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VIDEO: Biologics slowly taming metastatic melanoma
MAUI, HAWAII – Though costly, newer biologics increase 1-year survival with metastatic melanoma from perhaps 40% to more than 70%.
Among the latest are nivolumab and pembrolizumab, antibodies against PD-1 (programmed cell death) cell surface receptors that were approved in 2014 for unresectable melanoma no longer responding to other drugs; another anti-PD-1 is in development.
In this video interview at the 2015 Rheumatology Winter Clinical Symposium, Dr. George Martin of the Dermatology and Laser Center of Maui explains the latest developments and shares his excitement about them.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MAUI, HAWAII – Though costly, newer biologics increase 1-year survival with metastatic melanoma from perhaps 40% to more than 70%.
Among the latest are nivolumab and pembrolizumab, antibodies against PD-1 (programmed cell death) cell surface receptors that were approved in 2014 for unresectable melanoma no longer responding to other drugs; another anti-PD-1 is in development.
In this video interview at the 2015 Rheumatology Winter Clinical Symposium, Dr. George Martin of the Dermatology and Laser Center of Maui explains the latest developments and shares his excitement about them.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
MAUI, HAWAII – Though costly, newer biologics increase 1-year survival with metastatic melanoma from perhaps 40% to more than 70%.
Among the latest are nivolumab and pembrolizumab, antibodies against PD-1 (programmed cell death) cell surface receptors that were approved in 2014 for unresectable melanoma no longer responding to other drugs; another anti-PD-1 is in development.
In this video interview at the 2015 Rheumatology Winter Clinical Symposium, Dr. George Martin of the Dermatology and Laser Center of Maui explains the latest developments and shares his excitement about them.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT RWCS 2015
Melanoma incidence highest in Oregon, lowest in Texas in 2015
Projections for the number of new melanoma cases in 2015 give Texas the lowest estimated incidence and Oregon the highest, according to a report from the American Cancer Society.
Texas is expected to have 2,410 new cases of melanoma this year, for an incidence of 8.9 cases per 100,000 people. Oregon’s projected 1,480 melanoma cases for 2015 results in an incidence of 37.3 cases per 100,000 population. (The ACS projected the number of new cases, so incidences here are calculated via recent Census Bureau population estimates.)
After Texas, Louisiana should have the lowest melanoma rate at 11.6 per 100,000, followed by Arkansas and the District of Columbia, both at 12.1 per 100,000. On the upper end of the scale, Oregon will likely be followed by Washington, where the incidence for 2015 is expected to be 34.8 per 100,000, the ACS data show.
Using incidences (1995-2011) reported by the North American Association of Central Cancer Registries, the ACS projected that 73,870 new cases of melanoma will be diagnosed in the United States this year – meaning an overall incidence of 23.2 per 100,000, based on the same Census Bureau figures.
The ACS estimated that there will be 9,940 deaths from melanoma in 2015 – an incidence of 3.1 per 100,000 population – as well as 3,400 deaths from other forms of skin cancer, not including basal cell and squamous cell carcinomas.
Projections for the number of new melanoma cases in 2015 give Texas the lowest estimated incidence and Oregon the highest, according to a report from the American Cancer Society.
Texas is expected to have 2,410 new cases of melanoma this year, for an incidence of 8.9 cases per 100,000 people. Oregon’s projected 1,480 melanoma cases for 2015 results in an incidence of 37.3 cases per 100,000 population. (The ACS projected the number of new cases, so incidences here are calculated via recent Census Bureau population estimates.)
After Texas, Louisiana should have the lowest melanoma rate at 11.6 per 100,000, followed by Arkansas and the District of Columbia, both at 12.1 per 100,000. On the upper end of the scale, Oregon will likely be followed by Washington, where the incidence for 2015 is expected to be 34.8 per 100,000, the ACS data show.
Using incidences (1995-2011) reported by the North American Association of Central Cancer Registries, the ACS projected that 73,870 new cases of melanoma will be diagnosed in the United States this year – meaning an overall incidence of 23.2 per 100,000, based on the same Census Bureau figures.
The ACS estimated that there will be 9,940 deaths from melanoma in 2015 – an incidence of 3.1 per 100,000 population – as well as 3,400 deaths from other forms of skin cancer, not including basal cell and squamous cell carcinomas.
Projections for the number of new melanoma cases in 2015 give Texas the lowest estimated incidence and Oregon the highest, according to a report from the American Cancer Society.
Texas is expected to have 2,410 new cases of melanoma this year, for an incidence of 8.9 cases per 100,000 people. Oregon’s projected 1,480 melanoma cases for 2015 results in an incidence of 37.3 cases per 100,000 population. (The ACS projected the number of new cases, so incidences here are calculated via recent Census Bureau population estimates.)
After Texas, Louisiana should have the lowest melanoma rate at 11.6 per 100,000, followed by Arkansas and the District of Columbia, both at 12.1 per 100,000. On the upper end of the scale, Oregon will likely be followed by Washington, where the incidence for 2015 is expected to be 34.8 per 100,000, the ACS data show.
Using incidences (1995-2011) reported by the North American Association of Central Cancer Registries, the ACS projected that 73,870 new cases of melanoma will be diagnosed in the United States this year – meaning an overall incidence of 23.2 per 100,000, based on the same Census Bureau figures.
The ACS estimated that there will be 9,940 deaths from melanoma in 2015 – an incidence of 3.1 per 100,000 population – as well as 3,400 deaths from other forms of skin cancer, not including basal cell and squamous cell carcinomas.
Overall survival plateaus at 3 years for ipilimumab-treated melanoma patients
Among patients with advanced melanoma who were treated with ipilimumab, about 20%-26% survived to 3 years, and these patients are likely to have a good long-term outcome, according to a pooled analysis of survival data published online Feb. 9 in the Journal of Clinical Oncology.
