For patients undergoing elective permanent colostomy, prophylactic augmentation of the abdominal wall using mesh at the ostomy site prevents the development of parastomal hernia, according to a report published in the April issue of Annals of Surgery.

The incidence of parastomal hernia is expected to rise because of the increasing number of cancer patients surviving with a colostomy, and the rising number of obese patients who have increased tension on the abdominal wall because of their elevated intra-abdominal pressure and larger abdominal radius. Researchers in the Netherlands performed a prospective randomized study, the PREVENT trial, to assess whether augmenting the abdominal wall at the ostomy site, using a lightweight mesh, would be safe, feasible, and effective at preventing parastomal hernia. They reported their findings after 1 year of follow-up; the study will continue until longer-term results are available at 5 years.

castillodominici/Thinkstock

This study was supported by Canisius Wilhelmina Hospital’s surgery research fund, the Netherlands Organization for Health Research and Development, and Covidien/Medtronic. Dr. Brandsma and his associates reported having no relevant financial disclosures.

For patients undergoing elective permanent colostomy, prophylactic augmentation of the abdominal wall using mesh at the ostomy site prevents the development of parastomal hernia, according to a report published in the April issue of Annals of Surgery.

The incidence of parastomal hernia is expected to rise because of the increasing number of cancer patients surviving with a colostomy, and the rising number of obese patients who have increased tension on the abdominal wall because of their elevated intra-abdominal pressure and larger abdominal radius. Researchers in the Netherlands performed a prospective randomized study, the PREVENT trial, to assess whether augmenting the abdominal wall at the ostomy site, using a lightweight mesh, would be safe, feasible, and effective at preventing parastomal hernia. They reported their findings after 1 year of follow-up; the study will continue until longer-term results are available at 5 years.

castillodominici/Thinkstock

This study was supported by Canisius Wilhelmina Hospital’s surgery research fund, the Netherlands Organization for Health Research and Development, and Covidien/Medtronic. Dr. Brandsma and his associates reported having no relevant financial disclosures.

For patients undergoing elective permanent colostomy, prophylactic augmentation of the abdominal wall using mesh at the ostomy site prevents the development of parastomal hernia, according to a report published in the April issue of Annals of Surgery.

The incidence of parastomal hernia is expected to rise because of the increasing number of cancer patients surviving with a colostomy, and the rising number of obese patients who have increased tension on the abdominal wall because of their elevated intra-abdominal pressure and larger abdominal radius. Researchers in the Netherlands performed a prospective randomized study, the PREVENT trial, to assess whether augmenting the abdominal wall at the ostomy site, using a lightweight mesh, would be safe, feasible, and effective at preventing parastomal hernia. They reported their findings after 1 year of follow-up; the study will continue until longer-term results are available at 5 years.

castillodominici/Thinkstock

This study was supported by Canisius Wilhelmina Hospital’s surgery research fund, the Netherlands Organization for Health Research and Development, and Covidien/Medtronic. Dr. Brandsma and his associates reported having no relevant financial disclosures.

FROM SEMINARS IN ARTHRITIS & RHEUMATISM

Around two-thirds of patients with severe or refractory sarcoidosis show a significant clinical response to tumor necrosis factor (TNF) antagonists, according to findings from a retrospective, multicenter cohort study.

Biologic agents targeting TNF, such as etanercept, infliximab, and adalimumab, have been introduced as a third-line option for patients with disease that is refractory to other treatments. However, Yvan Jamilloux, MD, of the Hospices Civils de Lyon (France) and his coauthors reported that there are still insufficient data available on efficacy and safety of these drugs in the context of sarcoidosis.

Dr. Jamilloux and his colleagues analyzed data from 132 sarcoidosis patients who received TNF antagonists, 122 (92%) of whom had severe sarcoidosis (Semin Arthritis Rheum. 2017 Mar 8. doi: 10.1016/j.semarthrit.2017.03.005).

Overall, 64% of patients showed clinical improvements in response to TNF antagonists; 18% had a complete response, and 46% had a partial response. However, 33 (25%) patients showed no change, and 14 (11%) had continued disease progression despite treatment with TNF antagonists. In another 16 patients who received a second TNF antagonist, 10 (63%) had a complete or partial clinical response. The investigators could find no differences in response between anti-TNF agents or between monotherapy and a combination with an immunosuppressant.

Pulmonary involvement was associated with a significantly lower clinical response, but none of the other factors examined in a multivariate analysis (sex, age, ethnicity, organ involvement, disease duration, steroid dosage, or prior immunosuppressant use) distinguished responders and nonresponders.

The authors noted that these response rates were lower than those seen in the literature and suggested this may be attributable to the multicenter design, more patients with longer-lasting and more refractory disease, and longer times under biologic therapy (median 12 months).

The researchers reported significant improvements in central nervous system, peripheral nervous system, heart, skin, and upper respiratory tract involvements based on declines in Extrapulmonary Physician Organ Severity Tool (ePOST) scores. There were also improvements in the eye, muscle, and lung, but these were not statistically significant.

TNF-antagonist therapy was associated with a high rate of adverse events. Around half of all patients (52%) experienced adverse events, such as pneumonia, urinary tract infections, bacterial sepsis, and herpes zoster. In 31 patients (23%), these led to treatment cessation.

Nine patients also had severe allergic reactions, four had paradoxical granulomatous reactions, three developed neutralizing antibodies against anti-TNF agents, two patients had demyelinating lesions, and one had a serum sickness-like reaction. All of these events led to discontinuation.

Overall, 128 (97%) of the patients in the study had received corticosteroids as first-line therapy, and 125 (95%) had received at least one second-line immunosuppressive drug over a median duration of 16 months. Most were treated with infliximab (91%) as the first-line TNF antagonist, followed by adalimumab (6%), etanercept (2%), and certolizumab pegol (1%).

