingdom and one site in Germany conducted a phase 2 randomized, double-blind, placebo-controlled trial of AZD8871 in 42 patients aged 40-80 years with moderate to severe reversible COPD. Patients were randomized to receive repeated once-daily doses of AZD8871 100 mcg, 600 mcg, or placebo via a dry powder inhaler device for 14 days. Between-treatment washout periods were 28-35 days. “We keep the patients in-house on day one and day 14 of each treatment period, and we measure lung function over 24 hours,” said Dr. Singh, professor of clinical pharmacology and respiratory medicine at the University of Manchester, United Kingdom. “Patients were allowed to continue any pre-existing steroid therapy, but at the end of screening they had to withdraw any long-acting bronchodilator therapy.”
The primary efficacy endpoint was change from baseline trough FEV1 on day 15. Secondary endpoints included change from baseline in peak FEV1, total score of breathlessness, cough, sputum scale questionnaire, and rescue medication use.
At baseline, the mean age of the 42 patients was 64 years, and 67% were male. Their mean FEV1 was about 58% predicted, and their FEV1 absolute reversibility was a mean of 379 mL, “which is rather high,” he said.
Of the 42 randomized patients, 31 completed all three treatments. Both doses of AZD8871 had a positive, dose-dependent effect on FEV1, compared with placebo, and both doses demonstrated an onset of action within 15 minutes. On day 15, least square mean change from baseline differences in trough FEV1 for AZD8871 100 mcg and 600 mcg versus placebo were 161 mL and 260 mL, respectively.
A similar association was observed with peak FEV1, which between baseline and day 14 increased by 380 mL at the 100 mcg dose and by 420 mL at the 600 mcg dose, compared with placebo. Sustained bronchodilation was observed over 24 hours on both day 1 and day 14.
Statistically significant COPD symptom improvements, measured by breathlessness, cough and sputum scale (BCSS), were observed for AZD8871 600 mcg on day 8 (P=0.002) and day 14 (P less than 0.001), compared with placebo.
In addition, substantial symptomatic improvements were observed for AZD8871 600 mcg on D14 versus placebo (least square mean of -1.16). Similar results were observed for individual domains of the BCSS. “When you separate out the different components of the scale, most of this is driven by the change in breathlessness,” he said. “We were surprised that we could capture this in such a small number of patients.”
On days 1-8 and days 9-14, the researchers observed a statistically significant improvement in change from baseline rescue medication use for AZD8871 600 mcg (P less than 0.001) and 100 mcg (P=0.029 and P=0.012, respectively), compared with placebo.
The most common adverse events for patients in all three treatment groups were headache (21.4%) and worsening of COPD-related symptoms (14.3%). No dose-dependence was observed with any adverse event, including serious adverse events and/or those leading to discontinuation.
AstraZeneca, the developer of AZD8871, sponsored the study. Dr. Singh reported being a consultant to and receiving research support from AstraZeneca and numerous other pharmaceutical companies.
SOURCE: Singh, D., et al, Abstract 7708, ATS 2018.
SAN DIEGO – , results from a phase 2a trial showed.
AZD8871 is a long-acting, bifunctional bronchodilator that combines a muscarinic antagonist and a beta-2 adrenoceptor agonist. “There are some interesting avenues that you can explore with such a molecule,” one of the study authors, Dave Singh, MD, said at an international conference of the American Thoracic Society. “First, theoretically, as a single molecule you will be able to deposit both the active ingredients to the same site in the lung. On a more practical note, if you want to add something else to a dual bronchodilator, which is essentially what AZD8871 is, this provides a platform. Perhaps that’s the most interesting use of this type of approach.”
Single doses of AZD8871 (400 mcg and 1,800 mcg) administered in COPD patients demonstrated sustained bronchodilation over 36 hours. In a study presented at the 2017 meeting of the European Respiratory Society, Dr. Singh and his associates found that AZD8871 1,800 mcg showed greater bronchodilation than both indacaterol and tiotropium for peak and trough FEV1.
For the current study, researchers at one site in the United Kingdom and one site in Germany conducted a phase 2 randomized, double-blind, placebo-controlled trial of AZD8871 in 42 patients aged 40-80 years with moderate to severe reversible COPD. Patients were randomized to receive repeated once-daily doses of AZD8871 100 mcg, 600 mcg, or placebo via a dry powder inhaler device for 14 days. Between-treatment washout periods were 28-35 days. “We keep the patients in-house on day one and day 14 of each treatment period, and we measure lung function over 24 hours,” said Dr. Singh, professor of clinical pharmacology and respiratory medicine at the University of Manchester, United Kingdom. “Patients were allowed to continue any pre-existing steroid therapy, but at the end of screening they had to withdraw any long-acting bronchodilator therapy.”
The primary efficacy endpoint was change from baseline trough FEV1 on day 15. Secondary endpoints included change from baseline in peak FEV1, total score of breathlessness, cough, sputum scale questionnaire, and rescue medication use.
At baseline, the mean age of the 42 patients was 64 years, and 67% were male. Their mean FEV1 was about 58% predicted, and their FEV1 absolute reversibility was a mean of 379 mL, “which is rather high,” he said.
Of the 42 randomized patients, 31 completed all three treatments. Both doses of AZD8871 had a positive, dose-dependent effect on FEV1, compared with placebo, and both doses demonstrated an onset of action within 15 minutes. On day 15, least square mean change from baseline differences in trough FEV1 for AZD8871 100 mcg and 600 mcg versus placebo were 161 mL and 260 mL, respectively.
A similar association was observed with peak FEV1, which between baseline and day 14 increased by 380 mL at the 100 mcg dose and by 420 mL at the 600 mcg dose, compared with placebo. Sustained bronchodilation was observed over 24 hours on both day 1 and day 14.
Statistically significant COPD symptom improvements, measured by breathlessness, cough and sputum scale (BCSS), were observed for AZD8871 600 mcg on day 8 (P=0.002) and day 14 (P less than 0.001), compared with placebo.
In addition, substantial symptomatic improvements were observed for AZD8871 600 mcg on D14 versus placebo (least square mean of -1.16). Similar results were observed for individual domains of the BCSS. “When you separate out the different components of the scale, most of this is driven by the change in breathlessness,” he said. “We were surprised that we could capture this in such a small number of patients.”
On days 1-8 and days 9-14, the researchers observed a statistically significant improvement in change from baseline rescue medication use for AZD8871 600 mcg (P less than 0.001) and 100 mcg (P=0.029 and P=0.012, respectively), compared with placebo.
The most common adverse events for patients in all three treatment groups were headache (21.4%) and worsening of COPD-related symptoms (14.3%). No dose-dependence was observed with any adverse event, including serious adverse events and/or those leading to discontinuation.
AstraZeneca, the developer of AZD8871, sponsored the study. Dr. Singh reported being a consultant to and receiving research support from AstraZeneca and numerous other pharmaceutical companies.
SOURCE: Singh, D., et al, Abstract 7708, ATS 2018.
REPORTING FROM ATS 2018
Key clinical point: Once daily doses of AZD8871 100 mcg and 600 mcg elicited significant and clinically relevant differences in trough FEV1, compared with placebo.
Major finding: On day 15, least square mean change from baseline differences in trough FEV1 for AZD8871 100 mcg and 600 mcg versus placebo were 161 mL and 260 mL, respectively.
Study details: A phase 2a trial of 42 patients aged 40-80 years with moderate to severe reversible COPD.
Disclosures: AstraZeneca sponsored the study. Dr. Singh reported financial affiliations with AstraZeneca and numerous other pharmaceutical companies.Source: Singh, D., et al. Abstract 7708, ATS 2018.
TAILORx: Most women with intermediate risk ER+ breast cancer can safely skip chemo
CHICAGO – New data from the TAILORx trial are welcome news for women with HR-positive, HER2-negative, axillary node–negative early-stage breast cancer and their oncologists caught in the gray area surrounding the need for adjuvant chemotherapy.
Results of the noninferiority phase 3 trial—the largest adjuvant breast cancer treatment trial ever conducted—show that among the 6,711 women with an intermediate Oncotype DX Breast Recurrence Score (11-25), those who received only endocrine therapy and skipped adjuvant chemotherapy did not have worse invasive disease-free survival than counterparts who received both (hazard ratio, 1.08; P=.26).
The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy alone and 84.3% with both chemotherapy and endocrine therapy, and the pattern was essentially the same for freedom from any recurrence and distant recurrence, and overall survival.
The findings are practice changing, according to lead study author Joseph A. Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and vice-chair of the ECOG-ACRIN Cancer Research Group.
In a video interview at the annual meeting of the American Society of Clinical Oncology, he discussed implications of the new data for decision making, results of interaction analyses showing that one size does not fit all and certain women with intermediate recurrence scores do derive benefit from adjuvant chemotherapy, as well as plans to use the tumor samples for future analyses on those that do recur.
