Melanoma

CHICAGO – Pairing the immune checkpoint inhibitors nivolumab and ipilimumab delivered deep and durable responses in patients with advanced metastatic melanoma, producing a 2-year overall survival rate of 79% among 53 patients.

"These are remarkable data even for a trial of this size in metastatic melanoma," noted Dr. Mario Sznol, a professor of medical oncology at Yale University, New Haven, Conn.

In a video interview at the annual meeting of the American Society for Clinical Oncology, Dr. Sznol discusses the study results, and he outlines how combinations of new agents with older treatments such as interferon and interleukin-2 may be used in the future.

CHICAGO – Pairing the immune checkpoint inhibitors nivolumab and ipilimumab delivered deep and durable responses in patients with advanced metastatic melanoma, producing a 2-year overall survival rate of 79% among 53 patients.

"These are remarkable data even for a trial of this size in metastatic melanoma," noted Dr. Mario Sznol, a professor of medical oncology at Yale University, New Haven, Conn.

In a video interview at the annual meeting of the American Society for Clinical Oncology, Dr. Sznol discusses the study results, and he outlines how combinations of new agents with older treatments such as interferon and interleukin-2 may be used in the future.

CHICAGO – Pairing the immune checkpoint inhibitors nivolumab and ipilimumab delivered deep and durable responses in patients with advanced metastatic melanoma, producing a 2-year overall survival rate of 79% among 53 patients.

"These are remarkable data even for a trial of this size in metastatic melanoma," noted Dr. Mario Sznol, a professor of medical oncology at Yale University, New Haven, Conn.

In a video interview at the annual meeting of the American Society for Clinical Oncology, Dr. Sznol discusses the study results, and he outlines how combinations of new agents with older treatments such as interferon and interleukin-2 may be used in the future.

CHICAGO – Advanced melanoma therapy – a field notorious for offering patients few drugs and little chance of survival – may be on the brink of an extraordinary transformation.

"There’s truly a revolution going in the immunotherapy of melanoma," explained Dr. Steven O’Day of the Beverly Hills (Calif.) Cancer Center.

In a video interview at the annual meeting of the American Society for Clinical Oncology, Dr. O’Day reviews the rapid developments in melanoma treatment options and the shift from a "nuclear bomb" approach to a more-targeted "cruise missile" mindset. He also highlights the parallels between the exceptional advances made in childhood leukemia treatment and new melanoma treatments such as ipilimumab and PD-1 inhibitors, and he discusses the new drugs’ ability to overcome a phenomenon that often defeats chemotherapy: cancer cell resistance.

CHICAGO – Advanced melanoma therapy – a field notorious for offering patients few drugs and little chance of survival – may be on the brink of an extraordinary transformation.

"There’s truly a revolution going in the immunotherapy of melanoma," explained Dr. Steven O’Day of the Beverly Hills (Calif.) Cancer Center.

In a video interview at the annual meeting of the American Society for Clinical Oncology, Dr. O’Day reviews the rapid developments in melanoma treatment options and the shift from a "nuclear bomb" approach to a more-targeted "cruise missile" mindset. He also highlights the parallels between the exceptional advances made in childhood leukemia treatment and new melanoma treatments such as ipilimumab and PD-1 inhibitors, and he discusses the new drugs’ ability to overcome a phenomenon that often defeats chemotherapy: cancer cell resistance.

CHICAGO – Advanced melanoma therapy – a field notorious for offering patients few drugs and little chance of survival – may be on the brink of an extraordinary transformation.

"There’s truly a revolution going in the immunotherapy of melanoma," explained Dr. Steven O’Day of the Beverly Hills (Calif.) Cancer Center.

In a video interview at the annual meeting of the American Society for Clinical Oncology, Dr. O’Day reviews the rapid developments in melanoma treatment options and the shift from a "nuclear bomb" approach to a more-targeted "cruise missile" mindset. He also highlights the parallels between the exceptional advances made in childhood leukemia treatment and new melanoma treatments such as ipilimumab and PD-1 inhibitors, and he discusses the new drugs’ ability to overcome a phenomenon that often defeats chemotherapy: cancer cell resistance.