Treatment with TNF antagonists was associated with significant reductions in corticosteroid use; the mean daily prednisone dose decreased from 23 mg/day to 11 mg/day over the median 20.5-month follow-up. This was seen even in the 33 patients who showed no change in their disease course after TNF-antagonist therapy.

No conflicts of interest were declared.

rhnews@frontlinemedcom.com

FROM SEMINARS IN ARTHRITIS & RHEUMATISM

Around two-thirds of patients with severe or refractory sarcoidosis show a significant clinical response to tumor necrosis factor (TNF) antagonists, according to findings from a retrospective, multicenter cohort study.

Biologic agents targeting TNF, such as etanercept, infliximab, and adalimumab, have been introduced as a third-line option for patients with disease that is refractory to other treatments. However, Yvan Jamilloux, MD, of the Hospices Civils de Lyon (France) and his coauthors reported that there are still insufficient data available on efficacy and safety of these drugs in the context of sarcoidosis.

Dr. Jamilloux and his colleagues analyzed data from 132 sarcoidosis patients who received TNF antagonists, 122 (92%) of whom had severe sarcoidosis (Semin Arthritis Rheum. 2017 Mar 8. doi: 10.1016/j.semarthrit.2017.03.005).

Overall, 64% of patients showed clinical improvements in response to TNF antagonists; 18% had a complete response, and 46% had a partial response. However, 33 (25%) patients showed no change, and 14 (11%) had continued disease progression despite treatment with TNF antagonists. In another 16 patients who received a second TNF antagonist, 10 (63%) had a complete or partial clinical response. The investigators could find no differences in response between anti-TNF agents or between monotherapy and a combination with an immunosuppressant.

Pulmonary involvement was associated with a significantly lower clinical response, but none of the other factors examined in a multivariate analysis (sex, age, ethnicity, organ involvement, disease duration, steroid dosage, or prior immunosuppressant use) distinguished responders and nonresponders.

The authors noted that these response rates were lower than those seen in the literature and suggested this may be attributable to the multicenter design, more patients with longer-lasting and more refractory disease, and longer times under biologic therapy (median 12 months).

The researchers reported significant improvements in central nervous system, peripheral nervous system, heart, skin, and upper respiratory tract involvements based on declines in Extrapulmonary Physician Organ Severity Tool (ePOST) scores. There were also improvements in the eye, muscle, and lung, but these were not statistically significant.

TNF-antagonist therapy was associated with a high rate of adverse events. Around half of all patients (52%) experienced adverse events, such as pneumonia, urinary tract infections, bacterial sepsis, and herpes zoster. In 31 patients (23%), these led to treatment cessation.

Nine patients also had severe allergic reactions, four had paradoxical granulomatous reactions, three developed neutralizing antibodies against anti-TNF agents, two patients had demyelinating lesions, and one had a serum sickness-like reaction. All of these events led to discontinuation.

Overall, 128 (97%) of the patients in the study had received corticosteroids as first-line therapy, and 125 (95%) had received at least one second-line immunosuppressive drug over a median duration of 16 months. Most were treated with infliximab (91%) as the first-line TNF antagonist, followed by adalimumab (6%), etanercept (2%), and certolizumab pegol (1%).

Treatment with TNF antagonists was associated with significant reductions in corticosteroid use; the mean daily prednisone dose decreased from 23 mg/day to 11 mg/day over the median 20.5-month follow-up. This was seen even in the 33 patients who showed no change in their disease course after TNF-antagonist therapy.

No conflicts of interest were declared.

rhnews@frontlinemedcom.com

FROM SEMINARS IN ARTHRITIS & RHEUMATISM

Around two-thirds of patients with severe or refractory sarcoidosis show a significant clinical response to tumor necrosis factor (TNF) antagonists, according to findings from a retrospective, multicenter cohort study.

Biologic agents targeting TNF, such as etanercept, infliximab, and adalimumab, have been introduced as a third-line option for patients with disease that is refractory to other treatments. However, Yvan Jamilloux, MD, of the Hospices Civils de Lyon (France) and his coauthors reported that there are still insufficient data available on efficacy and safety of these drugs in the context of sarcoidosis.

Dr. Jamilloux and his colleagues analyzed data from 132 sarcoidosis patients who received TNF antagonists, 122 (92%) of whom had severe sarcoidosis (Semin Arthritis Rheum. 2017 Mar 8. doi: 10.1016/j.semarthrit.2017.03.005).

Overall, 64% of patients showed clinical improvements in response to TNF antagonists; 18% had a complete response, and 46% had a partial response. However, 33 (25%) patients showed no change, and 14 (11%) had continued disease progression despite treatment with TNF antagonists. In another 16 patients who received a second TNF antagonist, 10 (63%) had a complete or partial clinical response. The investigators could find no differences in response between anti-TNF agents or between monotherapy and a combination with an immunosuppressant.

Pulmonary involvement was associated with a significantly lower clinical response, but none of the other factors examined in a multivariate analysis (sex, age, ethnicity, organ involvement, disease duration, steroid dosage, or prior immunosuppressant use) distinguished responders and nonresponders.

The authors noted that these response rates were lower than those seen in the literature and suggested this may be attributable to the multicenter design, more patients with longer-lasting and more refractory disease, and longer times under biologic therapy (median 12 months).

The researchers reported significant improvements in central nervous system, peripheral nervous system, heart, skin, and upper respiratory tract involvements based on declines in Extrapulmonary Physician Organ Severity Tool (ePOST) scores. There were also improvements in the eye, muscle, and lung, but these were not statistically significant.

TNF-antagonist therapy was associated with a high rate of adverse events. Around half of all patients (52%) experienced adverse events, such as pneumonia, urinary tract infections, bacterial sepsis, and herpes zoster. In 31 patients (23%), these led to treatment cessation.