Investigators pooled data from ten prospective (including two phase III trials) and two retrospective studies with a total of 1,257 previously treated and 604 treatment-naive patients. At least 3 years after receiving ipilimumab, 254 patients were still alive, with a median follow up for this subset of 69 months. Around year 3, the Kaplan-Meier overall survival (OS) curve began to plateau and extended to 9.9 years for the longest survival follow-up.
“These results suggest that the majority of patients who reached this milestone time point had a low risk of death thereafter,” wrote Dr. Dirk Schadendorf and his associates (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.56.2736]).
Compared with patients who were previously treated, treatment-naive patients had a higher median overall survival (13.5 months [95% confidence interval, 11.9-15.4] vs. 10.7 months [9.6-11.4]) and higher 3-year-survival rates (26% [21%-30%] vs. 20% [18%-23%]). No definitive conclusion could be drawn from this observation, however, since nonrandomized subsets were used for this analysis. Subset analysis by dose showed similar median OS and 3-year survival rates for ipilimumab 3 mg/kg, 10 mg/kg, and other dosing regimens.
The researchers expanded the study to include overall survival (OS) data from 2,985 patients enrolled in a U.S. multicenter, open-label, expanded-access treatment protocol (EAP). This group included patients with poorer prognostic factors, some of whom were ineligible for clinical trials. The expanded group showed a lower median OS of 9.5 months and 3 year–survival rate of 21%, with the familiar OS curve plateau around 3 years that extended up to 10 years in some patients.
While this analysis only examined overall survival rates, individual ipilimumab studies that tracked patient responses to the drug have shown that some proportion of long-term survivors did not achieve a response. Identifying the specific disease characteristics of the long-term survivors will require further study.
“Considering the historic median OS of approximately 8-10 months and a 5-year survival rate of approximately 10% in advanced melanoma, the results presented herein are encouraging for patients diagnosed with this aggressive disease,” the authors wrote.
Dr. Schadendorf and his associates demonstrate a plateau in the survival curve of ipilimumab-treated patients beginning at about 3 years and representing about 21% of the treatment group. The curve suggests that those who survive to 3 years are highly likely to have a good long-term outcome, which provides a strong motivating factor in the decision to consider ipilimumab treatment. While pooled data adds information far beyond individual trials, a major drawback lies in the loss of control data necessary to isolate the added benefit of the study drug.
An indirect comparison using historic control series, in this case a large cohort documented in the American Joint Committee on Cancer (AJCC) Melanoma Staging Database, can substitute for missing control data in the pooled analysis. Reviewing data for stage IIIc and IV patients, the overall survival Kaplan-Meier curves in this population also show a plateau, but much later than that reported for ipilimumab, at beyond 8 years.
The AJCC melanoma classification gives survival rates at 3, 5, and 10 years of 19%, 13%, and 9%, respectively. Comparison with ipilimumab data suggests that survival at 3 years is similar, but thereafter improves with ipilimumab by 10% over other treatments that were available at the time. This difference is similar to the percentage of patients who achieved objective responses with ipilimumab. Although assessing response rate and progression-free survival in patients treated with ipilimumab presents challenges, the long-term benefits of ipilimumab could be better ascertained if information on the number of patients in the 21% plateau who were disease free or stably maintaining response had been collected.
Evaluation of long-term benefits of ipilimumab should consider toxicities and costs, as it is one of the most costly systemic therapies used for cancer treatment. The phase III trial using the drug at 3 mg/kg demonstrated that the large majority of patients had no serious adverse effects. If older patients and those with advanced disease are candidates, then the 10%-15% of grade 3 or 4 adverse events may translate to hospitalization and added expense, putting health regulatory systems in the position to deny widespread use of the agent despite proven benefit.
As the first agent to benefit overall survival of patients with advanced melanoma, ipilimumab may pave the way to broader improvements in a larger proportion of patients by combining with targeted therapies, such as BRAF and MEK inhibitors, and other new immunotherapies, such as anti-PD-1 antibodies.
Dr. Antoni Ribas is an oncologist with the Jonsson Comprehensive Cancer Center, Los Angles, and Dr. Keith T. Flaherty is an oncologist with Massachusetts General Hospital Cancer Center, Boston. These remarks were part of an editorial accompanying the report (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.56.2736]). Dr. Ribas has an advisory role with Merck, Amgen, Novartis, GlaxoSmithKline, and Genentech/Roche. Dr. Flaherty has an advisory role with GlaxoSmithKline, Genentech/Roche, Novartis, and Merck.
Dr. Schadendorf and his associates demonstrate a plateau in the survival curve of ipilimumab-treated patients beginning at about 3 years and representing about 21% of the treatment group. The curve suggests that those who survive to 3 years are highly likely to have a good long-term outcome, which provides a strong motivating factor in the decision to consider ipilimumab treatment. While pooled data adds information far beyond individual trials, a major drawback lies in the loss of control data necessary to isolate the added benefit of the study drug.
An indirect comparison using historic control series, in this case a large cohort documented in the American Joint Committee on Cancer (AJCC) Melanoma Staging Database, can substitute for missing control data in the pooled analysis. Reviewing data for stage IIIc and IV patients, the overall survival Kaplan-Meier curves in this population also show a plateau, but much later than that reported for ipilimumab, at beyond 8 years.
The AJCC melanoma classification gives survival rates at 3, 5, and 10 years of 19%, 13%, and 9%, respectively. Comparison with ipilimumab data suggests that survival at 3 years is similar, but thereafter improves with ipilimumab by 10% over other treatments that were available at the time. This difference is similar to the percentage of patients who achieved objective responses with ipilimumab. Although assessing response rate and progression-free survival in patients treated with ipilimumab presents challenges, the long-term benefits of ipilimumab could be better ascertained if information on the number of patients in the 21% plateau who were disease free or stably maintaining response had been collected.