CHICAGO – Results from a phase I study of investigational PD-1 antibody pembrolizumab may point the way toward higher treatment response rates and less toxicity in patients with advanced metastatic melanoma.

Of 411 patients who took pembrolizumab, 1-year overall survival was 69%, and 88% of patients who had a treatment response continued to have a response at 1 year, reported Dr. Antoni Ribas, professor of medicine at the University of California, Los Angeles.

In a video interview at the annual meeting of the American Society for Clinical Oncology, Dr. Ribas discussed the study results and explained how PD-1 antibodies help the immune system recognize and mount a more potent T-cell–mediated defense against melanoma.

CHICAGO – Results from a phase I study of investigational PD-1 antibody pembrolizumab may point the way toward higher treatment response rates and less toxicity in patients with advanced metastatic melanoma.

Of 411 patients who took pembrolizumab, 1-year overall survival was 69%, and 88% of patients who had a treatment response continued to have a response at 1 year, reported Dr. Antoni Ribas, professor of medicine at the University of California, Los Angeles.

In a video interview at the annual meeting of the American Society for Clinical Oncology, Dr. Ribas discussed the study results and explained how PD-1 antibodies help the immune system recognize and mount a more potent T-cell–mediated defense against melanoma.

CHICAGO – Results from a phase I study of investigational PD-1 antibody pembrolizumab may point the way toward higher treatment response rates and less toxicity in patients with advanced metastatic melanoma.

Of 411 patients who took pembrolizumab, 1-year overall survival was 69%, and 88% of patients who had a treatment response continued to have a response at 1 year, reported Dr. Antoni Ribas, professor of medicine at the University of California, Los Angeles.

In a video interview at the annual meeting of the American Society for Clinical Oncology, Dr. Ribas discussed the study results and explained how PD-1 antibodies help the immune system recognize and mount a more potent T-cell–mediated defense against melanoma.

CHICAGO – The combination of two immune checkpoint inhibitors, nivolumab and ipilimumab, has resulted in "unprecedented" 2-year overall survival rates for patients with metastatic melanoma, early study results show.

In an expanded phase I trial evaluating dosing, safety and efficacy of nivolumab and ipilimumab (Yervoy) either concurrently or in sequence, the 2-year overall survival for 53 patients in three concurrent dosing cohorts was 79%, reported Dr. Mario Sznol, a professor of medical oncology at Yale University, New Haven, Conn.

"We saw significant activity in patients with BRAF mutations, which means this is a very good option in addition to targeted therapy for patients who have BRAF mutations," Dr. Sznol said during a media briefing at the annual meeting of the American Society of Clinical Oncology.

"I almost feel like I’m looking at childhood leukemia survival curves, when we’re starting to approach an 80% plateau," commented Dr. Steven O’Day from the Beverly Hills (Calif.) Cancer Center, who moderated the briefing but was not involved in the study.

He cautioned that the study was small and that randomized, controlled phase III trials will be required before the full benefits of the combined therapies are evident.

Two checkpoints

Both agents are monoclonal antibodies directed against receptors in immune system checkpoints. Ipilimumab is a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor that acts at an early "brake" point in the immune response; nivolumab is a programmed cell death-1 (PD-1) inhibitor that serves as a late brake. By releasing the brakes, the drugs allow the immune system to operate full throttle against melanoma.

Ipilimumab is approved by the Food and Drug Administration for the treatment of metastatic melanoma. Nivolumab is an investigational agent that has been shown to have good antitumor activity in monotherapy.

"PD-1 and CTLA-4 both, as you\'ve heard before, are nonredundant checkpoints in T-cell differentiation and function, and there are several animal models that show synergy by combining these two agents," Dr. Sznol said in an oral abstract session.