Nine patients also had severe allergic reactions, four had paradoxical granulomatous reactions, three developed neutralizing antibodies against anti-TNF agents, two patients had demyelinating lesions, and one had a serum sickness-like reaction. All of these events led to discontinuation.

Overall, 128 (97%) of the patients in the study had received corticosteroids as first-line therapy, and 125 (95%) had received at least one second-line immunosuppressive drug over a median duration of 16 months. Most were treated with infliximab (91%) as the first-line TNF antagonist, followed by adalimumab (6%), etanercept (2%), and certolizumab pegol (1%).

Treatment with TNF antagonists was associated with significant reductions in corticosteroid use; the mean daily prednisone dose decreased from 23 mg/day to 11 mg/day over the median 20.5-month follow-up. This was seen even in the 33 patients who showed no change in their disease course after TNF-antagonist therapy.

No conflicts of interest were declared.

rhnews@frontlinemedcom.com

Global cases of HIV from 2015 to 2035 would be reduced by over 50% if the Joint United Nations Program on HIV/AIDS 95/95/95 target is met and a moderately effective HIV vaccine is introduced by 2020, according to new research published in Proceedings of the National Academy of Sciences.

A custom model based on current rates of diagnosis and treatment in 127 countries predicts that a total of 49 million new cases of HIV would occur globally from 2015 to 2035, investigators said. Achieving the UNAIDS goal of 95% disease diagnosis, 95% antiretroviral coverage, and 95% viral suppression by 2030 would avert 25 million cases by 2035. Achieving the more modest 90/90/90 target would avert 22 million cases within the same time period.

grandeduc/Thinkstock

lfranki@frontlinemedcom.com

On Twitter @IDPractitioner

Global cases of HIV from 2015 to 2035 would be reduced by over 50% if the Joint United Nations Program on HIV/AIDS 95/95/95 target is met and a moderately effective HIV vaccine is introduced by 2020, according to new research published in Proceedings of the National Academy of Sciences.

A custom model based on current rates of diagnosis and treatment in 127 countries predicts that a total of 49 million new cases of HIV would occur globally from 2015 to 2035, investigators said. Achieving the UNAIDS goal of 95% disease diagnosis, 95% antiretroviral coverage, and 95% viral suppression by 2030 would avert 25 million cases by 2035. Achieving the more modest 90/90/90 target would avert 22 million cases within the same time period.

grandeduc/Thinkstock

lfranki@frontlinemedcom.com

On Twitter @IDPractitioner

Global cases of HIV from 2015 to 2035 would be reduced by over 50% if the Joint United Nations Program on HIV/AIDS 95/95/95 target is met and a moderately effective HIV vaccine is introduced by 2020, according to new research published in Proceedings of the National Academy of Sciences.

A custom model based on current rates of diagnosis and treatment in 127 countries predicts that a total of 49 million new cases of HIV would occur globally from 2015 to 2035, investigators said. Achieving the UNAIDS goal of 95% disease diagnosis, 95% antiretroviral coverage, and 95% viral suppression by 2030 would avert 25 million cases by 2035. Achieving the more modest 90/90/90 target would avert 22 million cases within the same time period.

grandeduc/Thinkstock

lfranki@frontlinemedcom.com

On Twitter @IDPractitioner

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

ORLANDO – A large proportion of patients with advanced non–small cell lung cancer (NSCLC) are not being tested for tumor associated–epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) alterations according to national guidelines. This situation may be leading to suboptimal treatment, a large retrospective cohort study suggests.

Guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend testing before first-line therapy for all treatment-eligible patients with nonsquamous histology and for those patients with squamous histology who are nonsmokers or who have mixed cell types or small tumor samples. Additionally, the guidelines recommend that results be made available within 2 weeks of the lab’s receipt of the sample so that they can be used to inform treatment decisions.

Study details

For the study, the investigators identified 16,316 patients with advanced NSCLC from 206 community clinics across the United States participating in the Flatiron Network. All patients were treated between 2014 and 2016.

Cross-checking of the total Flatiron population against the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results databases suggested that it is a good national representation, according to Mr. Rughani.

A record review showed that the rate of EGFR and ALK testing among study patients ranged widely across clinics, from 0% to 100% for both the nonsquamous cases and the squamous cases, according to results reported in a poster session. The median was 79% for the former and 16% for the latter.

Overall, 22% of the nonsquamous cohort and 79% of the squamous cohort did not have any evidence of testing in their records. For the latter, a sampling of records was unable to verify whether testing was appropriately matched to eligibility criteria.

When testing was performed, 35% of EGFR test results and 37% of ALK test results were not available to the treating clinician until more than 4 weeks after the date of the advanced cancer diagnosis.

“The delays were mostly attributed to nonlab factors. When we isolated the time that the lab took to turn it around, it was under 2 weeks for the vast majority of patients,” Mr. Rughani reported. Possible nonlab culprit factors include clinic work flows, insurance-related issues, and families’ and patients’ hesitancy to be tested, he said.

Delays in receipt of positive test results appeared to influence choice of first-line therapy. Among patients in whom these results were available before first-line therapy, 80% of those found to have an EGFR-mutated tumor received an EGFR–tyrosine kinase inhibitor, and 77% of those found to have ALK-rearranged tumors received an ALK inhibitor.

In sharp contrast, among patients in whom positive test results did not become available until after the start of first-line therapy, respective values were just 43% and 42%.

“Anecdotally, we saw that some patients would go on to Avastin [bevacizumab] in the front line when the results were delayed, and then, ultimately, they would have the opportunity to receive an EGFR[–tyrosine kinase inhibitor] or something like that in later lines,” commented Mr. Rughani. “So, that impacted treatment decisions there.”

