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First Basal Cell Carcinoma Brings Risk for More
LISBON – Nearly 30% of patients diagnosed with a first pathologically confirmed basal cell carcinoma will develop one or more additional primary basal cell carcinomas within 5 years.
This finding, from a comprehensive Dutch national cancer registry, has important implications for clinical practice, noted Dr. Sophie C. Flohil at the annual congress of the European Academy of Dermatology and Venereology.
"Based upon our results, we would like to recommend that all BCC [basal cell carcinoma] patients undergo annual follow-up visits with full-body skin examinations for at least 3 years after their first BCC diagnosis."
She presented a cohort study involving 2,483 consecutive unselected Dutch patients diagnosed with a first histological confirmed BCC during 2004.
During 5 years of prospective follow-up in PALGA, the Dutch nationwide network and registry of histo- and cytopathology, 29.2% of the patients were diagnosed with one or more additional primary BCCs, according to Dr. Flohil, a dermatology resident at Erasmus University, Rotterdam, the Netherlands.
More than one-third of patients who developed a second primary BCC within 5 years did so during the first 6 months after diagnosis of the first.
The cumulative risk during the first 6 months of follow-up was extraordinarily high at 11.2%, as compared with 13.9% through 1 year, 18.5% after 2 years, 22.1% at 3 years, 25.5% after 4 years, and 29.2% after 5 years, she said. This translates into an incidence rate of 25,318 cases per 100,000 person-years during the first half-year after diagnosis of a first primary tumor.
"We think that this could indicate that these second BCCs that occur in the first 6 months after a first BCC diagnosis were already present at the date of the first BCC diagnosis, but were somehow missed then by the dermatologist or the doctor they went to," she said.
Still, the incidence rate remained quite high during the first several years of follow-up: 15,737 cases per 100,000 person-years through the first year and 10,779 per 100,000 person-years after 2 years before tailing off to 8,752 per 100,000 person-years at 3 years.
In a multivariate analysis, men had an adjusted 30% increased risk of developing one or more subsequent BCCs, and patients aged 65-79 years had an 81% greater risk than those under age 50.
Dr. Flohil declared having no financial conflicts of interest.
LISBON – Nearly 30% of patients diagnosed with a first pathologically confirmed basal cell carcinoma will develop one or more additional primary basal cell carcinomas within 5 years.
This finding, from a comprehensive Dutch national cancer registry, has important implications for clinical practice, noted Dr. Sophie C. Flohil at the annual congress of the European Academy of Dermatology and Venereology.
"Based upon our results, we would like to recommend that all BCC [basal cell carcinoma] patients undergo annual follow-up visits with full-body skin examinations for at least 3 years after their first BCC diagnosis."
She presented a cohort study involving 2,483 consecutive unselected Dutch patients diagnosed with a first histological confirmed BCC during 2004.
During 5 years of prospective follow-up in PALGA, the Dutch nationwide network and registry of histo- and cytopathology, 29.2% of the patients were diagnosed with one or more additional primary BCCs, according to Dr. Flohil, a dermatology resident at Erasmus University, Rotterdam, the Netherlands.
More than one-third of patients who developed a second primary BCC within 5 years did so during the first 6 months after diagnosis of the first.
The cumulative risk during the first 6 months of follow-up was extraordinarily high at 11.2%, as compared with 13.9% through 1 year, 18.5% after 2 years, 22.1% at 3 years, 25.5% after 4 years, and 29.2% after 5 years, she said. This translates into an incidence rate of 25,318 cases per 100,000 person-years during the first half-year after diagnosis of a first primary tumor.
"We think that this could indicate that these second BCCs that occur in the first 6 months after a first BCC diagnosis were already present at the date of the first BCC diagnosis, but were somehow missed then by the dermatologist or the doctor they went to," she said.
Still, the incidence rate remained quite high during the first several years of follow-up: 15,737 cases per 100,000 person-years through the first year and 10,779 per 100,000 person-years after 2 years before tailing off to 8,752 per 100,000 person-years at 3 years.
In a multivariate analysis, men had an adjusted 30% increased risk of developing one or more subsequent BCCs, and patients aged 65-79 years had an 81% greater risk than those under age 50.
Dr. Flohil declared having no financial conflicts of interest.