CHICAGO – New data from the TAILORx trial are welcome news for women with HR-positive, HER2-negative, axillary node–negative early-stage breast cancer and their oncologists caught in the gray area surrounding the need for adjuvant chemotherapy.
Results of the noninferiority phase 3 trial—the largest adjuvant breast cancer treatment trial ever conducted—show that among the 6,711 women with an intermediate Oncotype DX Breast Recurrence Score (11-25), those who received only endocrine therapy and skipped adjuvant chemotherapy did not have worse invasive disease-free survival than counterparts who received both (hazard ratio, 1.08; P=.26).
The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy alone and 84.3% with both chemotherapy and endocrine therapy, and the pattern was essentially the same for freedom from any recurrence and distant recurrence, and overall survival.
The findings are practice changing, according to lead study author Joseph A. Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and vice-chair of the ECOG-ACRIN Cancer Research Group.
In a video interview at the annual meeting of the American Society of Clinical Oncology, he discussed implications of the new data for decision making, results of interaction analyses showing that one size does not fit all and certain women with intermediate recurrence scores do derive benefit from adjuvant chemotherapy, as well as plans to use the tumor samples for future analyses on those that do recur.
CHICAGO – New data from the TAILORx trial are welcome news for women with HR-positive, HER2-negative, axillary node–negative early-stage breast cancer and their oncologists caught in the gray area surrounding the need for adjuvant chemotherapy.
Results of the noninferiority phase 3 trial—the largest adjuvant breast cancer treatment trial ever conducted—show that among the 6,711 women with an intermediate Oncotype DX Breast Recurrence Score (11-25), those who received only endocrine therapy and skipped adjuvant chemotherapy did not have worse invasive disease-free survival than counterparts who received both (hazard ratio, 1.08; P=.26).
The 9-year rate of invasive disease–free survival was 83.3% with endocrine therapy alone and 84.3% with both chemotherapy and endocrine therapy, and the pattern was essentially the same for freedom from any recurrence and distant recurrence, and overall survival.
The findings are practice changing, according to lead study author Joseph A. Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and vice-chair of the ECOG-ACRIN Cancer Research Group.
In a video interview at the annual meeting of the American Society of Clinical Oncology, he discussed implications of the new data for decision making, results of interaction analyses showing that one size does not fit all and certain women with intermediate recurrence scores do derive benefit from adjuvant chemotherapy, as well as plans to use the tumor samples for future analyses on those that do recur.
REPORTING FROM ASCO 2018
Barrett’s segment length, low-grade dysplasia tied to increased risk of neoplastic progression
WASHINGTON – , investigators here reported, but risk of esophageal progression from Barrett’s esophagus to adenocarcinoma remains low.
Tracking neoplastic progression is of prime importance in patients with Barrett’s esophagus (BE) because it can lead to the formation of esophageal adenocarcinoma (EAD), Esther Klaver of the Academic Medical Center of the University of Amsterdam noted at the annual Digestive Disease Week. By the time many patients present with symptoms, they are at an incurable stage of the disease and have 5-year survival rates below 20%. Endoscopic surveillance of patients with BE can detect neoplastic progression and EAD when it is still curable.
Ms. Klaver and her colleagues attempted to conduct the “perfect study” by observing patients with BE to identify endoscopic and clinical factors associated with increased risk of neoplastic progression. They did this by establishing a surveillance program to track disease progression that enrolled 987 patients from 2003 to 2017 at six community-based hospitals. The patients who enrolled had been diagnosed with BE and identified via a Dutch pathology registry or were newly diagnosed BE patients. Those with any history of EAD or high-grade dysplasia (HGD) were not included.
Ms. Klaver and her colleagues found that after a 7-year follow-up period the annual risk of progression to HGD or EAD was 0.79% per patient year, with 68 of the 987 patients progressing. Of the patients who progressed, 27 progressed to HGD (40%), and 41 progressed to EAD (60%). An overwhelming majority of patients received endoscopic management (59 patients, 87%), while some patients required surgery (9, 13%). Only 32 (3%) patients in the entire study population were lost to follow-up.
Low-grade dysplasia at baseline was the factor with the highest risk for esophageal progression, with a hazard ratio (HR) of 2.33 (95% CI, 1.27-4.29). Longer BE length (HR 1.07, 95% CI 1.04-1.10) and age at baseline (HR 1.17, 95% CI 1.12-1.24) were less associated with risk of HGD or EAD, but still significant.
Ms. Klaver pointed out that this study is unique in its design. The long-term follow-up and the focus on strict adherence to guidelines and optimal surveillance set this study apart from many BE studies.
“We tried to perform the perfect, optimal, prospective Barrett’s surveillance study in a large cohort with almost 1,000 patients with a median follow-up of almost 8 years.” Ms. Klaver said. “We have done this in a community, nonacademic setting, with the average Barrett’s patient. We have showed you that even with perfect surveillance that progression risk is low, with only 68 of almost 1,000 patients showing progression.”
The study was managed by tertiary referral centers that had two research nurses who attended surveillance endoscopies to ensure that guidelines were followed. Additionally, all endoscopies were performed by a dedicated endoscopist. As part of the endoscopy visit, patients filled out questionnaires containing demographic and clinical data. Researchers also retrospectively collected any prior surveillance data for patients who had previously been under histologic and endoscopic surveillance.
Ms. Klaver and her colleagues had no financial conflicts of interest to report.
SOURCE: Klaver E. et al. Gastroenterology. 154 (6). Abstract 10. doi: 10.1016/S0016-5085(18)30500-6.
WASHINGTON – , investigators here reported, but risk of esophageal progression from Barrett’s esophagus to adenocarcinoma remains low.
Tracking neoplastic progression is of prime importance in patients with Barrett’s esophagus (BE) because it can lead to the formation of esophageal adenocarcinoma (EAD), Esther Klaver of the Academic Medical Center of the University of Amsterdam noted at the annual Digestive Disease Week. By the time many patients present with symptoms, they are at an incurable stage of the disease and have 5-year survival rates below 20%. Endoscopic surveillance of patients with BE can detect neoplastic progression and EAD when it is still curable.
Ms. Klaver and her colleagues attempted to conduct the “perfect study” by observing patients with BE to identify endoscopic and clinical factors associated with increased risk of neoplastic progression. They did this by establishing a surveillance program to track disease progression that enrolled 987 patients from 2003 to 2017 at six community-based hospitals. The patients who enrolled had been diagnosed with BE and identified via a Dutch pathology registry or were newly diagnosed BE patients. Those with any history of EAD or high-grade dysplasia (HGD) were not included.
Ms. Klaver and her colleagues found that after a 7-year follow-up period the annual risk of progression to HGD or EAD was 0.79% per patient year, with 68 of the 987 patients progressing. Of the patients who progressed, 27 progressed to HGD (40%), and 41 progressed to EAD (60%). An overwhelming majority of patients received endoscopic management (59 patients, 87%), while some patients required surgery (9, 13%). Only 32 (3%) patients in the entire study population were lost to follow-up.
Low-grade dysplasia at baseline was the factor with the highest risk for esophageal progression, with a hazard ratio (HR) of 2.33 (95% CI, 1.27-4.29). Longer BE length (HR 1.07, 95% CI 1.04-1.10) and age at baseline (HR 1.17, 95% CI 1.12-1.24) were less associated with risk of HGD or EAD, but still significant.
Ms. Klaver pointed out that this study is unique in its design. The long-term follow-up and the focus on strict adherence to guidelines and optimal surveillance set this study apart from many BE studies.
“We tried to perform the perfect, optimal, prospective Barrett’s surveillance study in a large cohort with almost 1,000 patients with a median follow-up of almost 8 years.” Ms. Klaver said. “We have done this in a community, nonacademic setting, with the average Barrett’s patient. We have showed you that even with perfect surveillance that progression risk is low, with only 68 of almost 1,000 patients showing progression.”
The study was managed by tertiary referral centers that had two research nurses who attended surveillance endoscopies to ensure that guidelines were followed. Additionally, all endoscopies were performed by a dedicated endoscopist. As part of the endoscopy visit, patients filled out questionnaires containing demographic and clinical data. Researchers also retrospectively collected any prior surveillance data for patients who had previously been under histologic and endoscopic surveillance.
Ms. Klaver and her colleagues had no financial conflicts of interest to report.
SOURCE: Klaver E. et al. Gastroenterology. 154 (6). Abstract 10. doi: 10.1016/S0016-5085(18)30500-6.
WASHINGTON – , investigators here reported, but risk of esophageal progression from Barrett’s esophagus to adenocarcinoma remains low.