Mr. Rughani disclosed stock and other ownership interests in Flatiron Health.

op@frontlinemedcom.com

ORLANDO – A large proportion of patients with advanced non–small cell lung cancer (NSCLC) are not being tested for tumor associated–epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) alterations according to national guidelines. This situation may be leading to suboptimal treatment, a large retrospective cohort study suggests.

Guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend testing before first-line therapy for all treatment-eligible patients with nonsquamous histology and for those patients with squamous histology who are nonsmokers or who have mixed cell types or small tumor samples. Additionally, the guidelines recommend that results be made available within 2 weeks of the lab’s receipt of the sample so that they can be used to inform treatment decisions.

Study details

For the study, the investigators identified 16,316 patients with advanced NSCLC from 206 community clinics across the United States participating in the Flatiron Network. All patients were treated between 2014 and 2016.

Cross-checking of the total Flatiron population against the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results databases suggested that it is a good national representation, according to Mr. Rughani.

A record review showed that the rate of EGFR and ALK testing among study patients ranged widely across clinics, from 0% to 100% for both the nonsquamous cases and the squamous cases, according to results reported in a poster session. The median was 79% for the former and 16% for the latter.

Overall, 22% of the nonsquamous cohort and 79% of the squamous cohort did not have any evidence of testing in their records. For the latter, a sampling of records was unable to verify whether testing was appropriately matched to eligibility criteria.

When testing was performed, 35% of EGFR test results and 37% of ALK test results were not available to the treating clinician until more than 4 weeks after the date of the advanced cancer diagnosis.

“The delays were mostly attributed to nonlab factors. When we isolated the time that the lab took to turn it around, it was under 2 weeks for the vast majority of patients,” Mr. Rughani reported. Possible nonlab culprit factors include clinic work flows, insurance-related issues, and families’ and patients’ hesitancy to be tested, he said.

Delays in receipt of positive test results appeared to influence choice of first-line therapy. Among patients in whom these results were available before first-line therapy, 80% of those found to have an EGFR-mutated tumor received an EGFR–tyrosine kinase inhibitor, and 77% of those found to have ALK-rearranged tumors received an ALK inhibitor.

In sharp contrast, among patients in whom positive test results did not become available until after the start of first-line therapy, respective values were just 43% and 42%.

“Anecdotally, we saw that some patients would go on to Avastin [bevacizumab] in the front line when the results were delayed, and then, ultimately, they would have the opportunity to receive an EGFR[–tyrosine kinase inhibitor] or something like that in later lines,” commented Mr. Rughani. “So, that impacted treatment decisions there.”

Mr. Rughani disclosed stock and other ownership interests in Flatiron Health.

op@frontlinemedcom.com

ORLANDO – A large proportion of patients with advanced non–small cell lung cancer (NSCLC) are not being tested for tumor associated–epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) alterations according to national guidelines. This situation may be leading to suboptimal treatment, a large retrospective cohort study suggests.

Guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend testing before first-line therapy for all treatment-eligible patients with nonsquamous histology and for those patients with squamous histology who are nonsmokers or who have mixed cell types or small tumor samples. Additionally, the guidelines recommend that results be made available within 2 weeks of the lab’s receipt of the sample so that they can be used to inform treatment decisions.

Study details

For the study, the investigators identified 16,316 patients with advanced NSCLC from 206 community clinics across the United States participating in the Flatiron Network. All patients were treated between 2014 and 2016.

Cross-checking of the total Flatiron population against the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results databases suggested that it is a good national representation, according to Mr. Rughani.

A record review showed that the rate of EGFR and ALK testing among study patients ranged widely across clinics, from 0% to 100% for both the nonsquamous cases and the squamous cases, according to results reported in a poster session. The median was 79% for the former and 16% for the latter.

Overall, 22% of the nonsquamous cohort and 79% of the squamous cohort did not have any evidence of testing in their records. For the latter, a sampling of records was unable to verify whether testing was appropriately matched to eligibility criteria.

When testing was performed, 35% of EGFR test results and 37% of ALK test results were not available to the treating clinician until more than 4 weeks after the date of the advanced cancer diagnosis.

“The delays were mostly attributed to nonlab factors. When we isolated the time that the lab took to turn it around, it was under 2 weeks for the vast majority of patients,” Mr. Rughani reported. Possible nonlab culprit factors include clinic work flows, insurance-related issues, and families’ and patients’ hesitancy to be tested, he said.

Delays in receipt of positive test results appeared to influence choice of first-line therapy. Among patients in whom these results were available before first-line therapy, 80% of those found to have an EGFR-mutated tumor received an EGFR–tyrosine kinase inhibitor, and 77% of those found to have ALK-rearranged tumors received an ALK inhibitor.

In sharp contrast, among patients in whom positive test results did not become available until after the start of first-line therapy, respective values were just 43% and 42%.

“Anecdotally, we saw that some patients would go on to Avastin [bevacizumab] in the front line when the results were delayed, and then, ultimately, they would have the opportunity to receive an EGFR[–tyrosine kinase inhibitor] or something like that in later lines,” commented Mr. Rughani. “So, that impacted treatment decisions there.”

Mr. Rughani disclosed stock and other ownership interests in Flatiron Health.

op@frontlinemedcom.com

The decline in U.S. influenza activity that started in February paused during the week ending March 11, according to the U.S. Centers for Disease Control and Prevention.

The proportion of outpatient visits for influenza-like illness (ILI) stayed at 3.7% for a second consecutive week after declining for 3 weeks in a row. The peak for the season, 5.2%, came during the week ending Feb. 11, CDC data show. The national baseline is 2.2%.

rfranki@frontlinemedcom.com

The decline in U.S. influenza activity that started in February paused during the week ending March 11, according to the U.S. Centers for Disease Control and Prevention.