LISBON – Nearly 30% of patients diagnosed with a first pathologically confirmed basal cell carcinoma will develop one or more additional primary basal cell carcinomas within 5 years.
This finding, from a comprehensive Dutch national cancer registry, has important implications for clinical practice, noted Dr. Sophie C. Flohil at the annual congress of the European Academy of Dermatology and Venereology.
"Based upon our results, we would like to recommend that all BCC [basal cell carcinoma] patients undergo annual follow-up visits with full-body skin examinations for at least 3 years after their first BCC diagnosis."
She presented a cohort study involving 2,483 consecutive unselected Dutch patients diagnosed with a first histological confirmed BCC during 2004.
During 5 years of prospective follow-up in PALGA, the Dutch nationwide network and registry of histo- and cytopathology, 29.2% of the patients were diagnosed with one or more additional primary BCCs, according to Dr. Flohil, a dermatology resident at Erasmus University, Rotterdam, the Netherlands.
More than one-third of patients who developed a second primary BCC within 5 years did so during the first 6 months after diagnosis of the first.
The cumulative risk during the first 6 months of follow-up was extraordinarily high at 11.2%, as compared with 13.9% through 1 year, 18.5% after 2 years, 22.1% at 3 years, 25.5% after 4 years, and 29.2% after 5 years, she said. This translates into an incidence rate of 25,318 cases per 100,000 person-years during the first half-year after diagnosis of a first primary tumor.
"We think that this could indicate that these second BCCs that occur in the first 6 months after a first BCC diagnosis were already present at the date of the first BCC diagnosis, but were somehow missed then by the dermatologist or the doctor they went to," she said.
Still, the incidence rate remained quite high during the first several years of follow-up: 15,737 cases per 100,000 person-years through the first year and 10,779 per 100,000 person-years after 2 years before tailing off to 8,752 per 100,000 person-years at 3 years.
In a multivariate analysis, men had an adjusted 30% increased risk of developing one or more subsequent BCCs, and patients aged 65-79 years had an 81% greater risk than those under age 50.
Dr. Flohil declared having no financial conflicts of interest.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Major Finding: More than 29% of 2,483 consecutive patients diagnosed with a first histological confirmed basal cell carcinoma developed a second one within 5 years.
Data Source: A Dutch national cancer registry.
Disclosures: No financial conflicts.
New Psoriasis Biologics Achieve Promising Phase II Results
LISBON – Validation of the interleukin-17 cytokine family in psoriasis pathophysiology has gotten a boost from positive, phase II clinical trials involving two novel biologic agents.
The double-blind, placebo-controlled, phase II studies documented rapid and marked improvement in patients who had moderate to severe plaque psoriasis and were treated with secukinumab or AMG 827.
Roughly 80% of patients who were randomized to the maximum dose of either biologic experienced at least a PASI 75 (that is, improvement of 75% as measured by the Psoriasis Area and Severity Index) at 12 weeks. Those are efficacy rates in excess of the improvement obtainable with the earlier-generation biologics that targeted tumor necrosis factor–alpha, according to Dr. Kim A. Papp, who presented the data on both drugs at the annual congress of the European Academy of Dermatology and Venereology.
"This is a very robust, profound response suggesting that we’re really getting to the fundamentals of what’s driving psoriasis," Dr. Papp said.
Secukinumab is the agent further along in the developmental pipeline. A phase III clinical trial is already underway on the strength of three phase II studies presented at the congress.
Secukinumab is a fully human monoclonal antibody targeting IL-17A, a key member of the IL-17 cytokine family. The sequence of pathophysiologic events in psoriasis, as understood today, is that IL-23 induces activated Th17 cells, which in lesional skin express IL-17, in turn eliciting the production of proinflammatory cytokines by keratinocytes and keratinocyte hyperproliferation. IL-17A is one of several types of IL-17 that bind to the IL-17 receptor.
In contrast, AMG 827 is a human monoclonal antibody that blocks the IL-17 receptor itself, explained Dr. Papp, director of research at Probity Medical Research Inc. in Waterloo, Ont.
Secukinumab: Study 1
Dr. Papp presented the results of two of the three phase II studies of secukinumab. One study randomized 125 patients to subcutaneous secukinumab of 150 mg, 75 mg, or 25 mg once monthly for 3 months; to a single 25-mg dose; or to placebo.