Evaluation of long-term benefits of ipilimumab should consider toxicities and costs, as it is one of the most costly systemic therapies used for cancer treatment. The phase III trial using the drug at 3 mg/kg demonstrated that the large majority of patients had no serious adverse effects. If older patients and those with advanced disease are candidates, then the 10%-15% of grade 3 or 4 adverse events may translate to hospitalization and added expense, putting health regulatory systems in the position to deny widespread use of the agent despite proven benefit.
As the first agent to benefit overall survival of patients with advanced melanoma, ipilimumab may pave the way to broader improvements in a larger proportion of patients by combining with targeted therapies, such as BRAF and MEK inhibitors, and other new immunotherapies, such as anti-PD-1 antibodies.
Dr. Antoni Ribas is an oncologist with the Jonsson Comprehensive Cancer Center, Los Angles, and Dr. Keith T. Flaherty is an oncologist with Massachusetts General Hospital Cancer Center, Boston. These remarks were part of an editorial accompanying the report (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.56.2736]). Dr. Ribas has an advisory role with Merck, Amgen, Novartis, GlaxoSmithKline, and Genentech/Roche. Dr. Flaherty has an advisory role with GlaxoSmithKline, Genentech/Roche, Novartis, and Merck.
Dr. Schadendorf and his associates demonstrate a plateau in the survival curve of ipilimumab-treated patients beginning at about 3 years and representing about 21% of the treatment group. The curve suggests that those who survive to 3 years are highly likely to have a good long-term outcome, which provides a strong motivating factor in the decision to consider ipilimumab treatment. While pooled data adds information far beyond individual trials, a major drawback lies in the loss of control data necessary to isolate the added benefit of the study drug.
An indirect comparison using historic control series, in this case a large cohort documented in the American Joint Committee on Cancer (AJCC) Melanoma Staging Database, can substitute for missing control data in the pooled analysis. Reviewing data for stage IIIc and IV patients, the overall survival Kaplan-Meier curves in this population also show a plateau, but much later than that reported for ipilimumab, at beyond 8 years.
The AJCC melanoma classification gives survival rates at 3, 5, and 10 years of 19%, 13%, and 9%, respectively. Comparison with ipilimumab data suggests that survival at 3 years is similar, but thereafter improves with ipilimumab by 10% over other treatments that were available at the time. This difference is similar to the percentage of patients who achieved objective responses with ipilimumab. Although assessing response rate and progression-free survival in patients treated with ipilimumab presents challenges, the long-term benefits of ipilimumab could be better ascertained if information on the number of patients in the 21% plateau who were disease free or stably maintaining response had been collected.
Evaluation of long-term benefits of ipilimumab should consider toxicities and costs, as it is one of the most costly systemic therapies used for cancer treatment. The phase III trial using the drug at 3 mg/kg demonstrated that the large majority of patients had no serious adverse effects. If older patients and those with advanced disease are candidates, then the 10%-15% of grade 3 or 4 adverse events may translate to hospitalization and added expense, putting health regulatory systems in the position to deny widespread use of the agent despite proven benefit.
As the first agent to benefit overall survival of patients with advanced melanoma, ipilimumab may pave the way to broader improvements in a larger proportion of patients by combining with targeted therapies, such as BRAF and MEK inhibitors, and other new immunotherapies, such as anti-PD-1 antibodies.
Dr. Antoni Ribas is an oncologist with the Jonsson Comprehensive Cancer Center, Los Angles, and Dr. Keith T. Flaherty is an oncologist with Massachusetts General Hospital Cancer Center, Boston. These remarks were part of an editorial accompanying the report (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.56.2736]). Dr. Ribas has an advisory role with Merck, Amgen, Novartis, GlaxoSmithKline, and Genentech/Roche. Dr. Flaherty has an advisory role with GlaxoSmithKline, Genentech/Roche, Novartis, and Merck.
Among patients with advanced melanoma who were treated with ipilimumab, about 20%-26% survived to 3 years, and these patients are likely to have a good long-term outcome, according to a pooled analysis of survival data published online Feb. 9 in the Journal of Clinical Oncology.
Investigators pooled data from ten prospective (including two phase III trials) and two retrospective studies with a total of 1,257 previously treated and 604 treatment-naive patients. At least 3 years after receiving ipilimumab, 254 patients were still alive, with a median follow up for this subset of 69 months. Around year 3, the Kaplan-Meier overall survival (OS) curve began to plateau and extended to 9.9 years for the longest survival follow-up.
“These results suggest that the majority of patients who reached this milestone time point had a low risk of death thereafter,” wrote Dr. Dirk Schadendorf and his associates (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.56.2736]).
Compared with patients who were previously treated, treatment-naive patients had a higher median overall survival (13.5 months [95% confidence interval, 11.9-15.4] vs. 10.7 months [9.6-11.4]) and higher 3-year-survival rates (26% [21%-30%] vs. 20% [18%-23%]). No definitive conclusion could be drawn from this observation, however, since nonrandomized subsets were used for this analysis. Subset analysis by dose showed similar median OS and 3-year survival rates for ipilimumab 3 mg/kg, 10 mg/kg, and other dosing regimens.
The researchers expanded the study to include overall survival (OS) data from 2,985 patients enrolled in a U.S. multicenter, open-label, expanded-access treatment protocol (EAP). This group included patients with poorer prognostic factors, some of whom were ineligible for clinical trials. The expanded group showed a lower median OS of 9.5 months and 3 year–survival rate of 21%, with the familiar OS curve plateau around 3 years that extended up to 10 years in some patients.
While this analysis only examined overall survival rates, individual ipilimumab studies that tracked patient responses to the drug have shown that some proportion of long-term survivors did not achieve a response. Identifying the specific disease characteristics of the long-term survivors will require further study.
“Considering the historic median OS of approximately 8-10 months and a 5-year survival rate of approximately 10% in advanced melanoma, the results presented herein are encouraging for patients diagnosed with this aggressive disease,” the authors wrote.
Among patients with advanced melanoma who were treated with ipilimumab, about 20%-26% survived to 3 years, and these patients are likely to have a good long-term outcome, according to a pooled analysis of survival data published online Feb. 9 in the Journal of Clinical Oncology.