As single agents, ipilimumab is associated with a 2-year overall survival rate of 24%, and nivolumab with a 2-year OS of 43%.

The investigators reported at ASCO 2013 and in the New England Journal of Medicine that the combined agents were associated with a 1-year OS of 82%.

Complex protocol

In the head-spinningly complex phase I dose-escalation study, patients with unresectable stage III or IV malignant melanoma were assigned to one of eight different dosing cohorts, looking at doses of nivolumab ranging from 0.3 to 10 mg/kg delivered in a 60 or 90 minute infusion every 2 or 3 weeks for up to 21 weeks, and to ipilimumab at doses ranging from 3 to 10 mg/kg delivered in 60- to 90-minute infusions every 3 weeks for 9 to 21 weeks of induction, followed by 84 to 96 weeks of maintenance therapy.

For the current report, Dr. Sznol and his colleagues looked at follow-up of 53 patients in dosing cohorts 1-3, all of whom received the drugs concurrently every 3 weeks for four doses, followed by nivolumab every 3 weeks for four doses, and then the combined agents every 12 weeks for eight doses. They also reported on a new, eighth cohort of 41 patients who received both drugs on the same induction schedule, followed by maintenance with nivolumab 3 mg/kg alone every 2 weeks until disease progression. This dosing schedule is being evaluated in phase II/III trials.

The overall response rate (ORR) for cohorts 1-3 was 42%, with 17% of patients having a complete response according to RECIST (Response Evaluation Criteria in Solid Tumors). In cohort 8, 40 of the 41 patients enrolled were evaluable for response, with an ORR of 43, and a 10% complete response rate (CRRs), although two of the CRRs were unconfirmed.

80% tumor shrinkage

In cohorts 1-3, 42% of patients had a reduction in tumor size of more than 80%, and many of these patients had complete or near-complete responses, Dr. Sznol said. Tumor shrinkage appeared similar in cohort 8, as shown on a waterfall plot, but Dr. Sznol did not report specifics about tumor dimensions in this group.

The median duration of responses in all four cohorts discussed has not been reached.

Grade 3 or 4 toxicities occurred in 62% of patients, with gastrointestinal side effects and elevated liver function tests occurring in 14% each, and increases in serum lipase in 15% and amylase in 6%. No new safety signals have emerged over 22 months of follow-up of patients in the initial cohorts, Dr. Sznol noted.

Dr. Jeffrey Weber of the Moffit Cancer Center in Tampa, Fla., the invited discussant, who has treated patients using the drugs in combination, commented that "Yes, you do see a large rate of patients with asymptomatic liver-function abnormalities that get better, and then you can retreat them."

Grade 3 elevated lipase or amylase may not require treatment, and grade 4 events may resolve with treatment interruption. Much of the toxicity occurs early with the concurrent regimen, and lessens during maintenance with nivolumab alone, he added.

Of the 94 patients in cohorts 1-3 and 8, 22 (23%) discontinued therapy due to treatment-related adverse events. One patient died from multiorgan failure associated with treatment-induced colitis; this patient was in cohort 8.

The study is supported by Bristol-Myers Squibb, Medarex, and Ono Pharma USA. Dr. Sznol disclosed consultant/advisory relationships with Bristol-Myers Squibb and several other companies. Dr. Weber disclosed consulting/advising, and received honoraria and research funding from Bristol-Myers Squibb and other companies. Dr. O’Day has received grants for research support from Bristol-Myers Squibb and Medarex, and he has served on the speakers bureau for Bristol-Myers Squibb.

CHICAGO – The combination of two immune checkpoint inhibitors, nivolumab and ipilimumab, has resulted in "unprecedented" 2-year overall survival rates for patients with metastatic melanoma, early study results show.

In an expanded phase I trial evaluating dosing, safety and efficacy of nivolumab and ipilimumab (Yervoy) either concurrently or in sequence, the 2-year overall survival for 53 patients in three concurrent dosing cohorts was 79%, reported Dr. Mario Sznol, a professor of medical oncology at Yale University, New Haven, Conn.