The primary end point (PASI 75 response rate at 12 weeks) was 81%, 57%, 19%, 3%, and 9%, respectively. PASI 90 (that is, an improvement of 90% on the PASI) response rates were 52%, 19%, 8%, 0%, and 5%, respectively. Investigator Global Assessment scores of clear or almost clear at 12 weeks were achieved in 48% of patients in the 150-mg group and in 33% of those who received 75 mg, which were significantly better ratings than the 0%-12% rates in the other study arms.
Secukinumab: Study 2
The second secukinumab phase II study that was presented by Dr. Papp examined possible intravenous induction doses. The 100 participants were randomized to 3 mg/kg given on day 1; to 10 mg/kg on day 1; to 10 mg/kg on days 1, 15, and 29; or to placebo. The PASI 75 rates at 12 weeks were 40%, 75%, 83%, and 10%, respectively. The PASI 90 response rates were 10%, 54%, 76%, and 0%.
Secukinumab: Study 3
Dr. Phoebe A. Rich presented the third secukinumab phase II trial, which aimed to find the best dosing regimen. The study included 404 patients at 63 centers in seven countries who were randomized 1:2:2:1 to subcutaneous placebo; to a single 150-mg dose at week 0; to 150 mg at weeks 0, 4, and 8; or to 150 mg at weeks 0, 1, 2, and 4.
The treatment arm with dosing at weeks 0, 1, 2 and 4 was the winner, with a PASI 75 response rate of 55% at week 12, compared with 42% with dosing at weeks 0, 4, and 8; 11% for a single dose; and 2% with placebo. The corresponding PASI 90 rates were 32%, 17%, 3%, and 2%, added Dr. Phoebe of the Oregon Dermatology and Research Center, Portland.
None of these relatively brief trials suggested any safety signals. The side effect pattern was basically the same as in the placebo arms, according to the investigators.
AMG 827
Dr. Papp also presented the first phase II, randomized, double-blind trial of AMG 827. It involved 198 patients who were randomized to subcutaneous AMG 827 at 280 mg monthly; to 70, 140, or 210 mg every 2 weeks; or to placebo. The primary end point was the PASI 75 response rate at week 12. It was highest (83%) in patients who received 210 mg every 2 weeks.
Interestingly, nearly all of the PASI 75 responders were also PASI 90 responders. The PASI 90 and PASI 100 response rates in the group taking 210 mg every 2 weeks were 75% and 63%, respectively. Again, as for secukinumab, the safety profile was unremarkable.
The response waned 4-10 weeks after the last dose of AMG 827. This took the form of a gradual, progressive relapse rather than an abrupt rebound, noted Dr. Papp.
Dr. Papp said that the large turnout to his presentation at the meeting, "shows the interest and excitement that surrounds what I think is a new adventure and really a new revolution in the understanding and treatment of psoriasis."
Dr. Papp is on the advisory boards of Novartis, which is developing secukinumab, and Amgen, manufacturer of AMG 827. He is also an advisor to many other pharmaceutical companies developing drugs for psoriasis. Dr. Rich is also on the advisory board of Novartis and other companies that are developing drugs for psoriasis.
Although the phase II data are certainly encouraging, it is far too early to speculate as to the future of the two new anti-IL-17 biologics. That must await the outcome of the far larger and longer-term phase III studies, Dr. Kristian Reich said in an interview.
In particular, the issue of major adverse cardiovascular events is a potential concern with all agents that target IL-17, given the earlier experience with briakinumab. Development of the fully human monoclonal antibody that was directed against IL-12/23 was abandoned because of cardiovascular issues in the midst of phase III development, added Dr. Reich.
"Those of us who are developing new drugs for our armamentarium find we are in a perfect situation, with at least three interesting antibodies being developed: secukinumab, AMG 827, and the IL-23p19 antibody. Together, with ustekinumab, we now have a group of four antibodies, all of which influence the IL-23/Th17 pathway. It will be very interesting to see how good they are in taking care of psoriasis patients," he said.
Dr. Reich is the medical director of the Dermatologikum Hamburg. He has been involved in studies of all four agents and is on the advisory boards of numerous pharmaceutical companies with an interest in psoriasis therapies.