Investigators pooled data from ten prospective (including two phase III trials) and two retrospective studies with a total of 1,257 previously treated and 604 treatment-naive patients. At least 3 years after receiving ipilimumab, 254 patients were still alive, with a median follow up for this subset of 69 months. Around year 3, the Kaplan-Meier overall survival (OS) curve began to plateau and extended to 9.9 years for the longest survival follow-up.
“These results suggest that the majority of patients who reached this milestone time point had a low risk of death thereafter,” wrote Dr. Dirk Schadendorf and his associates (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.56.2736]).
Compared with patients who were previously treated, treatment-naive patients had a higher median overall survival (13.5 months [95% confidence interval, 11.9-15.4] vs. 10.7 months [9.6-11.4]) and higher 3-year-survival rates (26% [21%-30%] vs. 20% [18%-23%]). No definitive conclusion could be drawn from this observation, however, since nonrandomized subsets were used for this analysis. Subset analysis by dose showed similar median OS and 3-year survival rates for ipilimumab 3 mg/kg, 10 mg/kg, and other dosing regimens.
The researchers expanded the study to include overall survival (OS) data from 2,985 patients enrolled in a U.S. multicenter, open-label, expanded-access treatment protocol (EAP). This group included patients with poorer prognostic factors, some of whom were ineligible for clinical trials. The expanded group showed a lower median OS of 9.5 months and 3 year–survival rate of 21%, with the familiar OS curve plateau around 3 years that extended up to 10 years in some patients.
While this analysis only examined overall survival rates, individual ipilimumab studies that tracked patient responses to the drug have shown that some proportion of long-term survivors did not achieve a response. Identifying the specific disease characteristics of the long-term survivors will require further study.
“Considering the historic median OS of approximately 8-10 months and a 5-year survival rate of approximately 10% in advanced melanoma, the results presented herein are encouraging for patients diagnosed with this aggressive disease,” the authors wrote.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Ipilimumab-treated advanced melanoma patients alive at 3 years tend to have good long-term outcomes.
Major finding: Around year 3, the Kaplan-Meier OS curve began to plateau and extended to 9.9 years for the longest survival follow-up.
Data source: Pooled overall survival data from 12 studies including 1,861 ipilimumab-treated patients with advanced melanoma.
Disclosures: Dr. Schadendorf disclosed that he is a consultant for Bristol-Myers Squibb. Bristol-Myers Squibb sponsored this study.
Melanoma pathogenesis in patient reveals phenotype-genotype paradox
A melanoma in a dysplastic nevus contained a phenotype-genotype disagreement confounding the exclusive significance of BRAF and NRAS mutations in melanoma pathogenesis, according to Dr. Jean-Marie Tan and associates.
A man in his 50s was diagnosed with a melanoma in a dysplastic nevus after being admitted with a irregularly pigmented melanocytic lesion. Microbiopsy specimens were taken across the lesion and genotyping was carried out on DNA samples for BRAF and NRAS mutations. The melanoma showed only BRAF wild-type, while the dysplastic nevus showed both BRAF wild-type and BRAF V600E mutations. Sequencing in all DNA samples revealed NRAS wild-type genotype, the researchers found.
These conflicting results indicate further studies are required to investigate the importance of other candidate genes linked to melanomagenesis, the investigators concluded.
Read the full article at JAMA Dermatology (doi:10.1001/jamadermatol.2014.3775).
A melanoma in a dysplastic nevus contained a phenotype-genotype disagreement confounding the exclusive significance of BRAF and NRAS mutations in melanoma pathogenesis, according to Dr. Jean-Marie Tan and associates.
A man in his 50s was diagnosed with a melanoma in a dysplastic nevus after being admitted with a irregularly pigmented melanocytic lesion. Microbiopsy specimens were taken across the lesion and genotyping was carried out on DNA samples for BRAF and NRAS mutations. The melanoma showed only BRAF wild-type, while the dysplastic nevus showed both BRAF wild-type and BRAF V600E mutations. Sequencing in all DNA samples revealed NRAS wild-type genotype, the researchers found.
These conflicting results indicate further studies are required to investigate the importance of other candidate genes linked to melanomagenesis, the investigators concluded.
Read the full article at JAMA Dermatology (doi:10.1001/jamadermatol.2014.3775).
A melanoma in a dysplastic nevus contained a phenotype-genotype disagreement confounding the exclusive significance of BRAF and NRAS mutations in melanoma pathogenesis, according to Dr. Jean-Marie Tan and associates.
A man in his 50s was diagnosed with a melanoma in a dysplastic nevus after being admitted with a irregularly pigmented melanocytic lesion. Microbiopsy specimens were taken across the lesion and genotyping was carried out on DNA samples for BRAF and NRAS mutations. The melanoma showed only BRAF wild-type, while the dysplastic nevus showed both BRAF wild-type and BRAF V600E mutations. Sequencing in all DNA samples revealed NRAS wild-type genotype, the researchers found.
These conflicting results indicate further studies are required to investigate the importance of other candidate genes linked to melanomagenesis, the investigators concluded.
Read the full article at JAMA Dermatology (doi:10.1001/jamadermatol.2014.3775).
Xerosis is significant risk during targeted anticancer treatments
Patients receiving targeted anticancer treatments are at a significant risk of developing xerosis, or abnormal dryness, according to Dr. Johannah Valentine and her associates.
In a systematic review and meta-analysis of clinical trials involving 58 targeted agents, nearly 18% of all patients developed xerosis, with 1% of patients developing high-grade xerosis. The incidence may be affected by age, concomitant medications, comorbidities, and underlying malignancies or skin conditions, and reporting may vary among physicians and institutions, the researchers said.
Patients should be counseled and treated early for this symptom to prevent suboptimal dosing and quality-of-life impairment, the investigators recommended.
Read the full article at the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2014.12.010).