Tracking neoplastic progression is of prime importance in patients with Barrett’s esophagus (BE) because it can lead to the formation of esophageal adenocarcinoma (EAD), Esther Klaver of the Academic Medical Center of the University of Amsterdam noted at the annual Digestive Disease Week. By the time many patients present with symptoms, they are at an incurable stage of the disease and have 5-year survival rates below 20%. Endoscopic surveillance of patients with BE can detect neoplastic progression and EAD when it is still curable.
Ms. Klaver and her colleagues attempted to conduct the “perfect study” by observing patients with BE to identify endoscopic and clinical factors associated with increased risk of neoplastic progression. They did this by establishing a surveillance program to track disease progression that enrolled 987 patients from 2003 to 2017 at six community-based hospitals. The patients who enrolled had been diagnosed with BE and identified via a Dutch pathology registry or were newly diagnosed BE patients. Those with any history of EAD or high-grade dysplasia (HGD) were not included.
Ms. Klaver and her colleagues found that after a 7-year follow-up period the annual risk of progression to HGD or EAD was 0.79% per patient year, with 68 of the 987 patients progressing. Of the patients who progressed, 27 progressed to HGD (40%), and 41 progressed to EAD (60%). An overwhelming majority of patients received endoscopic management (59 patients, 87%), while some patients required surgery (9, 13%). Only 32 (3%) patients in the entire study population were lost to follow-up.
Low-grade dysplasia at baseline was the factor with the highest risk for esophageal progression, with a hazard ratio (HR) of 2.33 (95% CI, 1.27-4.29). Longer BE length (HR 1.07, 95% CI 1.04-1.10) and age at baseline (HR 1.17, 95% CI 1.12-1.24) were less associated with risk of HGD or EAD, but still significant.
Ms. Klaver pointed out that this study is unique in its design. The long-term follow-up and the focus on strict adherence to guidelines and optimal surveillance set this study apart from many BE studies.
“We tried to perform the perfect, optimal, prospective Barrett’s surveillance study in a large cohort with almost 1,000 patients with a median follow-up of almost 8 years.” Ms. Klaver said. “We have done this in a community, nonacademic setting, with the average Barrett’s patient. We have showed you that even with perfect surveillance that progression risk is low, with only 68 of almost 1,000 patients showing progression.”
The study was managed by tertiary referral centers that had two research nurses who attended surveillance endoscopies to ensure that guidelines were followed. Additionally, all endoscopies were performed by a dedicated endoscopist. As part of the endoscopy visit, patients filled out questionnaires containing demographic and clinical data. Researchers also retrospectively collected any prior surveillance data for patients who had previously been under histologic and endoscopic surveillance.
Ms. Klaver and her colleagues had no financial conflicts of interest to report.
SOURCE: Klaver E. et al. Gastroenterology. 154 (6). Abstract 10. doi: 10.1016/S0016-5085(18)30500-6.
REPORTING FROM DDW 2018
Key clinical point: Barrett’s segment length and low-grade dysplasia are associated with neoplastic progression.
Major finding: Low-grade dysplasia at baseline is associated with an increased risk of high-grade dysplasia or esophageal adenocarcinoma, hazard ratio of 2.38 (1.30 - 4.36).
Study details: This study was a prospective, multi-center cohort study involving 986 patients receiving treatment in six Dutch community-based hospitals from 2003 to 2017.
Disclosures: The study author did not report any financial disclosures.
Source: Klaver E et al. Gastroenterology. 154 (6). Abstract 10. doi: 10.1016/S0016-5085(18)30500-6.
COPD patient subset gains no benefit from low-dose theophylline
, results from a large trial funded by the United Kingdom found.
“Globally, theophylline was used for decades as a bronchodilator,” one of the study authors, David B. Price, MB BChir, said at an international conference of the American Thoracic Society. “The problem is theophylline has a narrow therapeutic index, it requires some blood monitoring, and it has been replaced by more effective inhaled bronchodilators. However, there has been a lot of discussion about whether low-dose theophylline has anti-inflammatory effects on its own and whether it increases sensitivity to inhaled steroids in COPD.”
According to the 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, there is “limited and contradictory evidence regarding the effect of low-dose theophylline on exacerbation rates,” and its clinical relevance has “not yet been fully established.” Dr. Price, a professor of primary care respiratory medicine at the University of Aberdeen, United Kingdom, and his associates hypothesized that the addition of low-dose theophylline to inhaled steroid therapy in COPD would reduce the risk of moderate to severe COPD exacerbations after one year of treatment. “If it worked, it would be wonderful; it would save the National Health Service a fortune,” he said.
In a government-funded trial known as Theophylline With Inhaled Corticosteroids (TWICS), people aged 40 years and older with COPD on a drug regimen including inhaled corticosteroids with a history of at least two exacerbations treated with antibiotics and/or oral corticosteroids in the previous year were recruited in 121 U.K. primary and secondary care sites from January 2014 through August 2016. They were randomized to receive low-dose theophylline or placebo for one year. Theophylline dose (200 mg once/twice a day) was determined by ideal body weight and smoking status. Primary outcome was the number of participant-reported exacerbations in the one year treatment period treated with antibiotics and/or oral corticosteroids. Participants were assessed six and 12 months after randomization. The study was powered to detect a 15% reduction in exacerbations and aimed to recruit 1,424 participants.
In all, 1,578 people were randomized: 791 to theophylline and 787 to placebo. Of these, primary outcome data were available for 98% of participants: 772 in the theophylline group and 764 in the placebo group, which amounted to 1,489 person-years of follow-up data. The mean age of patients was 68 years, 54% were male, 32% currently smoked, 80% were using inhaled corticosteroids/long-acting beta 2-agonists/long-acting muscarinic agents, and their mean FEV1 was 51.7% predicted.
Slightly more than one-quarter of study participants (26%) ceased study medication. Dr. Price said that this was balanced between the theophylline and placebo groups and mitigated by over-recruitment and a high rate of follow-up.
He reported that there were 3,430 moderate to severe exacerbations: 1,727 in the theophylline group and 1,703 in the placebo group. The mean number of exacerbations in participants allocated to theophylline and placebo groups were essentially the same: 2.24 vs. 2.23. However, there were a fewer number of exacerbations that required hospitalization in the theophylline group, compared with the placebo groups (0.17 vs. 0.24, for an adjusted rate ratio of 0.72). Dr. Price was quick to point out that this finding applied to a relatively small number of study participants, about 3% overall.
“How you interpret this, I don’t know,” he said. “Our conclusion is that in the broad population there is no benefit [of low-dose theophylline], but maybe someone might want to study its use in frequent exacerbation patients who are getting hospitalized.”
The study was funded by the National Institute for Health Research (NIHR), United Kingdom. Dr. Price reported having no financial disclosures.
SOURCE: Price, D., et al, Abstract 7709, ATS 2018.
, results from a large trial funded by the United Kingdom found.
“Globally, theophylline was used for decades as a bronchodilator,” one of the study authors, David B. Price, MB BChir, said at an international conference of the American Thoracic Society. “The problem is theophylline has a narrow therapeutic index, it requires some blood monitoring, and it has been replaced by more effective inhaled bronchodilators. However, there has been a lot of discussion about whether low-dose theophylline has anti-inflammatory effects on its own and whether it increases sensitivity to inhaled steroids in COPD.”
According to the 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, there is “limited and contradictory evidence regarding the effect of low-dose theophylline on exacerbation rates,” and its clinical relevance has “not yet been fully established.” Dr. Price, a professor of primary care respiratory medicine at the University of Aberdeen, United Kingdom, and his associates hypothesized that the addition of low-dose theophylline to inhaled steroid therapy in COPD would reduce the risk of moderate to severe COPD exacerbations after one year of treatment. “If it worked, it would be wonderful; it would save the National Health Service a fortune,” he said.
In a government-funded trial known as Theophylline With Inhaled Corticosteroids (TWICS), people aged 40 years and older with COPD on a drug regimen including inhaled corticosteroids with a history of at least two exacerbations treated with antibiotics and/or oral corticosteroids in the previous year were recruited in 121 U.K. primary and secondary care sites from January 2014 through August 2016. They were randomized to receive low-dose theophylline or placebo for one year. Theophylline dose (200 mg once/twice a day) was determined by ideal body weight and smoking status. Primary outcome was the number of participant-reported exacerbations in the one year treatment period treated with antibiotics and/or oral corticosteroids. Participants were assessed six and 12 months after randomization. The study was powered to detect a 15% reduction in exacerbations and aimed to recruit 1,424 participants.
In all, 1,578 people were randomized: 791 to theophylline and 787 to placebo. Of these, primary outcome data were available for 98% of participants: 772 in the theophylline group and 764 in the placebo group, which amounted to 1,489 person-years of follow-up data. The mean age of patients was 68 years, 54% were male, 32% currently smoked, 80% were using inhaled corticosteroids/long-acting beta 2-agonists/long-acting muscarinic agents, and their mean FEV1 was 51.7% predicted.