Although the phase II data are certainly encouraging, it is far too early to speculate as to the future of the two new anti-IL-17 biologics. That must await the outcome of the far larger and longer-term phase III studies, Dr. Kristian Reich said in an interview.
In particular, the issue of major adverse cardiovascular events is a potential concern with all agents that target IL-17, given the earlier experience with briakinumab. Development of the fully human monoclonal antibody that was directed against IL-12/23 was abandoned because of cardiovascular issues in the midst of phase III development, added Dr. Reich.
"Those of us who are developing new drugs for our armamentarium find we are in a perfect situation, with at least three interesting antibodies being developed: secukinumab, AMG 827, and the IL-23p19 antibody. Together, with ustekinumab, we now have a group of four antibodies, all of which influence the IL-23/Th17 pathway. It will be very interesting to see how good they are in taking care of psoriasis patients," he said.
Dr. Reich is the medical director of the Dermatologikum Hamburg. He has been involved in studies of all four agents and is on the advisory boards of numerous pharmaceutical companies with an interest in psoriasis therapies.
Although the phase II data are certainly encouraging, it is far too early to speculate as to the future of the two new anti-IL-17 biologics. That must await the outcome of the far larger and longer-term phase III studies, Dr. Kristian Reich said in an interview.
In particular, the issue of major adverse cardiovascular events is a potential concern with all agents that target IL-17, given the earlier experience with briakinumab. Development of the fully human monoclonal antibody that was directed against IL-12/23 was abandoned because of cardiovascular issues in the midst of phase III development, added Dr. Reich.
"Those of us who are developing new drugs for our armamentarium find we are in a perfect situation, with at least three interesting antibodies being developed: secukinumab, AMG 827, and the IL-23p19 antibody. Together, with ustekinumab, we now have a group of four antibodies, all of which influence the IL-23/Th17 pathway. It will be very interesting to see how good they are in taking care of psoriasis patients," he said.
Dr. Reich is the medical director of the Dermatologikum Hamburg. He has been involved in studies of all four agents and is on the advisory boards of numerous pharmaceutical companies with an interest in psoriasis therapies.
LISBON – Validation of the interleukin-17 cytokine family in psoriasis pathophysiology has gotten a boost from positive, phase II clinical trials involving two novel biologic agents.
The double-blind, placebo-controlled, phase II studies documented rapid and marked improvement in patients who had moderate to severe plaque psoriasis and were treated with secukinumab or AMG 827.
Roughly 80% of patients who were randomized to the maximum dose of either biologic experienced at least a PASI 75 (that is, improvement of 75% as measured by the Psoriasis Area and Severity Index) at 12 weeks. Those are efficacy rates in excess of the improvement obtainable with the earlier-generation biologics that targeted tumor necrosis factor–alpha, according to Dr. Kim A. Papp, who presented the data on both drugs at the annual congress of the European Academy of Dermatology and Venereology.
"This is a very robust, profound response suggesting that we’re really getting to the fundamentals of what’s driving psoriasis," Dr. Papp said.
Secukinumab is the agent further along in the developmental pipeline. A phase III clinical trial is already underway on the strength of three phase II studies presented at the congress.
Secukinumab is a fully human monoclonal antibody targeting IL-17A, a key member of the IL-17 cytokine family. The sequence of pathophysiologic events in psoriasis, as understood today, is that IL-23 induces activated Th17 cells, which in lesional skin express IL-17, in turn eliciting the production of proinflammatory cytokines by keratinocytes and keratinocyte hyperproliferation. IL-17A is one of several types of IL-17 that bind to the IL-17 receptor.
In contrast, AMG 827 is a human monoclonal antibody that blocks the IL-17 receptor itself, explained Dr. Papp, director of research at Probity Medical Research Inc. in Waterloo, Ont.
Secukinumab: Study 1
Dr. Papp presented the results of two of the three phase II studies of secukinumab. One study randomized 125 patients to subcutaneous secukinumab of 150 mg, 75 mg, or 25 mg once monthly for 3 months; to a single 25-mg dose; or to placebo.