Patients receiving targeted anticancer treatments are at a significant risk of developing xerosis, or abnormal dryness, according to Dr. Johannah Valentine and her associates.
In a systematic review and meta-analysis of clinical trials involving 58 targeted agents, nearly 18% of all patients developed xerosis, with 1% of patients developing high-grade xerosis. The incidence may be affected by age, concomitant medications, comorbidities, and underlying malignancies or skin conditions, and reporting may vary among physicians and institutions, the researchers said.
Patients should be counseled and treated early for this symptom to prevent suboptimal dosing and quality-of-life impairment, the investigators recommended.
Read the full article at the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2014.12.010).
Patients receiving targeted anticancer treatments are at a significant risk of developing xerosis, or abnormal dryness, according to Dr. Johannah Valentine and her associates.
In a systematic review and meta-analysis of clinical trials involving 58 targeted agents, nearly 18% of all patients developed xerosis, with 1% of patients developing high-grade xerosis. The incidence may be affected by age, concomitant medications, comorbidities, and underlying malignancies or skin conditions, and reporting may vary among physicians and institutions, the researchers said.
Patients should be counseled and treated early for this symptom to prevent suboptimal dosing and quality-of-life impairment, the investigators recommended.
Read the full article at the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2014.12.010).
Manage Your Dermatology Practice: Managing Difficult Patient Encounters
Difficult patient encounters in the dermatology office can be navigated through honest physician-patient communication regarding problems within the office and insurance coverage. Dr. Gary Goldenberg provides tips on communicating with patients about cosmetic procedures that may be noncovered services as well as diagnoses such as melanoma and psoriasis. He also advises how to work through a long list of questions patients may bring to their visit.
Difficult patient encounters in the dermatology office can be navigated through honest physician-patient communication regarding problems within the office and insurance coverage. Dr. Gary Goldenberg provides tips on communicating with patients about cosmetic procedures that may be noncovered services as well as diagnoses such as melanoma and psoriasis. He also advises how to work through a long list of questions patients may bring to their visit.
Difficult patient encounters in the dermatology office can be navigated through honest physician-patient communication regarding problems within the office and insurance coverage. Dr. Gary Goldenberg provides tips on communicating with patients about cosmetic procedures that may be noncovered services as well as diagnoses such as melanoma and psoriasis. He also advises how to work through a long list of questions patients may bring to their visit.
Teledermoscopy referrals surpass paper for managing skin cancer patients
Smartphone teledermoscopy referrals were faster and allowed for more efficient management of patients with skin cancer, compared with paper referrals, according to Dr. Alexander Börve of the University of Gothenburg, Sweden, and his associates.
The waiting time was significantly shorter using teledermoscopy for patients with various melanomas and carcinomas when surgical treatment was necessary. “Triage decisions were also more reliable with teledermoscopy, and over 40% of the teledermoscopy patients could potentially have avoided face-to-face visits,” the researchers noted (Acta. Derm. Venereol. 2015;95:186-90).
Less than 1% of teledermoscopy referrals were excluded because of poor image quality, they said.
Read the full article at Acta Dermato-Venereologica (doi:10.2340/00015555-1906).
Smartphone teledermoscopy referrals were faster and allowed for more efficient management of patients with skin cancer, compared with paper referrals, according to Dr. Alexander Börve of the University of Gothenburg, Sweden, and his associates.
The waiting time was significantly shorter using teledermoscopy for patients with various melanomas and carcinomas when surgical treatment was necessary. “Triage decisions were also more reliable with teledermoscopy, and over 40% of the teledermoscopy patients could potentially have avoided face-to-face visits,” the researchers noted (Acta. Derm. Venereol. 2015;95:186-90).
Less than 1% of teledermoscopy referrals were excluded because of poor image quality, they said.
Read the full article at Acta Dermato-Venereologica (doi:10.2340/00015555-1906).
Smartphone teledermoscopy referrals were faster and allowed for more efficient management of patients with skin cancer, compared with paper referrals, according to Dr. Alexander Börve of the University of Gothenburg, Sweden, and his associates.
The waiting time was significantly shorter using teledermoscopy for patients with various melanomas and carcinomas when surgical treatment was necessary. “Triage decisions were also more reliable with teledermoscopy, and over 40% of the teledermoscopy patients could potentially have avoided face-to-face visits,” the researchers noted (Acta. Derm. Venereol. 2015;95:186-90).
Less than 1% of teledermoscopy referrals were excluded because of poor image quality, they said.
Read the full article at Acta Dermato-Venereologica (doi:10.2340/00015555-1906).
Vitiligo indicates effective melanoma treatment, predicts survival benefit
The development of vitiligo in melanoma patients on immunotherapy may predict improved survival, according to findings from a systematic review and meta-analysis.
In 137 studies reported between 1995 and 2013 and including 5,737 patients with stage III to IV melanoma who were treated with immunotherapy, the pooled cumulative incidence of vitiligo was 3.4%. In those with vitiligo for whom individual patient data were available, both progression-free and overall survival were significantly improved, compared with those without vitiligo after researchers adjusted for age and sex (hazard ratio, 0.51 and 0.25, respectively), Dr. Hansje-Eva Teulings of the University of Amsterdam and her colleagues reported online Jan. 19 in the Journal of Clinical Oncology.
Immune-related effects after melanoma immunotherapy have been linked to increased clinical efficacy. Vitiligo, which results from “strong antimelanoma immunity that also targets healthy melanocytes as a result of shared expression melanocyte differentiation antigens,” is no exception, but it was unclear whether data from individual studies showing tumor regression and improved survival in those with vitiligo could be extrapolated to all immunotherapy studies, the investigators explained (J. Clin. Oncol. 2015 Jan. 19 [doi:10.1200/JCO.2014.57.4756]).
The current findings highlight the significance of vitiligo as a clinical marker for effective antimelanoma immunity and for improved clinical outcome, they said, concluding that “more awareness of vitiligo induction in patients with melanoma by oncologists may contribute to better recognition of patients with effective antimelanoma immunity and may influence their treatment options and prognosis.”