Slightly more than one-quarter of study participants (26%) ceased study medication. Dr. Price said that this was balanced between the theophylline and placebo groups and mitigated by over-recruitment and a high rate of follow-up.
He reported that there were 3,430 moderate to severe exacerbations: 1,727 in the theophylline group and 1,703 in the placebo group. The mean number of exacerbations in participants allocated to theophylline and placebo groups were essentially the same: 2.24 vs. 2.23. However, there were a fewer number of exacerbations that required hospitalization in the theophylline group, compared with the placebo groups (0.17 vs. 0.24, for an adjusted rate ratio of 0.72). Dr. Price was quick to point out that this finding applied to a relatively small number of study participants, about 3% overall.
“How you interpret this, I don’t know,” he said. “Our conclusion is that in the broad population there is no benefit [of low-dose theophylline], but maybe someone might want to study its use in frequent exacerbation patients who are getting hospitalized.”
The study was funded by the National Institute for Health Research (NIHR), United Kingdom. Dr. Price reported having no financial disclosures.
SOURCE: Price, D., et al, Abstract 7709, ATS 2018.
, results from a large trial funded by the United Kingdom found.
“Globally, theophylline was used for decades as a bronchodilator,” one of the study authors, David B. Price, MB BChir, said at an international conference of the American Thoracic Society. “The problem is theophylline has a narrow therapeutic index, it requires some blood monitoring, and it has been replaced by more effective inhaled bronchodilators. However, there has been a lot of discussion about whether low-dose theophylline has anti-inflammatory effects on its own and whether it increases sensitivity to inhaled steroids in COPD.”
According to the 2018 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, there is “limited and contradictory evidence regarding the effect of low-dose theophylline on exacerbation rates,” and its clinical relevance has “not yet been fully established.” Dr. Price, a professor of primary care respiratory medicine at the University of Aberdeen, United Kingdom, and his associates hypothesized that the addition of low-dose theophylline to inhaled steroid therapy in COPD would reduce the risk of moderate to severe COPD exacerbations after one year of treatment. “If it worked, it would be wonderful; it would save the National Health Service a fortune,” he said.
In a government-funded trial known as Theophylline With Inhaled Corticosteroids (TWICS), people aged 40 years and older with COPD on a drug regimen including inhaled corticosteroids with a history of at least two exacerbations treated with antibiotics and/or oral corticosteroids in the previous year were recruited in 121 U.K. primary and secondary care sites from January 2014 through August 2016. They were randomized to receive low-dose theophylline or placebo for one year. Theophylline dose (200 mg once/twice a day) was determined by ideal body weight and smoking status. Primary outcome was the number of participant-reported exacerbations in the one year treatment period treated with antibiotics and/or oral corticosteroids. Participants were assessed six and 12 months after randomization. The study was powered to detect a 15% reduction in exacerbations and aimed to recruit 1,424 participants.
In all, 1,578 people were randomized: 791 to theophylline and 787 to placebo. Of these, primary outcome data were available for 98% of participants: 772 in the theophylline group and 764 in the placebo group, which amounted to 1,489 person-years of follow-up data. The mean age of patients was 68 years, 54% were male, 32% currently smoked, 80% were using inhaled corticosteroids/long-acting beta 2-agonists/long-acting muscarinic agents, and their mean FEV1 was 51.7% predicted.
Slightly more than one-quarter of study participants (26%) ceased study medication. Dr. Price said that this was balanced between the theophylline and placebo groups and mitigated by over-recruitment and a high rate of follow-up.
He reported that there were 3,430 moderate to severe exacerbations: 1,727 in the theophylline group and 1,703 in the placebo group. The mean number of exacerbations in participants allocated to theophylline and placebo groups were essentially the same: 2.24 vs. 2.23. However, there were a fewer number of exacerbations that required hospitalization in the theophylline group, compared with the placebo groups (0.17 vs. 0.24, for an adjusted rate ratio of 0.72). Dr. Price was quick to point out that this finding applied to a relatively small number of study participants, about 3% overall.
“How you interpret this, I don’t know,” he said. “Our conclusion is that in the broad population there is no benefit [of low-dose theophylline], but maybe someone might want to study its use in frequent exacerbation patients who are getting hospitalized.”
The study was funded by the National Institute for Health Research (NIHR), United Kingdom. Dr. Price reported having no financial disclosures.
SOURCE: Price, D., et al, Abstract 7709, ATS 2018.
AT ATS 2018
Key clinical point: Among COPD patients at high risk of exacerbation, adding low-dose oral theophylline to a drug regimen that includes an inhaled corticosteroid provides no overall clinical benefit.
Major finding: The number of exacerbations was 2.24 in participants allocated to theophylline and 2.23 for participants allocated to placebo.
Study details: A trial of 1,578 people with COPD and a history of at least two exacerbations in the previous year who were randomized to receive low-dose theophylline or placebo for one year.
Disclosures: The study was funded by National Institute for Health Research (NIHR), United Kingdom. Dr. Price reported having no financial disclosures.
Source: Price, D., et al. Abstract 7709, ATS 2018.
Atezolizumab has PFS benefit in first-line squamous NSCLC
CHICAGO – Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to first-line chemotherapy for squamous non–small cell lung cancer (NSCLC) improves outcomes, according to results of the IMpower131 trial reported at the annual meeting of the American Society of Clinical Oncology.
“Squamous NSCLC remains a very difficult to treat disease, and there have been very limited new treatment options presented to us over the last few decades,” lead study author Robert M. Jotte, MD, PhD, medical director and co-chair, USON Thoracic Committee, Rocky Mountain Cancer Centers in Denver, said in a press briefing. Chemotherapy is still considered standard of care in the first-line setting.
Main results showed that compared with chemotherapy (carboplatin and nab-paclitaxel) alone, the combination of atezolizumab and chemotherapy reduced the risk of progression-free survival events by 29%, prolonging median time to an event by about a month. Findings were similar regardless of the level of PD-L1 positivity, although reduction in events was greatest for patients whose tumors were highly positive.
Median overall survival was about 14 months in each arm, with no significant difference, although results are not yet mature.
“IMpower131 data show that patients with advanced squamous NSCLC benefit more from initial treatment with atezolizumab plus chemotherapy than from chemotherapy alone,” Dr. Jotte summarized. The combination “has a manageable safety profile consistent with known safety risks of the individual therapies, with no new safety signals identified.”
The investigators are continuing to follow overall survival, with the next interim analysis expected to occur later this year. “In the IMpower131 study, patients were not allowed to cross over. However, among patients who were monitored and followed for subsequent therapy, nearly half went on to receive immuno-oncologic therapies beyond the study, so that will likely taint the overall survival curves,” he noted.
Patients receiving chemotherapy for advanced lung cancer are devastated when told that their disease has progressed, he commented. “What we see with the results of this study is that we can actually double the chance that they don’t have to hear that bad news in the first year of treatment.”
“We hope that the results seen with progression-free survival translate to improved overall survival. If and when that is shown, I think we will clearly have a new standard of care for the front-line treatment of squamous cell NSCLC,” concluded Dr. Graham, who is also medical director at the Levine Cancer Institute in Charlotte, N.C.
Study details
With a median follow-up of 17.1 months in IMpower131, median progression-free survival was 5.6 months with chemotherapy alone and 6.3 months when atezolizumab was added to chemotherapy (hazard ratio, 0.71; P = .0001).
There was a doubling of the 12-month progression-free survival rate, from 12.0% to 24.7%, Dr. Jotte reported.
Atezolizumab improved progression-free survival across levels of PD-L1 expression, but benefit was most pronounced in patients with tumors having a high level of this biomarker (hazard ratio, 0.44).
Findings were similar for response, with a higher overall response rate seen with atezolizumab plus chemotherapy versus chemotherapy alone (49% vs. 41%) and greatest difference in the subgroup whose tumors were highly PD-L1 positive (60% vs. 33%). Median duration of response was 7.2 months with the immunotherapy and 5.2 months without it.
Interim overall survival results showed that patients lived a median of 14.0 months with atezolizumab plus chemotherapy and 13.9 months with chemotherapy alone (hazard ratio, 0.96; P = .6931).
Data from a third arm of the IMpower131 trial, in which atezolizumab was added to carboplatin plus paclitaxel, have not reached a point where statistical analyses can be done, according to Dr. Jotte.
A related phase 3 trial, IMpower150, is testing addition of atezolizumab to chemotherapy, with or without bevacizumab, as first-line therapy for metastatic nonsquamous NSCLC. Investigators will be reporting results at the meeting for both overall survival (abstract 9002) and patient-reported outcomes (abstract 9047).