"We saw significant activity in patients with BRAF mutations, which means this is a very good option in addition to targeted therapy for patients who have BRAF mutations," Dr. Sznol said during a media briefing at the annual meeting of the American Society of Clinical Oncology.

"I almost feel like I’m looking at childhood leukemia survival curves, when we’re starting to approach an 80% plateau," commented Dr. Steven O’Day from the Beverly Hills (Calif.) Cancer Center, who moderated the briefing but was not involved in the study.

He cautioned that the study was small and that randomized, controlled phase III trials will be required before the full benefits of the combined therapies are evident.

Two checkpoints

Both agents are monoclonal antibodies directed against receptors in immune system checkpoints. Ipilimumab is a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor that acts at an early "brake" point in the immune response; nivolumab is a programmed cell death-1 (PD-1) inhibitor that serves as a late brake. By releasing the brakes, the drugs allow the immune system to operate full throttle against melanoma.

Ipilimumab is approved by the Food and Drug Administration for the treatment of metastatic melanoma. Nivolumab is an investigational agent that has been shown to have good antitumor activity in monotherapy.

"PD-1 and CTLA-4 both, as you\'ve heard before, are nonredundant checkpoints in T-cell differentiation and function, and there are several animal models that show synergy by combining these two agents," Dr. Sznol said in an oral abstract session.

As single agents, ipilimumab is associated with a 2-year overall survival rate of 24%, and nivolumab with a 2-year OS of 43%.

The investigators reported at ASCO 2013 and in the New England Journal of Medicine that the combined agents were associated with a 1-year OS of 82%.

Complex protocol

In the head-spinningly complex phase I dose-escalation study, patients with unresectable stage III or IV malignant melanoma were assigned to one of eight different dosing cohorts, looking at doses of nivolumab ranging from 0.3 to 10 mg/kg delivered in a 60 or 90 minute infusion every 2 or 3 weeks for up to 21 weeks, and to ipilimumab at doses ranging from 3 to 10 mg/kg delivered in 60- to 90-minute infusions every 3 weeks for 9 to 21 weeks of induction, followed by 84 to 96 weeks of maintenance therapy.

For the current report, Dr. Sznol and his colleagues looked at follow-up of 53 patients in dosing cohorts 1-3, all of whom received the drugs concurrently every 3 weeks for four doses, followed by nivolumab every 3 weeks for four doses, and then the combined agents every 12 weeks for eight doses. They also reported on a new, eighth cohort of 41 patients who received both drugs on the same induction schedule, followed by maintenance with nivolumab 3 mg/kg alone every 2 weeks until disease progression. This dosing schedule is being evaluated in phase II/III trials.

The overall response rate (ORR) for cohorts 1-3 was 42%, with 17% of patients having a complete response according to RECIST (Response Evaluation Criteria in Solid Tumors). In cohort 8, 40 of the 41 patients enrolled were evaluable for response, with an ORR of 43, and a 10% complete response rate (CRRs), although two of the CRRs were unconfirmed.

80% tumor shrinkage

In cohorts 1-3, 42% of patients had a reduction in tumor size of more than 80%, and many of these patients had complete or near-complete responses, Dr. Sznol said. Tumor shrinkage appeared similar in cohort 8, as shown on a waterfall plot, but Dr. Sznol did not report specifics about tumor dimensions in this group.

The median duration of responses in all four cohorts discussed has not been reached.

Grade 3 or 4 toxicities occurred in 62% of patients, with gastrointestinal side effects and elevated liver function tests occurring in 14% each, and increases in serum lipase in 15% and amylase in 6%. No new safety signals have emerged over 22 months of follow-up of patients in the initial cohorts, Dr. Sznol noted.

Dr. Jeffrey Weber of the Moffit Cancer Center in Tampa, Fla., the invited discussant, who has treated patients using the drugs in combination, commented that "Yes, you do see a large rate of patients with asymptomatic liver-function abnormalities that get better, and then you can retreat them."