The development of vitiligo in melanoma patients on immunotherapy may predict improved survival, according to findings from a systematic review and meta-analysis.
In 137 studies reported between 1995 and 2013 and including 5,737 patients with stage III to IV melanoma who were treated with immunotherapy, the pooled cumulative incidence of vitiligo was 3.4%. In those with vitiligo for whom individual patient data were available, both progression-free and overall survival were significantly improved, compared with those without vitiligo after researchers adjusted for age and sex (hazard ratio, 0.51 and 0.25, respectively), Dr. Hansje-Eva Teulings of the University of Amsterdam and her colleagues reported online Jan. 19 in the Journal of Clinical Oncology.
Immune-related effects after melanoma immunotherapy have been linked to increased clinical efficacy. Vitiligo, which results from “strong antimelanoma immunity that also targets healthy melanocytes as a result of shared expression melanocyte differentiation antigens,” is no exception, but it was unclear whether data from individual studies showing tumor regression and improved survival in those with vitiligo could be extrapolated to all immunotherapy studies, the investigators explained (J. Clin. Oncol. 2015 Jan. 19 [doi:10.1200/JCO.2014.57.4756]).
The current findings highlight the significance of vitiligo as a clinical marker for effective antimelanoma immunity and for improved clinical outcome, they said, concluding that “more awareness of vitiligo induction in patients with melanoma by oncologists may contribute to better recognition of patients with effective antimelanoma immunity and may influence their treatment options and prognosis.”
The development of vitiligo in melanoma patients on immunotherapy may predict improved survival, according to findings from a systematic review and meta-analysis.
In 137 studies reported between 1995 and 2013 and including 5,737 patients with stage III to IV melanoma who were treated with immunotherapy, the pooled cumulative incidence of vitiligo was 3.4%. In those with vitiligo for whom individual patient data were available, both progression-free and overall survival were significantly improved, compared with those without vitiligo after researchers adjusted for age and sex (hazard ratio, 0.51 and 0.25, respectively), Dr. Hansje-Eva Teulings of the University of Amsterdam and her colleagues reported online Jan. 19 in the Journal of Clinical Oncology.
Immune-related effects after melanoma immunotherapy have been linked to increased clinical efficacy. Vitiligo, which results from “strong antimelanoma immunity that also targets healthy melanocytes as a result of shared expression melanocyte differentiation antigens,” is no exception, but it was unclear whether data from individual studies showing tumor regression and improved survival in those with vitiligo could be extrapolated to all immunotherapy studies, the investigators explained (J. Clin. Oncol. 2015 Jan. 19 [doi:10.1200/JCO.2014.57.4756]).
The current findings highlight the significance of vitiligo as a clinical marker for effective antimelanoma immunity and for improved clinical outcome, they said, concluding that “more awareness of vitiligo induction in patients with melanoma by oncologists may contribute to better recognition of patients with effective antimelanoma immunity and may influence their treatment options and prognosis.”
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Vitiligo appears to serve as a clinical marker for effective antimelanoma immunity and improved clinical outcome.
Major finding: Progression-free and overall survival were improved in patients who developed vitiligo (HR, 0.51 and 0.25, respectively).
Data source: A systematic review and meta-analysis of 139 studies including 5,737 patients.
Disclosures: Dr. Teulings reported having no disclosures.
Handheld device illuminates possible routes of melanoma metastases
Investigators using a handheld dermoscopy device that allows visualization of colors, structures, and patterns in skin lesions not evident to the naked eye were able to visualize nonblanching blue and red lines in a branched pattern in two patients with in-transit cutaneous melanoma metastases.
Dr. Michael A. Marchetti and his associates at Memorial Sloan Kettering Cancer Center, New York, reported the “intriguing” visualization of dissemination for cutaneous melanoma metastases in a letter to JAMA Dermatology.
In-transit cutaneous melanoma metastases are those located more than 2 cm from the primary melanoma, but not beyond the regional nodal basin.
The first patient had wide local excision of a primary cutaneous melanoma on the forehead, and a year later, received localized irradiation for satellite skin metastases. A year after that, skin examination revealed six blue macules on the scalp more than 2 cm from the excision scar. Dermoscopy revealed nonblanching bluish lines in a branched pattern. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal lymphatics, Dr. Marchetti and his associates reported (JAMA Dermatology 2015;103-5)
The second patient had a history of multiple primary melanomas, the most recent being one on the chest treated with wide local excision. At a follow-up visit 5 years later, skin examination revealed eight blue-gray macules on the chest, all more than 2 cm from the excision scar. Dermoscopy revealed nonblanching, red-bluish, fuzzy, branching lines. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal blood vessels, the investigators wrote.
Typical dermoscopic features of cutaneous melanoma metastases include peripheral gray spots, atypical vessels, and a blue nevus-like pattern. The histopathologic findings in these two cases suggest that the dermoscopic color differences correspond to unique microanatomic routes of melanoma dissemination, with blue and red-blue lines corresponding to lymphatic and hematogenous dissemination of tumors, respectively, they said.
“While the factors driving lymphatic vs. hematogenous in-transit dissemination of melanoma remain unknown, as do any differences in their biologic significance, our finding is an intriguing clinical/dermoscopic/histopathologic observation,” the investigators concluded.
lnikolaides@frontlinemedcom.com
On Twitter @nikolaideslaura
Investigators using a handheld dermoscopy device that allows visualization of colors, structures, and patterns in skin lesions not evident to the naked eye were able to visualize nonblanching blue and red lines in a branched pattern in two patients with in-transit cutaneous melanoma metastases.
Dr. Michael A. Marchetti and his associates at Memorial Sloan Kettering Cancer Center, New York, reported the “intriguing” visualization of dissemination for cutaneous melanoma metastases in a letter to JAMA Dermatology.
In-transit cutaneous melanoma metastases are those located more than 2 cm from the primary melanoma, but not beyond the regional nodal basin.