Dr. Jotte disclosed that he is on the speakers’ bureau for Bristol-Myers Squibb, and that he receives travel, accommodations, and/or expenses, as well as honoraria from Bristol-Myers Squibb. The study received funding from F. Hoffmann-La Roche Ltd.
SOURCE: Jotte et al. ASCO 2018 Abstract LBA9000.
CHICAGO – Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to first-line chemotherapy for squamous non–small cell lung cancer (NSCLC) improves outcomes, according to results of the IMpower131 trial reported at the annual meeting of the American Society of Clinical Oncology.
“Squamous NSCLC remains a very difficult to treat disease, and there have been very limited new treatment options presented to us over the last few decades,” lead study author Robert M. Jotte, MD, PhD, medical director and co-chair, USON Thoracic Committee, Rocky Mountain Cancer Centers in Denver, said in a press briefing. Chemotherapy is still considered standard of care in the first-line setting.
Main results showed that compared with chemotherapy (carboplatin and nab-paclitaxel) alone, the combination of atezolizumab and chemotherapy reduced the risk of progression-free survival events by 29%, prolonging median time to an event by about a month. Findings were similar regardless of the level of PD-L1 positivity, although reduction in events was greatest for patients whose tumors were highly positive.
Median overall survival was about 14 months in each arm, with no significant difference, although results are not yet mature.
“IMpower131 data show that patients with advanced squamous NSCLC benefit more from initial treatment with atezolizumab plus chemotherapy than from chemotherapy alone,” Dr. Jotte summarized. The combination “has a manageable safety profile consistent with known safety risks of the individual therapies, with no new safety signals identified.”
The investigators are continuing to follow overall survival, with the next interim analysis expected to occur later this year. “In the IMpower131 study, patients were not allowed to cross over. However, among patients who were monitored and followed for subsequent therapy, nearly half went on to receive immuno-oncologic therapies beyond the study, so that will likely taint the overall survival curves,” he noted.
Patients receiving chemotherapy for advanced lung cancer are devastated when told that their disease has progressed, he commented. “What we see with the results of this study is that we can actually double the chance that they don’t have to hear that bad news in the first year of treatment.”
“We hope that the results seen with progression-free survival translate to improved overall survival. If and when that is shown, I think we will clearly have a new standard of care for the front-line treatment of squamous cell NSCLC,” concluded Dr. Graham, who is also medical director at the Levine Cancer Institute in Charlotte, N.C.
Study details
With a median follow-up of 17.1 months in IMpower131, median progression-free survival was 5.6 months with chemotherapy alone and 6.3 months when atezolizumab was added to chemotherapy (hazard ratio, 0.71; P = .0001).
There was a doubling of the 12-month progression-free survival rate, from 12.0% to 24.7%, Dr. Jotte reported.
Atezolizumab improved progression-free survival across levels of PD-L1 expression, but benefit was most pronounced in patients with tumors having a high level of this biomarker (hazard ratio, 0.44).
Findings were similar for response, with a higher overall response rate seen with atezolizumab plus chemotherapy versus chemotherapy alone (49% vs. 41%) and greatest difference in the subgroup whose tumors were highly PD-L1 positive (60% vs. 33%). Median duration of response was 7.2 months with the immunotherapy and 5.2 months without it.
Interim overall survival results showed that patients lived a median of 14.0 months with atezolizumab plus chemotherapy and 13.9 months with chemotherapy alone (hazard ratio, 0.96; P = .6931).
Data from a third arm of the IMpower131 trial, in which atezolizumab was added to carboplatin plus paclitaxel, have not reached a point where statistical analyses can be done, according to Dr. Jotte.
A related phase 3 trial, IMpower150, is testing addition of atezolizumab to chemotherapy, with or without bevacizumab, as first-line therapy for metastatic nonsquamous NSCLC. Investigators will be reporting results at the meeting for both overall survival (abstract 9002) and patient-reported outcomes (abstract 9047).
Dr. Jotte disclosed that he is on the speakers’ bureau for Bristol-Myers Squibb, and that he receives travel, accommodations, and/or expenses, as well as honoraria from Bristol-Myers Squibb. The study received funding from F. Hoffmann-La Roche Ltd.
SOURCE: Jotte et al. ASCO 2018 Abstract LBA9000.
CHICAGO – Adding the immune checkpoint inhibitor atezolizumab (Tecentriq) to first-line chemotherapy for squamous non–small cell lung cancer (NSCLC) improves outcomes, according to results of the IMpower131 trial reported at the annual meeting of the American Society of Clinical Oncology.
“Squamous NSCLC remains a very difficult to treat disease, and there have been very limited new treatment options presented to us over the last few decades,” lead study author Robert M. Jotte, MD, PhD, medical director and co-chair, USON Thoracic Committee, Rocky Mountain Cancer Centers in Denver, said in a press briefing. Chemotherapy is still considered standard of care in the first-line setting.
Main results showed that compared with chemotherapy (carboplatin and nab-paclitaxel) alone, the combination of atezolizumab and chemotherapy reduced the risk of progression-free survival events by 29%, prolonging median time to an event by about a month. Findings were similar regardless of the level of PD-L1 positivity, although reduction in events was greatest for patients whose tumors were highly positive.
Median overall survival was about 14 months in each arm, with no significant difference, although results are not yet mature.
“IMpower131 data show that patients with advanced squamous NSCLC benefit more from initial treatment with atezolizumab plus chemotherapy than from chemotherapy alone,” Dr. Jotte summarized. The combination “has a manageable safety profile consistent with known safety risks of the individual therapies, with no new safety signals identified.”
The investigators are continuing to follow overall survival, with the next interim analysis expected to occur later this year. “In the IMpower131 study, patients were not allowed to cross over. However, among patients who were monitored and followed for subsequent therapy, nearly half went on to receive immuno-oncologic therapies beyond the study, so that will likely taint the overall survival curves,” he noted.
Patients receiving chemotherapy for advanced lung cancer are devastated when told that their disease has progressed, he commented. “What we see with the results of this study is that we can actually double the chance that they don’t have to hear that bad news in the first year of treatment.”
“We hope that the results seen with progression-free survival translate to improved overall survival. If and when that is shown, I think we will clearly have a new standard of care for the front-line treatment of squamous cell NSCLC,” concluded Dr. Graham, who is also medical director at the Levine Cancer Institute in Charlotte, N.C.
Study details
With a median follow-up of 17.1 months in IMpower131, median progression-free survival was 5.6 months with chemotherapy alone and 6.3 months when atezolizumab was added to chemotherapy (hazard ratio, 0.71; P = .0001).
There was a doubling of the 12-month progression-free survival rate, from 12.0% to 24.7%, Dr. Jotte reported.
Atezolizumab improved progression-free survival across levels of PD-L1 expression, but benefit was most pronounced in patients with tumors having a high level of this biomarker (hazard ratio, 0.44).
Findings were similar for response, with a higher overall response rate seen with atezolizumab plus chemotherapy versus chemotherapy alone (49% vs. 41%) and greatest difference in the subgroup whose tumors were highly PD-L1 positive (60% vs. 33%). Median duration of response was 7.2 months with the immunotherapy and 5.2 months without it.
Interim overall survival results showed that patients lived a median of 14.0 months with atezolizumab plus chemotherapy and 13.9 months with chemotherapy alone (hazard ratio, 0.96; P = .6931).
Data from a third arm of the IMpower131 trial, in which atezolizumab was added to carboplatin plus paclitaxel, have not reached a point where statistical analyses can be done, according to Dr. Jotte.
A related phase 3 trial, IMpower150, is testing addition of atezolizumab to chemotherapy, with or without bevacizumab, as first-line therapy for metastatic nonsquamous NSCLC. Investigators will be reporting results at the meeting for both overall survival (abstract 9002) and patient-reported outcomes (abstract 9047).
Dr. Jotte disclosed that he is on the speakers’ bureau for Bristol-Myers Squibb, and that he receives travel, accommodations, and/or expenses, as well as honoraria from Bristol-Myers Squibb. The study received funding from F. Hoffmann-La Roche Ltd.
SOURCE: Jotte et al. ASCO 2018 Abstract LBA9000.
REPORTING FROM ASCO 2018
Key clinical point: .
Major finding: Compared with chemotherapy alone, chemotherapy plus atezolizumab prolonged median progression-free survival from 5.6 to 6.3 months (hazard ratio, 0.71; P = .0001).
Study details: A phase 3 randomized, controlled trial among 1,021 all-comer (PD-L1–unselected), chemotherapy-naïve patients with stage IV squamous NSCLC (IMpower131 trial).
Disclosures: Dr. Jotte disclosed that he is on the speakers’ bureau for Bristol-Myers Squibb, and that he receives travel, accommodations, and/or expenses, as well as honoraria from Bristol-Myers Squibb. The study received funding from F. Hoffmann-La Roche Ltd.