The proportion of outpatient visits for influenza-like illness (ILI) stayed at 3.7% for a second consecutive week after declining for 3 weeks in a row. The peak for the season, 5.2%, came during the week ending Feb. 11, CDC data show. The national baseline is 2.2%.

rfranki@frontlinemedcom.com

The decline in U.S. influenza activity that started in February paused during the week ending March 11, according to the U.S. Centers for Disease Control and Prevention.

The proportion of outpatient visits for influenza-like illness (ILI) stayed at 3.7% for a second consecutive week after declining for 3 weeks in a row. The peak for the season, 5.2%, came during the week ending Feb. 11, CDC data show. The national baseline is 2.2%.

rfranki@frontlinemedcom.com

At one time, respiratory failure was the primary cause of death in young men and boys with muscular dystrophies, but since improvements in ventilator support have addressed this problem, cardiac complications such as cardiomyopathy have become the main cause of death in this group, with the highest risk of death in people with Duchenne muscular dystrophy (DMD). Researchers from Rome have reported that the novel use of ventricular assist devices in this population can prolong life.

Gianluigi Perri, MD, PhD, of University Hospital and Bambino Gesù Children Hospital in Rome, and his coauthors, shared their experience treating seven patients with dystrophinopathies and dilated cardiomyopathy (DCM) with left ventricular assist devices (LVADs) from February 2011 to February 2016 (J Thorac Cardiovasc Surg. 2017 March;153:669-74). “Our experience indicates that the use of an LVAD as destination therapy in patients with dystrophinopathies with end-stage DCM is feasible, suggesting that it may be suitable as a palliative therapy for the treatment of these patients with no other therapeutic options,” Dr. Perri and his coauthors said.

Heart transplantation is considered the procedure of choice for children with severe advanced heart failure, but transplantation is contraindicated for children with dystrophinopathies because of the risk of respiratory failure and progression of skeletal myopathy leads to limited functional capacity. Hence, Dr. Perri and his coauthors developed their alternative treatment for end-stage heart failure in these children. They used the Jarvik 2000 LVAD (Jarvik Heart Inc., New York) as destination therapy.

Six of the seven patients they operated on had DMD and one had beta-2 sarcoglycan deficit. Their ages ranged from 14.2 to 23.4 years. Two patients had early complications: retropharyngeal bleeding and cholecystectomy; and abdominal bleeding and splenectomy. Two different patients had late complications: gastrostomy; and osteolysis and infection at the pedestal site. Three patients died after the operation: one of stroke at 15 months; one of severe bleeding about 28 months later; and one of lung infection 45 months afterward. Follow-up for the surviving patients ranged from about 2 months to 40 months. Median hospital stay was 77 days.

Dr. Perri and his coauthors noted that the DMD Care Considerations Working Group expanded acceptable therapies for DMD cardiomyopathy to include novel treatments such as mechanical circulatory support and implantable cardioverter-defibrillators.

“Although the best approach remains unclear, it does seem clear that treatment should be more aggressive,” the researchers said. The limited life expectancy of these patients makes transplantation a complicated choice when a shortage of donors is a concern. “Therefore, the alternative therapeutic option is the use of LVAD,” Dr. Perri and his coauthors said.

These patients need care at centers “with a high level of experience of patients with DMD,” the researchers stated. Common comorbidities such as severe kyphoscoliosis and respiratory muscle weakness in this population increase surgical risks.

Dr. Perri and his coauthors used a surgical technique that involved avoiding the left thoracotomy approach common in adults who undergo VAD implantation, because of respiratory insufficiency in these younger patients. They also used cardiopulmonary bypass in all but one patient who had a minimally invasive off-pump procedure through a left anterior minithoracotomy.

The researchers “strongly suggest” noninvasive ventilation after surgery to assist in pulmonary function often compromised by scoliosis and muscle weakness. “Our experience shows that postoperative care can be extremely challenging and is often burdened by unexpected complications,” they noted.

Kyphoscoliosis poses challenges when placing drains, and complications of these patients should be treated only in a specialized center. “Indeed, one of our patients died in a peripheral hospital because they underwent bronchoscopic examination with an endoscope that caused severe and intractable retropharyngeal bleeding,” they said.

The researchers no relevant financial relationships to disclose.

At one time, respiratory failure was the primary cause of death in young men and boys with muscular dystrophies, but since improvements in ventilator support have addressed this problem, cardiac complications such as cardiomyopathy have become the main cause of death in this group, with the highest risk of death in people with Duchenne muscular dystrophy (DMD). Researchers from Rome have reported that the novel use of ventricular assist devices in this population can prolong life.

Gianluigi Perri, MD, PhD, of University Hospital and Bambino Gesù Children Hospital in Rome, and his coauthors, shared their experience treating seven patients with dystrophinopathies and dilated cardiomyopathy (DCM) with left ventricular assist devices (LVADs) from February 2011 to February 2016 (J Thorac Cardiovasc Surg. 2017 March;153:669-74). “Our experience indicates that the use of an LVAD as destination therapy in patients with dystrophinopathies with end-stage DCM is feasible, suggesting that it may be suitable as a palliative therapy for the treatment of these patients with no other therapeutic options,” Dr. Perri and his coauthors said.

Heart transplantation is considered the procedure of choice for children with severe advanced heart failure, but transplantation is contraindicated for children with dystrophinopathies because of the risk of respiratory failure and progression of skeletal myopathy leads to limited functional capacity. Hence, Dr. Perri and his coauthors developed their alternative treatment for end-stage heart failure in these children. They used the Jarvik 2000 LVAD (Jarvik Heart Inc., New York) as destination therapy.