The first patient had wide local excision of a primary cutaneous melanoma on the forehead, and a year later, received localized irradiation for satellite skin metastases. A year after that, skin examination revealed six blue macules on the scalp more than 2 cm from the excision scar. Dermoscopy revealed nonblanching bluish lines in a branched pattern. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal lymphatics, Dr. Marchetti and his associates reported (JAMA Dermatology 2015;103-5)
The second patient had a history of multiple primary melanomas, the most recent being one on the chest treated with wide local excision. At a follow-up visit 5 years later, skin examination revealed eight blue-gray macules on the chest, all more than 2 cm from the excision scar. Dermoscopy revealed nonblanching, red-bluish, fuzzy, branching lines. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal blood vessels, the investigators wrote.
Typical dermoscopic features of cutaneous melanoma metastases include peripheral gray spots, atypical vessels, and a blue nevus-like pattern. The histopathologic findings in these two cases suggest that the dermoscopic color differences correspond to unique microanatomic routes of melanoma dissemination, with blue and red-blue lines corresponding to lymphatic and hematogenous dissemination of tumors, respectively, they said.
“While the factors driving lymphatic vs. hematogenous in-transit dissemination of melanoma remain unknown, as do any differences in their biologic significance, our finding is an intriguing clinical/dermoscopic/histopathologic observation,” the investigators concluded.
lnikolaides@frontlinemedcom.com
On Twitter @nikolaideslaura
Investigators using a handheld dermoscopy device that allows visualization of colors, structures, and patterns in skin lesions not evident to the naked eye were able to visualize nonblanching blue and red lines in a branched pattern in two patients with in-transit cutaneous melanoma metastases.
Dr. Michael A. Marchetti and his associates at Memorial Sloan Kettering Cancer Center, New York, reported the “intriguing” visualization of dissemination for cutaneous melanoma metastases in a letter to JAMA Dermatology.
In-transit cutaneous melanoma metastases are those located more than 2 cm from the primary melanoma, but not beyond the regional nodal basin.
The first patient had wide local excision of a primary cutaneous melanoma on the forehead, and a year later, received localized irradiation for satellite skin metastases. A year after that, skin examination revealed six blue macules on the scalp more than 2 cm from the excision scar. Dermoscopy revealed nonblanching bluish lines in a branched pattern. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal lymphatics, Dr. Marchetti and his associates reported (JAMA Dermatology 2015;103-5)
The second patient had a history of multiple primary melanomas, the most recent being one on the chest treated with wide local excision. At a follow-up visit 5 years later, skin examination revealed eight blue-gray macules on the chest, all more than 2 cm from the excision scar. Dermoscopy revealed nonblanching, red-bluish, fuzzy, branching lines. Histopathologic examination of a skin biopsy confirmed in-transit metastatic melanoma with atypical melanocytes present in superficial dermal blood vessels, the investigators wrote.
Typical dermoscopic features of cutaneous melanoma metastases include peripheral gray spots, atypical vessels, and a blue nevus-like pattern. The histopathologic findings in these two cases suggest that the dermoscopic color differences correspond to unique microanatomic routes of melanoma dissemination, with blue and red-blue lines corresponding to lymphatic and hematogenous dissemination of tumors, respectively, they said.
“While the factors driving lymphatic vs. hematogenous in-transit dissemination of melanoma remain unknown, as do any differences in their biologic significance, our finding is an intriguing clinical/dermoscopic/histopathologic observation,” the investigators concluded.
lnikolaides@frontlinemedcom.com
On Twitter @nikolaideslaura
FROM JAMA DERMATOLOGY
MEK inhibitors can induce skin eruptions with distinctive duskiness
Case reports of unusual drug hypersensitivity to MEK inhibitors, involving skin eruptions with distinctive central duskiness, have been described online in JAMA Dermatology.
Three patients who were receiving different MEK inhibitors (selumetinib, cobimetinib, and trametinib) developed grade 2 or 3 eruptions, all associated with unique duskiness, reported Dr. Urvi Patel and associates at Washington University, St. Louis.
A 60-year-old man with pancreatic cancer who was receiving selumetinib as part of a clinical trial presented with a grade 2 generalized eruption and pruritus 12 days after initiating therapy. He had diffuse targetoid patches with central duskiness. Selumetinib and other study drugs were withheld, the patient was given topical corticosteroid treatment, and the eruption completely resolved after 4 weeks. The patient did not restart the study drugs because of an elevated alkaline phosphatase level and fatigue.
A woman in her 40s who was receiving cobimetinib and other medication for metastatic melanoma developed grade 2 coalescing urticarial patches with surrounding duskiness on day 28 of treatment. Histopathologic examination showed a superficial perivascular lymphocytic infiltrate with rare eosinophils. After treatment was halted for 7 days and a regimen of oral prednisone was started, cobimetinib therapy was reinstituted at a lower dose. There was no recurrence of the eruption 1 year after cobimetinib therapy was restarted, Dr. Patel and associates reported (JAMA Dermatol. 2015 Jan. 14 [doi:10.1001/jamadermatol.2014.3207]).
The third patient, a woman in her 50s with metastatic melanoma, developed a grade 3 eruption 7 weeks into trametinib treatment together with another drug. The worsening urticarial patches and plaques had surrounding diffuse duskiness. After trametinib treatment was withheld for a week, and a regimen of oral prednisone was begun, trametinib therapy was restarted and the eruption did not return.
“As shown in our patients, successful treatment of this MEK inhibitor–associated cutaneous eruption can include a drug holiday and oral corticosteroid therapy, with reinstitution of the drug at a lower dose without recurrence,” Dr. Patel and his associates wrote.