Source: Jotte et al. ASCO 2018 Abstract LBA9000.
Ruxolitinib overcame lenalidomide resistance in myeloma
based on phase I trial results presented at the annual meeting of the American Society of Clinical Oncology (ASCO).
The clinical trial is the first to demonstrate the activity of a JAK inhibitor in the treatment of myeloma patients, according to investigator James R. Berenson, MD, medical and scientific director for the Institute for Myeloma & Bone Cancer Research (IMBCR), West Hollywood, Calif.
“These promising results have led to the expansion of the current clinical trial and provide the basis for exploration of this and other JAK inhibitor-containing combinations for treating patients with myeloma and other malignant diseases,” he added.
The dose-escalation study enrolled 28 patients with relapsed/refractory multiple myeloma who had previous treatment with lenalidomide/steroids and a proteasome inhibitor. Subjects received ruxolitinib twice daily continuously, lenalidomide daily on days 1-21 of a 28-day cycle, and methylprednisolone orally every other day. A traditional 3+3 dose escalation design was used to enroll subjects in four cohorts. In DL0, patients received ruxolitinib 5 mg, lenalidomide 5 mg, and methylprednisolone 40 mg. In DL+1 and +2, both doses of lenalidomide and methylprednisolone remained unchanged, and ruxolitinib was escalated to 10 and 15 mg, respectively. In DL+3, lenalidomide was escalated to 10 mg with methylprednisolone unchanged and ruxolitinib at 15 mg. A total of 19 patients were treated at the highest dose level, which was ruxolitinib 15 mg twice daily on days 1-28, lenalidomide 10 mg daily on days 1-21, and methylprednisolone 40 mg every other day.
The overall response rate was 39% (10 of 26 evaluable patients), Dr. Berenson reported. The clinical benefit rate was 50% (13 of 26 patients), with a median duration of response of 5.6 months in that group.
There were no dose-limiting toxicities. Grade 3 toxicities reported included thrombocytopenia in 11% (3 patients, gastrointestinal bleeding in 11% (3 patients), and anemia in 7% (2 patients).
These results are encouraging, though challenges remain, said Craig Hofmeister, MD, MPH, of Winship Cancer Institute, Emory University, Atlanta.
“Clearly in these patients who are 100% lenalidomide refractory, the overall response rate of anything greater than or close to 20, 30, 40% is very appealing,” Dr. Hofmeister said in an ASCO presentation discussing the results of this trial.
The usual rationale for JAK inhibition is targeting of the bone microenvironment, but the microenvironment is a formidable opponent, Dr. Hofmeister said in his presentation.
“That’s an uphill battle,” he said. “There is an upcoming carfilzomib and ruxolitinib trial in multiple myeloma moving forward, and I’d be excited to see” the results.
The study (NCT03110822) was sponsored by Oncotherapeutics in collaboration with Incyte, the maker of ruxolitinib (Jakafi). Dr. Berenson, the presenting author, had disclosures related to Incyte, as well as Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and OncoTracker.
SOURCE: Berenson JR, et al. J Clin Oncol 36, 2018 (suppl; abstr 8005).
based on phase I trial results presented at the annual meeting of the American Society of Clinical Oncology (ASCO).
The clinical trial is the first to demonstrate the activity of a JAK inhibitor in the treatment of myeloma patients, according to investigator James R. Berenson, MD, medical and scientific director for the Institute for Myeloma & Bone Cancer Research (IMBCR), West Hollywood, Calif.
“These promising results have led to the expansion of the current clinical trial and provide the basis for exploration of this and other JAK inhibitor-containing combinations for treating patients with myeloma and other malignant diseases,” he added.
The dose-escalation study enrolled 28 patients with relapsed/refractory multiple myeloma who had previous treatment with lenalidomide/steroids and a proteasome inhibitor. Subjects received ruxolitinib twice daily continuously, lenalidomide daily on days 1-21 of a 28-day cycle, and methylprednisolone orally every other day. A traditional 3+3 dose escalation design was used to enroll subjects in four cohorts. In DL0, patients received ruxolitinib 5 mg, lenalidomide 5 mg, and methylprednisolone 40 mg. In DL+1 and +2, both doses of lenalidomide and methylprednisolone remained unchanged, and ruxolitinib was escalated to 10 and 15 mg, respectively. In DL+3, lenalidomide was escalated to 10 mg with methylprednisolone unchanged and ruxolitinib at 15 mg. A total of 19 patients were treated at the highest dose level, which was ruxolitinib 15 mg twice daily on days 1-28, lenalidomide 10 mg daily on days 1-21, and methylprednisolone 40 mg every other day.
The overall response rate was 39% (10 of 26 evaluable patients), Dr. Berenson reported. The clinical benefit rate was 50% (13 of 26 patients), with a median duration of response of 5.6 months in that group.
There were no dose-limiting toxicities. Grade 3 toxicities reported included thrombocytopenia in 11% (3 patients, gastrointestinal bleeding in 11% (3 patients), and anemia in 7% (2 patients).
These results are encouraging, though challenges remain, said Craig Hofmeister, MD, MPH, of Winship Cancer Institute, Emory University, Atlanta.
“Clearly in these patients who are 100% lenalidomide refractory, the overall response rate of anything greater than or close to 20, 30, 40% is very appealing,” Dr. Hofmeister said in an ASCO presentation discussing the results of this trial.
The usual rationale for JAK inhibition is targeting of the bone microenvironment, but the microenvironment is a formidable opponent, Dr. Hofmeister said in his presentation.
“That’s an uphill battle,” he said. “There is an upcoming carfilzomib and ruxolitinib trial in multiple myeloma moving forward, and I’d be excited to see” the results.
The study (NCT03110822) was sponsored by Oncotherapeutics in collaboration with Incyte, the maker of ruxolitinib (Jakafi). Dr. Berenson, the presenting author, had disclosures related to Incyte, as well as Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and OncoTracker.
SOURCE: Berenson JR, et al. J Clin Oncol 36, 2018 (suppl; abstr 8005).
based on phase I trial results presented at the annual meeting of the American Society of Clinical Oncology (ASCO).
The clinical trial is the first to demonstrate the activity of a JAK inhibitor in the treatment of myeloma patients, according to investigator James R. Berenson, MD, medical and scientific director for the Institute for Myeloma & Bone Cancer Research (IMBCR), West Hollywood, Calif.
“These promising results have led to the expansion of the current clinical trial and provide the basis for exploration of this and other JAK inhibitor-containing combinations for treating patients with myeloma and other malignant diseases,” he added.
The dose-escalation study enrolled 28 patients with relapsed/refractory multiple myeloma who had previous treatment with lenalidomide/steroids and a proteasome inhibitor. Subjects received ruxolitinib twice daily continuously, lenalidomide daily on days 1-21 of a 28-day cycle, and methylprednisolone orally every other day. A traditional 3+3 dose escalation design was used to enroll subjects in four cohorts. In DL0, patients received ruxolitinib 5 mg, lenalidomide 5 mg, and methylprednisolone 40 mg. In DL+1 and +2, both doses of lenalidomide and methylprednisolone remained unchanged, and ruxolitinib was escalated to 10 and 15 mg, respectively. In DL+3, lenalidomide was escalated to 10 mg with methylprednisolone unchanged and ruxolitinib at 15 mg. A total of 19 patients were treated at the highest dose level, which was ruxolitinib 15 mg twice daily on days 1-28, lenalidomide 10 mg daily on days 1-21, and methylprednisolone 40 mg every other day.
The overall response rate was 39% (10 of 26 evaluable patients), Dr. Berenson reported. The clinical benefit rate was 50% (13 of 26 patients), with a median duration of response of 5.6 months in that group.
There were no dose-limiting toxicities. Grade 3 toxicities reported included thrombocytopenia in 11% (3 patients, gastrointestinal bleeding in 11% (3 patients), and anemia in 7% (2 patients).
These results are encouraging, though challenges remain, said Craig Hofmeister, MD, MPH, of Winship Cancer Institute, Emory University, Atlanta.
“Clearly in these patients who are 100% lenalidomide refractory, the overall response rate of anything greater than or close to 20, 30, 40% is very appealing,” Dr. Hofmeister said in an ASCO presentation discussing the results of this trial.
The usual rationale for JAK inhibition is targeting of the bone microenvironment, but the microenvironment is a formidable opponent, Dr. Hofmeister said in his presentation.
“That’s an uphill battle,” he said. “There is an upcoming carfilzomib and ruxolitinib trial in multiple myeloma moving forward, and I’d be excited to see” the results.
The study (NCT03110822) was sponsored by Oncotherapeutics in collaboration with Incyte, the maker of ruxolitinib (Jakafi). Dr. Berenson, the presenting author, had disclosures related to Incyte, as well as Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and OncoTracker.