Six of the seven patients they operated on had DMD and one had beta-2 sarcoglycan deficit. Their ages ranged from 14.2 to 23.4 years. Two patients had early complications: retropharyngeal bleeding and cholecystectomy; and abdominal bleeding and splenectomy. Two different patients had late complications: gastrostomy; and osteolysis and infection at the pedestal site. Three patients died after the operation: one of stroke at 15 months; one of severe bleeding about 28 months later; and one of lung infection 45 months afterward. Follow-up for the surviving patients ranged from about 2 months to 40 months. Median hospital stay was 77 days.

Dr. Perri and his coauthors noted that the DMD Care Considerations Working Group expanded acceptable therapies for DMD cardiomyopathy to include novel treatments such as mechanical circulatory support and implantable cardioverter-defibrillators.

“Although the best approach remains unclear, it does seem clear that treatment should be more aggressive,” the researchers said. The limited life expectancy of these patients makes transplantation a complicated choice when a shortage of donors is a concern. “Therefore, the alternative therapeutic option is the use of LVAD,” Dr. Perri and his coauthors said.

These patients need care at centers “with a high level of experience of patients with DMD,” the researchers stated. Common comorbidities such as severe kyphoscoliosis and respiratory muscle weakness in this population increase surgical risks.

Dr. Perri and his coauthors used a surgical technique that involved avoiding the left thoracotomy approach common in adults who undergo VAD implantation, because of respiratory insufficiency in these younger patients. They also used cardiopulmonary bypass in all but one patient who had a minimally invasive off-pump procedure through a left anterior minithoracotomy.

The researchers “strongly suggest” noninvasive ventilation after surgery to assist in pulmonary function often compromised by scoliosis and muscle weakness. “Our experience shows that postoperative care can be extremely challenging and is often burdened by unexpected complications,” they noted.

Kyphoscoliosis poses challenges when placing drains, and complications of these patients should be treated only in a specialized center. “Indeed, one of our patients died in a peripheral hospital because they underwent bronchoscopic examination with an endoscope that caused severe and intractable retropharyngeal bleeding,” they said.

The researchers no relevant financial relationships to disclose.

At one time, respiratory failure was the primary cause of death in young men and boys with muscular dystrophies, but since improvements in ventilator support have addressed this problem, cardiac complications such as cardiomyopathy have become the main cause of death in this group, with the highest risk of death in people with Duchenne muscular dystrophy (DMD). Researchers from Rome have reported that the novel use of ventricular assist devices in this population can prolong life.

Gianluigi Perri, MD, PhD, of University Hospital and Bambino Gesù Children Hospital in Rome, and his coauthors, shared their experience treating seven patients with dystrophinopathies and dilated cardiomyopathy (DCM) with left ventricular assist devices (LVADs) from February 2011 to February 2016 (J Thorac Cardiovasc Surg. 2017 March;153:669-74). “Our experience indicates that the use of an LVAD as destination therapy in patients with dystrophinopathies with end-stage DCM is feasible, suggesting that it may be suitable as a palliative therapy for the treatment of these patients with no other therapeutic options,” Dr. Perri and his coauthors said.

Heart transplantation is considered the procedure of choice for children with severe advanced heart failure, but transplantation is contraindicated for children with dystrophinopathies because of the risk of respiratory failure and progression of skeletal myopathy leads to limited functional capacity. Hence, Dr. Perri and his coauthors developed their alternative treatment for end-stage heart failure in these children. They used the Jarvik 2000 LVAD (Jarvik Heart Inc., New York) as destination therapy.

Six of the seven patients they operated on had DMD and one had beta-2 sarcoglycan deficit. Their ages ranged from 14.2 to 23.4 years. Two patients had early complications: retropharyngeal bleeding and cholecystectomy; and abdominal bleeding and splenectomy. Two different patients had late complications: gastrostomy; and osteolysis and infection at the pedestal site. Three patients died after the operation: one of stroke at 15 months; one of severe bleeding about 28 months later; and one of lung infection 45 months afterward. Follow-up for the surviving patients ranged from about 2 months to 40 months. Median hospital stay was 77 days.

Dr. Perri and his coauthors noted that the DMD Care Considerations Working Group expanded acceptable therapies for DMD cardiomyopathy to include novel treatments such as mechanical circulatory support and implantable cardioverter-defibrillators.

“Although the best approach remains unclear, it does seem clear that treatment should be more aggressive,” the researchers said. The limited life expectancy of these patients makes transplantation a complicated choice when a shortage of donors is a concern. “Therefore, the alternative therapeutic option is the use of LVAD,” Dr. Perri and his coauthors said.

These patients need care at centers “with a high level of experience of patients with DMD,” the researchers stated. Common comorbidities such as severe kyphoscoliosis and respiratory muscle weakness in this population increase surgical risks.

Dr. Perri and his coauthors used a surgical technique that involved avoiding the left thoracotomy approach common in adults who undergo VAD implantation, because of respiratory insufficiency in these younger patients. They also used cardiopulmonary bypass in all but one patient who had a minimally invasive off-pump procedure through a left anterior minithoracotomy.

The researchers “strongly suggest” noninvasive ventilation after surgery to assist in pulmonary function often compromised by scoliosis and muscle weakness. “Our experience shows that postoperative care can be extremely challenging and is often burdened by unexpected complications,” they noted.

Kyphoscoliosis poses challenges when placing drains, and complications of these patients should be treated only in a specialized center. “Indeed, one of our patients died in a peripheral hospital because they underwent bronchoscopic examination with an endoscope that caused severe and intractable retropharyngeal bleeding,” they said.

The researchers no relevant financial relationships to disclose.

ORLANDO – Ignorance and exposure are teaming up to put Latinos in the bull’s-eye of skin cancer.

Many believe that they are not at risk for either melanoma or nonmelanoma skin cancers – and too often, their physicians believe the same, Maritza Perez, MD, said at the annual meeting of the American Academy of Dermatology. Because of such incorrect perceptions, Latino patients get little counseling about risky behaviors, and so their exposure to those dangers continues unabated.