The primary end point (PASI 75 response rate at 12 weeks) was 81%, 57%, 19%, 3%, and 9%, respectively. PASI 90 (that is, an improvement of 90% on the PASI) response rates were 52%, 19%, 8%, 0%, and 5%, respectively. Investigator Global Assessment scores of clear or almost clear at 12 weeks were achieved in 48% of patients in the 150-mg group and in 33% of those who received 75 mg, which were significantly better ratings than the 0%-12% rates in the other study arms.
Secukinumab: Study 2
The second secukinumab phase II study that was presented by Dr. Papp examined possible intravenous induction doses. The 100 participants were randomized to 3 mg/kg given on day 1; to 10 mg/kg on day 1; to 10 mg/kg on days 1, 15, and 29; or to placebo. The PASI 75 rates at 12 weeks were 40%, 75%, 83%, and 10%, respectively. The PASI 90 response rates were 10%, 54%, 76%, and 0%.
Secukinumab: Study 3
Dr. Phoebe A. Rich presented the third secukinumab phase II trial, which aimed to find the best dosing regimen. The study included 404 patients at 63 centers in seven countries who were randomized 1:2:2:1 to subcutaneous placebo; to a single 150-mg dose at week 0; to 150 mg at weeks 0, 4, and 8; or to 150 mg at weeks 0, 1, 2, and 4.
The treatment arm with dosing at weeks 0, 1, 2 and 4 was the winner, with a PASI 75 response rate of 55% at week 12, compared with 42% with dosing at weeks 0, 4, and 8; 11% for a single dose; and 2% with placebo. The corresponding PASI 90 rates were 32%, 17%, 3%, and 2%, added Dr. Phoebe of the Oregon Dermatology and Research Center, Portland.
None of these relatively brief trials suggested any safety signals. The side effect pattern was basically the same as in the placebo arms, according to the investigators.
AMG 827
Dr. Papp also presented the first phase II, randomized, double-blind trial of AMG 827. It involved 198 patients who were randomized to subcutaneous AMG 827 at 280 mg monthly; to 70, 140, or 210 mg every 2 weeks; or to placebo. The primary end point was the PASI 75 response rate at week 12. It was highest (83%) in patients who received 210 mg every 2 weeks.
Interestingly, nearly all of the PASI 75 responders were also PASI 90 responders. The PASI 90 and PASI 100 response rates in the group taking 210 mg every 2 weeks were 75% and 63%, respectively. Again, as for secukinumab, the safety profile was unremarkable.
The response waned 4-10 weeks after the last dose of AMG 827. This took the form of a gradual, progressive relapse rather than an abrupt rebound, noted Dr. Papp.
Dr. Papp said that the large turnout to his presentation at the meeting, "shows the interest and excitement that surrounds what I think is a new adventure and really a new revolution in the understanding and treatment of psoriasis."
Dr. Papp is on the advisory boards of Novartis, which is developing secukinumab, and Amgen, manufacturer of AMG 827. He is also an advisor to many other pharmaceutical companies developing drugs for psoriasis. Dr. Rich is also on the advisory board of Novartis and other companies that are developing drugs for psoriasis.
LISBON – Validation of the interleukin-17 cytokine family in psoriasis pathophysiology has gotten a boost from positive, phase II clinical trials involving two novel biologic agents.
The double-blind, placebo-controlled, phase II studies documented rapid and marked improvement in patients who had moderate to severe plaque psoriasis and were treated with secukinumab or AMG 827.
Roughly 80% of patients who were randomized to the maximum dose of either biologic experienced at least a PASI 75 (that is, improvement of 75% as measured by the Psoriasis Area and Severity Index) at 12 weeks. Those are efficacy rates in excess of the improvement obtainable with the earlier-generation biologics that targeted tumor necrosis factor–alpha, according to Dr. Kim A. Papp, who presented the data on both drugs at the annual congress of the European Academy of Dermatology and Venereology.
"This is a very robust, profound response suggesting that we’re really getting to the fundamentals of what’s driving psoriasis," Dr. Papp said.
Secukinumab is the agent further along in the developmental pipeline. A phase III clinical trial is already underway on the strength of three phase II studies presented at the congress.