SOURCE: Berenson JR, et al. J Clin Oncol 36, 2018 (suppl; abstr 8005).
REPORTING FROM ASCO 2018
Key clinical point: The JAK 1/2 inhibitor ruxolitinib, in combination with lenalidomide and methylprednisolone, overcame resistance to lenalidomide in about half of heavily pre-treated patients with relapsed/refractory multiple myeloma in a phase I trial.
Major finding: The overall response rate was 39%, and the clinical benefit rate was 50% (13 of 26 patients).
Study details: A phase 1 study including 28 patients with relapsed/refractory multiple myeloma who had previous treatment with lenalidomide/steroids and a proteasome inhibitor.
Disclosures: Dr. Berenson, the presenting author, had disclosures related to Amgen, Bristol-Myers Squibb, Celgene, Incyte, Janssen, Takeda, and OncoTracker.
Source: Berenson JR, et al. J Clin Oncol 36, 2018 (suppl; abstr 8005).
App monitoring improves quality of IBD care
WASHINGTON – in a single-center randomized study with 320 patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Based on this success, the app will soon be made available to all of the roughly 5,000 inflammatory bowel disease (IBD) patients managed at Mount Sinai Medical Center in New York as well as IBD patients at several other North American centers that plan to adopt the app, Ashish Atreja, MD, said at the annual Digestive Disease Week.®
Home monitoring of IBD patients “is feasible with high adoption,” said Dr. Atreja, a gastroenterologist at Mount Sinai who directs the Sinai AppLab. The 162 IBD patients randomized to regularly use the HealthPROMISE app had their quality-of-care metric rise from 50% at baseline to 84% after an average follow-up of 575 days (19 months), a statistically significant improvement over the 158 control patients whose metric rose from 50% to 65% for the study’s primary endpoint, he reported. The results also showed a trend toward improved quality of life among the patients using the HealthPROMISE app, compared with the controls, who used an IBD educational app that produced less patient engagement than did the HealthPROMISE app, Dr Atreja said.
Dr. Atreja and his associates modeled the app on remote monitoring methods developed for patients with other types of chronic disease, such as diabetes and heart failure.
“You can’t provide proactive IBD care without remote monitoring,” Dr. Atreja explained in a video interview. “Reactive care is not best practice anymore. The only way to do treat-to-target is with remote monitoring.”
Care coordinators monitor the entries that IBD patients send in via the app. Dr. Atreja estimated that about five care coordinators will be able to track the inputs from the roughly 5,000 IBD patients at Mount Sinai who will soon begin using the app. The financial feasibility of this approach depends in part on the $45/patient per month reimbursement that U.S. health insurers now provide to centers that run remote monitoring programs, he said.
“The direction for managing chronic diseases is increasingly looking at home monitoring as a way to streamline costs and improve patient care,” commented Gil Y. Melmed, MD, director of Clinical Inflammatory Bowel Disease at Cedars-Sinai Medical Center in Los Angeles. The results that Dr. Atreja reported came from “a highly selected population that was well educated and largely white.” The study needs replication in different patient groups to establish its reproducibility and generalizability, Dr. Melmed said in an interview.
Dr. Melmed had no relevant disclosures.
mzoler@mdedge.com
On Twitter @mitchelzoler
SOURCE: Atreja A et al. Digestive Disease Week 2018 abstract 17.
*This story was updated on June 7, 2018.
WASHINGTON – in a single-center randomized study with 320 patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Based on this success, the app will soon be made available to all of the roughly 5,000 inflammatory bowel disease (IBD) patients managed at Mount Sinai Medical Center in New York as well as IBD patients at several other North American centers that plan to adopt the app, Ashish Atreja, MD, said at the annual Digestive Disease Week.®
Home monitoring of IBD patients “is feasible with high adoption,” said Dr. Atreja, a gastroenterologist at Mount Sinai who directs the Sinai AppLab. The 162 IBD patients randomized to regularly use the HealthPROMISE app had their quality-of-care metric rise from 50% at baseline to 84% after an average follow-up of 575 days (19 months), a statistically significant improvement over the 158 control patients whose metric rose from 50% to 65% for the study’s primary endpoint, he reported. The results also showed a trend toward improved quality of life among the patients using the HealthPROMISE app, compared with the controls, who used an IBD educational app that produced less patient engagement than did the HealthPROMISE app, Dr Atreja said.
Dr. Atreja and his associates modeled the app on remote monitoring methods developed for patients with other types of chronic disease, such as diabetes and heart failure.
“You can’t provide proactive IBD care without remote monitoring,” Dr. Atreja explained in a video interview. “Reactive care is not best practice anymore. The only way to do treat-to-target is with remote monitoring.”
Care coordinators monitor the entries that IBD patients send in via the app. Dr. Atreja estimated that about five care coordinators will be able to track the inputs from the roughly 5,000 IBD patients at Mount Sinai who will soon begin using the app. The financial feasibility of this approach depends in part on the $45/patient per month reimbursement that U.S. health insurers now provide to centers that run remote monitoring programs, he said.
“The direction for managing chronic diseases is increasingly looking at home monitoring as a way to streamline costs and improve patient care,” commented Gil Y. Melmed, MD, director of Clinical Inflammatory Bowel Disease at Cedars-Sinai Medical Center in Los Angeles. The results that Dr. Atreja reported came from “a highly selected population that was well educated and largely white.” The study needs replication in different patient groups to establish its reproducibility and generalizability, Dr. Melmed said in an interview.
Dr. Melmed had no relevant disclosures.
mzoler@mdedge.com
On Twitter @mitchelzoler
SOURCE: Atreja A et al. Digestive Disease Week 2018 abstract 17.
*This story was updated on June 7, 2018.
WASHINGTON – in a single-center randomized study with 320 patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Based on this success, the app will soon be made available to all of the roughly 5,000 inflammatory bowel disease (IBD) patients managed at Mount Sinai Medical Center in New York as well as IBD patients at several other North American centers that plan to adopt the app, Ashish Atreja, MD, said at the annual Digestive Disease Week.®
Home monitoring of IBD patients “is feasible with high adoption,” said Dr. Atreja, a gastroenterologist at Mount Sinai who directs the Sinai AppLab. The 162 IBD patients randomized to regularly use the HealthPROMISE app had their quality-of-care metric rise from 50% at baseline to 84% after an average follow-up of 575 days (19 months), a statistically significant improvement over the 158 control patients whose metric rose from 50% to 65% for the study’s primary endpoint, he reported. The results also showed a trend toward improved quality of life among the patients using the HealthPROMISE app, compared with the controls, who used an IBD educational app that produced less patient engagement than did the HealthPROMISE app, Dr Atreja said.
Dr. Atreja and his associates modeled the app on remote monitoring methods developed for patients with other types of chronic disease, such as diabetes and heart failure.
“You can’t provide proactive IBD care without remote monitoring,” Dr. Atreja explained in a video interview. “Reactive care is not best practice anymore. The only way to do treat-to-target is with remote monitoring.”
Care coordinators monitor the entries that IBD patients send in via the app. Dr. Atreja estimated that about five care coordinators will be able to track the inputs from the roughly 5,000 IBD patients at Mount Sinai who will soon begin using the app. The financial feasibility of this approach depends in part on the $45/patient per month reimbursement that U.S. health insurers now provide to centers that run remote monitoring programs, he said.
“The direction for managing chronic diseases is increasingly looking at home monitoring as a way to streamline costs and improve patient care,” commented Gil Y. Melmed, MD, director of Clinical Inflammatory Bowel Disease at Cedars-Sinai Medical Center in Los Angeles. The results that Dr. Atreja reported came from “a highly selected population that was well educated and largely white.” The study needs replication in different patient groups to establish its reproducibility and generalizability, Dr. Melmed said in an interview.
Dr. Melmed had no relevant disclosures.
mzoler@mdedge.com
On Twitter @mitchelzoler
SOURCE: Atreja A et al. Digestive Disease Week 2018 abstract 17.
*This story was updated on June 7, 2018.
REPORTING FROM DDW 2018
Key clinical point: Regular remote monitoring of IBD patients improved the medical care they received.
Major finding: Quality of care rose from 50% at baseline to 84% in app-monitored patients and to 65% in controls.
Study details: A single-center randomized study with 320 IBD patients.
Disclosures: The study had no commercial funding. Dr. Atreja had no disclosures.
Source: Atreja A et al. Digestive Disease Week 2018 abstract 17.
Timely dermatomyositis diagnosis, treatment remain elusive
ORLANDO – There was a median 1-year delay between the onset of symptoms and diagnosis of classic dermatomyositis, and a 17-month delay before diagnosis of amyopathic dermatomyositis, based on a review of 232 dermatomyositis patients seen at the University of Pennsylvania, Philadelphia.