“The behavior of many Hispanic patients is very risky,” said Dr. Perez, a clinical professor of dermatology, at Mount Sinai Medical Center, New York. “They don’t wear sunscreen. They don’t do skin self-exams. They use tanning beds. And because of these beliefs, they don’t educate their children about sun safety.”

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

ORLANDO – Ignorance and exposure are teaming up to put Latinos in the bull’s-eye of skin cancer.

Many believe that they are not at risk for either melanoma or nonmelanoma skin cancers – and too often, their physicians believe the same, Maritza Perez, MD, said at the annual meeting of the American Academy of Dermatology. Because of such incorrect perceptions, Latino patients get little counseling about risky behaviors, and so their exposure to those dangers continues unabated.

“The behavior of many Hispanic patients is very risky,” said Dr. Perez, a clinical professor of dermatology, at Mount Sinai Medical Center, New York. “They don’t wear sunscreen. They don’t do skin self-exams. They use tanning beds. And because of these beliefs, they don’t educate their children about sun safety.”

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

ORLANDO – Ignorance and exposure are teaming up to put Latinos in the bull’s-eye of skin cancer.

Many believe that they are not at risk for either melanoma or nonmelanoma skin cancers – and too often, their physicians believe the same, Maritza Perez, MD, said at the annual meeting of the American Academy of Dermatology. Because of such incorrect perceptions, Latino patients get little counseling about risky behaviors, and so their exposure to those dangers continues unabated.

“The behavior of many Hispanic patients is very risky,” said Dr. Perez, a clinical professor of dermatology, at Mount Sinai Medical Center, New York. “They don’t wear sunscreen. They don’t do skin self-exams. They use tanning beds. And because of these beliefs, they don’t educate their children about sun safety.”

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

WAILEA, HAWAII – Oral apremilast is a drug in search of a compelling indication, Craig L. Leonardi, MD, declared at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.

“Apremilast is the least effective systemic agent for the treatment of psoriasis. That’s a statement of fact. I think the drug is mismatched for the treatment of moderate to severe plaque psoriasis. In fact, many of us gave the company that advice early on, but it was a program that was set in stone at that point,” according to Dr. Leonardi, a dermatologist at Saint Louis University and a prominent psoriasis clinical trialist.

Bruce Jancin/Frontline Medical News

What efficacy can be anticipated?

In the pivotal phase III ESTEEM I trial conducted in 844 patients with moderate to severe psoriasis (J Am Acad Dermatol. 2015 Jul;73[1]:37-49), the overall PASI-75 response rate at week 16 in patients assigned to apremilast at 30 mg twice daily was 33%, significantly better than the 5% placebo response rate, but substantially less than what’s achieved with the tumor necrosis factor inhibitors and other injectable biologic agents.

Moreover, in the pivotal phase III PALACE 1 study of apremilast for the treatment of psoriatic arthritis, the primary outcome of at least a 20% improvement in the modified American College of Rheumatology response criteria at week 16 was achieved in 40% of patients randomized to apremilast at 30 mg twice daily, compared with 19% on placebo (Ann Rheum Dis. 2014 Jun;73[6]:1020-6). Again, that doesn’t approach the efficacy of a TNF inhibitor, Dr. Leonardi noted.

On the plus side, an oral agent such as apremilast is an attractive option for treatment-adherent patients. Plus, the drug has a favorable safety profile and is well tolerated, with mild to moderate side effects that appear early and are self-limited. In ESTEEM I, for example, more than 96% of patients had either no or only mild to moderate adverse events. The incidence of the two most common adverse events, diarrhea and nausea, at 19% and 16%, respectively, was more than double that in placebo-treated controls, but rates of other adverse events were similar in the two treatment arms.

Symposium codirector Linda Stein Gold, MD, director of dermatology research at the Henry Ford Health System in Detroit, said a clinical trial of apremilast conducted specifically in patients with moderate psoriasis has recently been completed. When those results become available they should shore up the drug’s use in that population.
 

Finding potential in off-label use

“This drug may have been brought to market for psoriasis, but I think its utility is so much more in other diseases where inflammation is an important mechanism,” said Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research in San Diego. “Most of my use of apremilast is off-label for atopic dermatitis, for lichen planus, and I’ve tried it in a lot of patients where it has worked for discoid lupus. There’s so much potential for apremilast,” said Dr. Bhatia.

Dr. Leonardi remained unpersuaded.

“Your glass of water is half full, mine is half empty in this case,” he replied. “This drug has been approved now for at least 3 years, and we are still looking at the occasional favorable case report that flies up. I’ve got to say this drug is having a hard time finding a place outside of psoriasis, but we’ll all see.”

Dr. Leonardi reported having financial relationships with more than a dozen pharmaceutical companies, including Celgene, which markets apremilast. Dr. Stein Gold, too, has received research grants from and serves as a consultant to numerous drug companies, including Celgene. Dr. Bhatia declared having financial relationships with more than two dozen.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAILEA, HAWAII – Oral apremilast is a drug in search of a compelling indication, Craig L. Leonardi, MD, declared at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.

“Apremilast is the least effective systemic agent for the treatment of psoriasis. That’s a statement of fact. I think the drug is mismatched for the treatment of moderate to severe plaque psoriasis. In fact, many of us gave the company that advice early on, but it was a program that was set in stone at that point,” according to Dr. Leonardi, a dermatologist at Saint Louis University and a prominent psoriasis clinical trialist.

Bruce Jancin/Frontline Medical News

What efficacy can be anticipated?