Secukinumab is a fully human monoclonal antibody targeting IL-17A, a key member of the IL-17 cytokine family. The sequence of pathophysiologic events in psoriasis, as understood today, is that IL-23 induces activated Th17 cells, which in lesional skin express IL-17, in turn eliciting the production of proinflammatory cytokines by keratinocytes and keratinocyte hyperproliferation. IL-17A is one of several types of IL-17 that bind to the IL-17 receptor.
In contrast, AMG 827 is a human monoclonal antibody that blocks the IL-17 receptor itself, explained Dr. Papp, director of research at Probity Medical Research Inc. in Waterloo, Ont.
Secukinumab: Study 1
Dr. Papp presented the results of two of the three phase II studies of secukinumab. One study randomized 125 patients to subcutaneous secukinumab of 150 mg, 75 mg, or 25 mg once monthly for 3 months; to a single 25-mg dose; or to placebo.
The primary end point (PASI 75 response rate at 12 weeks) was 81%, 57%, 19%, 3%, and 9%, respectively. PASI 90 (that is, an improvement of 90% on the PASI) response rates were 52%, 19%, 8%, 0%, and 5%, respectively. Investigator Global Assessment scores of clear or almost clear at 12 weeks were achieved in 48% of patients in the 150-mg group and in 33% of those who received 75 mg, which were significantly better ratings than the 0%-12% rates in the other study arms.
Secukinumab: Study 2
The second secukinumab phase II study that was presented by Dr. Papp examined possible intravenous induction doses. The 100 participants were randomized to 3 mg/kg given on day 1; to 10 mg/kg on day 1; to 10 mg/kg on days 1, 15, and 29; or to placebo. The PASI 75 rates at 12 weeks were 40%, 75%, 83%, and 10%, respectively. The PASI 90 response rates were 10%, 54%, 76%, and 0%.
Secukinumab: Study 3
Dr. Phoebe A. Rich presented the third secukinumab phase II trial, which aimed to find the best dosing regimen. The study included 404 patients at 63 centers in seven countries who were randomized 1:2:2:1 to subcutaneous placebo; to a single 150-mg dose at week 0; to 150 mg at weeks 0, 4, and 8; or to 150 mg at weeks 0, 1, 2, and 4.
The treatment arm with dosing at weeks 0, 1, 2 and 4 was the winner, with a PASI 75 response rate of 55% at week 12, compared with 42% with dosing at weeks 0, 4, and 8; 11% for a single dose; and 2% with placebo. The corresponding PASI 90 rates were 32%, 17%, 3%, and 2%, added Dr. Phoebe of the Oregon Dermatology and Research Center, Portland.
None of these relatively brief trials suggested any safety signals. The side effect pattern was basically the same as in the placebo arms, according to the investigators.
AMG 827
Dr. Papp also presented the first phase II, randomized, double-blind trial of AMG 827. It involved 198 patients who were randomized to subcutaneous AMG 827 at 280 mg monthly; to 70, 140, or 210 mg every 2 weeks; or to placebo. The primary end point was the PASI 75 response rate at week 12. It was highest (83%) in patients who received 210 mg every 2 weeks.
Interestingly, nearly all of the PASI 75 responders were also PASI 90 responders. The PASI 90 and PASI 100 response rates in the group taking 210 mg every 2 weeks were 75% and 63%, respectively. Again, as for secukinumab, the safety profile was unremarkable.
The response waned 4-10 weeks after the last dose of AMG 827. This took the form of a gradual, progressive relapse rather than an abrupt rebound, noted Dr. Papp.
Dr. Papp said that the large turnout to his presentation at the meeting, "shows the interest and excitement that surrounds what I think is a new adventure and really a new revolution in the understanding and treatment of psoriasis."
Dr. Papp is on the advisory boards of Novartis, which is developing secukinumab, and Amgen, manufacturer of AMG 827. He is also an advisor to many other pharmaceutical companies developing drugs for psoriasis. Dr. Rich is also on the advisory board of Novartis and other companies that are developing drugs for psoriasis.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Major Finding: Two new biologic agents directed against IL-17 achieved 12-week PASI 75 response rates of about 80%.
Data Source: Four double-blind, randomized, placebo-controlled, phase II clinical trials of secukinumab and AMG-827.
Disclosures: Presenters disclosed being paid clinical researchers for and on the advisory boards of numerous pharmaceutical companies developing psoriasis therapies.