Just 103 (44.4%) patients were diagnosed with dermatomyositis (DM) right out of the gate. Among the other 129, 48 (37.2%) were diagnosed with lupus, 38 (29.5%) with undifferentiated connective tissue disease, 10 (7.8%) went undiagnosed, and 33 (25.5%) were diagnosed with rosacea, psoriasis, rheumatoid arthritis, fibromyalgia, lichen planus, and a number of other conditions. By the time the DM diagnosis was finally confirmed, almost every patient had Gottron’s papules or sign.
Misdiagnosis of dermatomyositis (DM) is nothing new, but the study brings home just how common the problem is, even at a major academic medical institution.
One of the take homes is that , and remain vigilant for erythema on the lateral thighs or nasolabial fold, Gottron’s papules, and other diagnostic giveaways, the researchers said.
Interface dermatitis, in particular, can’t be relied on to differentiate the conditions. A better option is checking for lupus bands and membrane attack complexes on direct immunofluorescence.
There’s also just not enough awareness that dermatomyositis can present without the classic muscle symptoms and findings, i.e. clinically amyopathic DM. While 49 of 120 patients with classic dermatomyositis (40.8%) were misdiagnosed or undiagnosed in the study, the number rose to 80 of 112 (71.4%) among amyopathic patients.
“We saw that there was a much higher rate of misdiagnosis in patients who didn’t have any muscle disease. We have to raise awareness that amyopathic dermatomyositis is a very prevalent condition,” Dr. Patel said at the International Conference on Cutaneous Lupus Erythematosus.
“There might be some level of subclinical muscle activity where, if you did an MRI, you might see inflammation, but the patient doesn’t report any symptoms. There are also patients that don’t have any muscle findings on MRI, or elevated muscle enzymes, but still have the skin findings,” he said.
Perhaps the markedly increased risk of cancer in DM, especially within a year or 2 of symptom onset, is the strongest argument for earlier diagnosis. “There’s also a risk of interstitial lung disease, so making sure that you’re getting pulmonary function tests and age-appropriate malignancy screening in a timely fashion is very important,” Dr. Patel said.
Also, although many of the initial treatments for DM – sun protection and topical steroids and calcineurin inhibitors, for instance – are the same as for cutaneous lupus, medications like mycophenolate mofetil and methotrexate are used more readily. The sooner DM is recognized for what it is, the sooner patients can get relief, he said.
Almost all the patients were white women. The majority were 40-80 years old.
There was no industry funding for the work, and Dr. Patel didn’t have any disclosures.
SOURCE: da Silva DM et al. Presented at the 2018 International Conference on Cutaneous Lupus Erythematosus
ORLANDO – There was a median 1-year delay between the onset of symptoms and diagnosis of classic dermatomyositis, and a 17-month delay before diagnosis of amyopathic dermatomyositis, based on a review of 232 dermatomyositis patients seen at the University of Pennsylvania, Philadelphia.
Just 103 (44.4%) patients were diagnosed with dermatomyositis (DM) right out of the gate. Among the other 129, 48 (37.2%) were diagnosed with lupus, 38 (29.5%) with undifferentiated connective tissue disease, 10 (7.8%) went undiagnosed, and 33 (25.5%) were diagnosed with rosacea, psoriasis, rheumatoid arthritis, fibromyalgia, lichen planus, and a number of other conditions. By the time the DM diagnosis was finally confirmed, almost every patient had Gottron’s papules or sign.
Misdiagnosis of dermatomyositis (DM) is nothing new, but the study brings home just how common the problem is, even at a major academic medical institution.
One of the take homes is that , and remain vigilant for erythema on the lateral thighs or nasolabial fold, Gottron’s papules, and other diagnostic giveaways, the researchers said.
Interface dermatitis, in particular, can’t be relied on to differentiate the conditions. A better option is checking for lupus bands and membrane attack complexes on direct immunofluorescence.
There’s also just not enough awareness that dermatomyositis can present without the classic muscle symptoms and findings, i.e. clinically amyopathic DM. While 49 of 120 patients with classic dermatomyositis (40.8%) were misdiagnosed or undiagnosed in the study, the number rose to 80 of 112 (71.4%) among amyopathic patients.
“We saw that there was a much higher rate of misdiagnosis in patients who didn’t have any muscle disease. We have to raise awareness that amyopathic dermatomyositis is a very prevalent condition,” Dr. Patel said at the International Conference on Cutaneous Lupus Erythematosus.
“There might be some level of subclinical muscle activity where, if you did an MRI, you might see inflammation, but the patient doesn’t report any symptoms. There are also patients that don’t have any muscle findings on MRI, or elevated muscle enzymes, but still have the skin findings,” he said.
Perhaps the markedly increased risk of cancer in DM, especially within a year or 2 of symptom onset, is the strongest argument for earlier diagnosis. “There’s also a risk of interstitial lung disease, so making sure that you’re getting pulmonary function tests and age-appropriate malignancy screening in a timely fashion is very important,” Dr. Patel said.
Also, although many of the initial treatments for DM – sun protection and topical steroids and calcineurin inhibitors, for instance – are the same as for cutaneous lupus, medications like mycophenolate mofetil and methotrexate are used more readily. The sooner DM is recognized for what it is, the sooner patients can get relief, he said.
Almost all the patients were white women. The majority were 40-80 years old.
There was no industry funding for the work, and Dr. Patel didn’t have any disclosures.
SOURCE: da Silva DM et al. Presented at the 2018 International Conference on Cutaneous Lupus Erythematosus
ORLANDO – There was a median 1-year delay between the onset of symptoms and diagnosis of classic dermatomyositis, and a 17-month delay before diagnosis of amyopathic dermatomyositis, based on a review of 232 dermatomyositis patients seen at the University of Pennsylvania, Philadelphia.
Just 103 (44.4%) patients were diagnosed with dermatomyositis (DM) right out of the gate. Among the other 129, 48 (37.2%) were diagnosed with lupus, 38 (29.5%) with undifferentiated connective tissue disease, 10 (7.8%) went undiagnosed, and 33 (25.5%) were diagnosed with rosacea, psoriasis, rheumatoid arthritis, fibromyalgia, lichen planus, and a number of other conditions. By the time the DM diagnosis was finally confirmed, almost every patient had Gottron’s papules or sign.
Misdiagnosis of dermatomyositis (DM) is nothing new, but the study brings home just how common the problem is, even at a major academic medical institution.
One of the take homes is that , and remain vigilant for erythema on the lateral thighs or nasolabial fold, Gottron’s papules, and other diagnostic giveaways, the researchers said.
Interface dermatitis, in particular, can’t be relied on to differentiate the conditions. A better option is checking for lupus bands and membrane attack complexes on direct immunofluorescence.
There’s also just not enough awareness that dermatomyositis can present without the classic muscle symptoms and findings, i.e. clinically amyopathic DM. While 49 of 120 patients with classic dermatomyositis (40.8%) were misdiagnosed or undiagnosed in the study, the number rose to 80 of 112 (71.4%) among amyopathic patients.
“We saw that there was a much higher rate of misdiagnosis in patients who didn’t have any muscle disease. We have to raise awareness that amyopathic dermatomyositis is a very prevalent condition,” Dr. Patel said at the International Conference on Cutaneous Lupus Erythematosus.
“There might be some level of subclinical muscle activity where, if you did an MRI, you might see inflammation, but the patient doesn’t report any symptoms. There are also patients that don’t have any muscle findings on MRI, or elevated muscle enzymes, but still have the skin findings,” he said.
Perhaps the markedly increased risk of cancer in DM, especially within a year or 2 of symptom onset, is the strongest argument for earlier diagnosis. “There’s also a risk of interstitial lung disease, so making sure that you’re getting pulmonary function tests and age-appropriate malignancy screening in a timely fashion is very important,” Dr. Patel said.
Also, although many of the initial treatments for DM – sun protection and topical steroids and calcineurin inhibitors, for instance – are the same as for cutaneous lupus, medications like mycophenolate mofetil and methotrexate are used more readily. The sooner DM is recognized for what it is, the sooner patients can get relief, he said.
Almost all the patients were white women. The majority were 40-80 years old.
There was no industry funding for the work, and Dr. Patel didn’t have any disclosures.
SOURCE: da Silva DM et al. Presented at the 2018 International Conference on Cutaneous Lupus Erythematosus
REPORTING FROM ICCLE 2018
Key clinical point: Clinicians need to do a better job of catching DM early.
Major finding: It took a median of 12.2 months after the start of symptoms to diagnose classic dermatomyositis, and 17.1 months to diagnose amyopathic dermatomyositis.
Study details: Review of 232 patients
Disclosures: There was no industry funding, and the presenter didn’t have any disclosures.
Source: da Silva DM et al. Presented at the 2018 International Conference on Cutaneous Lupus Erythematosus