In the pivotal phase III ESTEEM I trial conducted in 844 patients with moderate to severe psoriasis (J Am Acad Dermatol. 2015 Jul;73[1]:37-49), the overall PASI-75 response rate at week 16 in patients assigned to apremilast at 30 mg twice daily was 33%, significantly better than the 5% placebo response rate, but substantially less than what’s achieved with the tumor necrosis factor inhibitors and other injectable biologic agents.

Moreover, in the pivotal phase III PALACE 1 study of apremilast for the treatment of psoriatic arthritis, the primary outcome of at least a 20% improvement in the modified American College of Rheumatology response criteria at week 16 was achieved in 40% of patients randomized to apremilast at 30 mg twice daily, compared with 19% on placebo (Ann Rheum Dis. 2014 Jun;73[6]:1020-6). Again, that doesn’t approach the efficacy of a TNF inhibitor, Dr. Leonardi noted.

On the plus side, an oral agent such as apremilast is an attractive option for treatment-adherent patients. Plus, the drug has a favorable safety profile and is well tolerated, with mild to moderate side effects that appear early and are self-limited. In ESTEEM I, for example, more than 96% of patients had either no or only mild to moderate adverse events. The incidence of the two most common adverse events, diarrhea and nausea, at 19% and 16%, respectively, was more than double that in placebo-treated controls, but rates of other adverse events were similar in the two treatment arms.

Symposium codirector Linda Stein Gold, MD, director of dermatology research at the Henry Ford Health System in Detroit, said a clinical trial of apremilast conducted specifically in patients with moderate psoriasis has recently been completed. When those results become available they should shore up the drug’s use in that population.
 

Finding potential in off-label use

“This drug may have been brought to market for psoriasis, but I think its utility is so much more in other diseases where inflammation is an important mechanism,” said Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research in San Diego. “Most of my use of apremilast is off-label for atopic dermatitis, for lichen planus, and I’ve tried it in a lot of patients where it has worked for discoid lupus. There’s so much potential for apremilast,” said Dr. Bhatia.

Dr. Leonardi remained unpersuaded.

“Your glass of water is half full, mine is half empty in this case,” he replied. “This drug has been approved now for at least 3 years, and we are still looking at the occasional favorable case report that flies up. I’ve got to say this drug is having a hard time finding a place outside of psoriasis, but we’ll all see.”

Dr. Leonardi reported having financial relationships with more than a dozen pharmaceutical companies, including Celgene, which markets apremilast. Dr. Stein Gold, too, has received research grants from and serves as a consultant to numerous drug companies, including Celgene. Dr. Bhatia declared having financial relationships with more than two dozen.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com

WAILEA, HAWAII – Oral apremilast is a drug in search of a compelling indication, Craig L. Leonardi, MD, declared at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Research Foundation.

“Apremilast is the least effective systemic agent for the treatment of psoriasis. That’s a statement of fact. I think the drug is mismatched for the treatment of moderate to severe plaque psoriasis. In fact, many of us gave the company that advice early on, but it was a program that was set in stone at that point,” according to Dr. Leonardi, a dermatologist at Saint Louis University and a prominent psoriasis clinical trialist.

Bruce Jancin/Frontline Medical News

What efficacy can be anticipated?

In the pivotal phase III ESTEEM I trial conducted in 844 patients with moderate to severe psoriasis (J Am Acad Dermatol. 2015 Jul;73[1]:37-49), the overall PASI-75 response rate at week 16 in patients assigned to apremilast at 30 mg twice daily was 33%, significantly better than the 5% placebo response rate, but substantially less than what’s achieved with the tumor necrosis factor inhibitors and other injectable biologic agents.

Moreover, in the pivotal phase III PALACE 1 study of apremilast for the treatment of psoriatic arthritis, the primary outcome of at least a 20% improvement in the modified American College of Rheumatology response criteria at week 16 was achieved in 40% of patients randomized to apremilast at 30 mg twice daily, compared with 19% on placebo (Ann Rheum Dis. 2014 Jun;73[6]:1020-6). Again, that doesn’t approach the efficacy of a TNF inhibitor, Dr. Leonardi noted.

On the plus side, an oral agent such as apremilast is an attractive option for treatment-adherent patients. Plus, the drug has a favorable safety profile and is well tolerated, with mild to moderate side effects that appear early and are self-limited. In ESTEEM I, for example, more than 96% of patients had either no or only mild to moderate adverse events. The incidence of the two most common adverse events, diarrhea and nausea, at 19% and 16%, respectively, was more than double that in placebo-treated controls, but rates of other adverse events were similar in the two treatment arms.

Symposium codirector Linda Stein Gold, MD, director of dermatology research at the Henry Ford Health System in Detroit, said a clinical trial of apremilast conducted specifically in patients with moderate psoriasis has recently been completed. When those results become available they should shore up the drug’s use in that population.
 

Finding potential in off-label use

“This drug may have been brought to market for psoriasis, but I think its utility is so much more in other diseases where inflammation is an important mechanism,” said Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research in San Diego. “Most of my use of apremilast is off-label for atopic dermatitis, for lichen planus, and I’ve tried it in a lot of patients where it has worked for discoid lupus. There’s so much potential for apremilast,” said Dr. Bhatia.

Dr. Leonardi remained unpersuaded.

“Your glass of water is half full, mine is half empty in this case,” he replied. “This drug has been approved now for at least 3 years, and we are still looking at the occasional favorable case report that flies up. I’ve got to say this drug is having a hard time finding a place outside of psoriasis, but we’ll all see.”

Dr. Leonardi reported having financial relationships with more than a dozen pharmaceutical companies, including Celgene, which markets apremilast. Dr. Stein Gold, too, has received research grants from and serves as a consultant to numerous drug companies, including Celgene. Dr. Bhatia declared having financial relationships with more than two dozen.

SDEF and this news organization are owned by the same parent company.

bjancin@frontlinemedcom.com