MEK inhibitors target the mitogen-activated protein kinase pathway. Trametinib has been approved for treating advanced melanoma, and more than a dozen other MEK inhibitors are in clinical trials (including selumetinib and cobimetinib) for treatment of melanoma and other solid-organ malignant neoplasms, including pancreatic, hepatocellular, colorectal, and non–small cell lung cancer, the authors noted.
lnikolaides@frontlinemedcom.com
On Twitter @nikolaideslaura
Case reports of unusual drug hypersensitivity to MEK inhibitors, involving skin eruptions with distinctive central duskiness, have been described online in JAMA Dermatology.
Three patients who were receiving different MEK inhibitors (selumetinib, cobimetinib, and trametinib) developed grade 2 or 3 eruptions, all associated with unique duskiness, reported Dr. Urvi Patel and associates at Washington University, St. Louis.
A 60-year-old man with pancreatic cancer who was receiving selumetinib as part of a clinical trial presented with a grade 2 generalized eruption and pruritus 12 days after initiating therapy. He had diffuse targetoid patches with central duskiness. Selumetinib and other study drugs were withheld, the patient was given topical corticosteroid treatment, and the eruption completely resolved after 4 weeks. The patient did not restart the study drugs because of an elevated alkaline phosphatase level and fatigue.
A woman in her 40s who was receiving cobimetinib and other medication for metastatic melanoma developed grade 2 coalescing urticarial patches with surrounding duskiness on day 28 of treatment. Histopathologic examination showed a superficial perivascular lymphocytic infiltrate with rare eosinophils. After treatment was halted for 7 days and a regimen of oral prednisone was started, cobimetinib therapy was reinstituted at a lower dose. There was no recurrence of the eruption 1 year after cobimetinib therapy was restarted, Dr. Patel and associates reported (JAMA Dermatol. 2015 Jan. 14 [doi:10.1001/jamadermatol.2014.3207]).
The third patient, a woman in her 50s with metastatic melanoma, developed a grade 3 eruption 7 weeks into trametinib treatment together with another drug. The worsening urticarial patches and plaques had surrounding diffuse duskiness. After trametinib treatment was withheld for a week, and a regimen of oral prednisone was begun, trametinib therapy was restarted and the eruption did not return.
“As shown in our patients, successful treatment of this MEK inhibitor–associated cutaneous eruption can include a drug holiday and oral corticosteroid therapy, with reinstitution of the drug at a lower dose without recurrence,” Dr. Patel and his associates wrote.
MEK inhibitors target the mitogen-activated protein kinase pathway. Trametinib has been approved for treating advanced melanoma, and more than a dozen other MEK inhibitors are in clinical trials (including selumetinib and cobimetinib) for treatment of melanoma and other solid-organ malignant neoplasms, including pancreatic, hepatocellular, colorectal, and non–small cell lung cancer, the authors noted.
lnikolaides@frontlinemedcom.com
On Twitter @nikolaideslaura
Case reports of unusual drug hypersensitivity to MEK inhibitors, involving skin eruptions with distinctive central duskiness, have been described online in JAMA Dermatology.
Three patients who were receiving different MEK inhibitors (selumetinib, cobimetinib, and trametinib) developed grade 2 or 3 eruptions, all associated with unique duskiness, reported Dr. Urvi Patel and associates at Washington University, St. Louis.
A 60-year-old man with pancreatic cancer who was receiving selumetinib as part of a clinical trial presented with a grade 2 generalized eruption and pruritus 12 days after initiating therapy. He had diffuse targetoid patches with central duskiness. Selumetinib and other study drugs were withheld, the patient was given topical corticosteroid treatment, and the eruption completely resolved after 4 weeks. The patient did not restart the study drugs because of an elevated alkaline phosphatase level and fatigue.
A woman in her 40s who was receiving cobimetinib and other medication for metastatic melanoma developed grade 2 coalescing urticarial patches with surrounding duskiness on day 28 of treatment. Histopathologic examination showed a superficial perivascular lymphocytic infiltrate with rare eosinophils. After treatment was halted for 7 days and a regimen of oral prednisone was started, cobimetinib therapy was reinstituted at a lower dose. There was no recurrence of the eruption 1 year after cobimetinib therapy was restarted, Dr. Patel and associates reported (JAMA Dermatol. 2015 Jan. 14 [doi:10.1001/jamadermatol.2014.3207]).
The third patient, a woman in her 50s with metastatic melanoma, developed a grade 3 eruption 7 weeks into trametinib treatment together with another drug. The worsening urticarial patches and plaques had surrounding diffuse duskiness. After trametinib treatment was withheld for a week, and a regimen of oral prednisone was begun, trametinib therapy was restarted and the eruption did not return.
“As shown in our patients, successful treatment of this MEK inhibitor–associated cutaneous eruption can include a drug holiday and oral corticosteroid therapy, with reinstitution of the drug at a lower dose without recurrence,” Dr. Patel and his associates wrote.
MEK inhibitors target the mitogen-activated protein kinase pathway. Trametinib has been approved for treating advanced melanoma, and more than a dozen other MEK inhibitors are in clinical trials (including selumetinib and cobimetinib) for treatment of melanoma and other solid-organ malignant neoplasms, including pancreatic, hepatocellular, colorectal, and non–small cell lung cancer, the authors noted.
lnikolaides@frontlinemedcom.com
On Twitter @nikolaideslaura
FROM JAMA DERMATOLOGY
Key clinical point: This MEK inhibitor–associated cutaneous eruption can be treated with a drug holiday and oral corticosteroid treatment, restarting the drug at a lower dose without recurrence.
Major finding: Three patients who were receiving different MEK inhibitors (selumetinib, cobimetinib, and trametinib) developed grade 2 or 3 eruptions, all associated with unique duskiness.
Data source: Three case studies of patients receiving different MEK inhibitors.
Disclosures: Dr. Lynn Cornelius has received a research grant from Genentech and is a clinical subinvestigator for GlaxoSmithKline. Dr. Milan J. Anadkat has received honoraria as a speaker and/or consultant from AstraZeneca, Bristol-Myers Squibb, Eisai, ImClone, and Therakos. No other disclosures were reported.