Grade 3 elevated lipase or amylase may not require treatment, and grade 4 events may resolve with treatment interruption. Much of the toxicity occurs early with the concurrent regimen, and lessens during maintenance with nivolumab alone, he added.

Of the 94 patients in cohorts 1-3 and 8, 22 (23%) discontinued therapy due to treatment-related adverse events. One patient died from multiorgan failure associated with treatment-induced colitis; this patient was in cohort 8.

The study is supported by Bristol-Myers Squibb, Medarex, and Ono Pharma USA. Dr. Sznol disclosed consultant/advisory relationships with Bristol-Myers Squibb and several other companies. Dr. Weber disclosed consulting/advising, and received honoraria and research funding from Bristol-Myers Squibb and other companies. Dr. O’Day has received grants for research support from Bristol-Myers Squibb and Medarex, and he has served on the speakers bureau for Bristol-Myers Squibb.

CHICAGO – The combination of two immune checkpoint inhibitors, nivolumab and ipilimumab, has resulted in "unprecedented" 2-year overall survival rates for patients with metastatic melanoma, early study results show.

In an expanded phase I trial evaluating dosing, safety and efficacy of nivolumab and ipilimumab (Yervoy) either concurrently or in sequence, the 2-year overall survival for 53 patients in three concurrent dosing cohorts was 79%, reported Dr. Mario Sznol, a professor of medical oncology at Yale University, New Haven, Conn.

"We saw significant activity in patients with BRAF mutations, which means this is a very good option in addition to targeted therapy for patients who have BRAF mutations," Dr. Sznol said during a media briefing at the annual meeting of the American Society of Clinical Oncology.

"I almost feel like I’m looking at childhood leukemia survival curves, when we’re starting to approach an 80% plateau," commented Dr. Steven O’Day from the Beverly Hills (Calif.) Cancer Center, who moderated the briefing but was not involved in the study.

He cautioned that the study was small and that randomized, controlled phase III trials will be required before the full benefits of the combined therapies are evident.

Two checkpoints

Both agents are monoclonal antibodies directed against receptors in immune system checkpoints. Ipilimumab is a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor that acts at an early "brake" point in the immune response; nivolumab is a programmed cell death-1 (PD-1) inhibitor that serves as a late brake. By releasing the brakes, the drugs allow the immune system to operate full throttle against melanoma.

Ipilimumab is approved by the Food and Drug Administration for the treatment of metastatic melanoma. Nivolumab is an investigational agent that has been shown to have good antitumor activity in monotherapy.

"PD-1 and CTLA-4 both, as you\'ve heard before, are nonredundant checkpoints in T-cell differentiation and function, and there are several animal models that show synergy by combining these two agents," Dr. Sznol said in an oral abstract session.

As single agents, ipilimumab is associated with a 2-year overall survival rate of 24%, and nivolumab with a 2-year OS of 43%.

The investigators reported at ASCO 2013 and in the New England Journal of Medicine that the combined agents were associated with a 1-year OS of 82%.

Complex protocol

In the head-spinningly complex phase I dose-escalation study, patients with unresectable stage III or IV malignant melanoma were assigned to one of eight different dosing cohorts, looking at doses of nivolumab ranging from 0.3 to 10 mg/kg delivered in a 60 or 90 minute infusion every 2 or 3 weeks for up to 21 weeks, and to ipilimumab at doses ranging from 3 to 10 mg/kg delivered in 60- to 90-minute infusions every 3 weeks for 9 to 21 weeks of induction, followed by 84 to 96 weeks of maintenance therapy.

For the current report, Dr. Sznol and his colleagues looked at follow-up of 53 patients in dosing cohorts 1-3, all of whom received the drugs concurrently every 3 weeks for four doses, followed by nivolumab every 3 weeks for four doses, and then the combined agents every 12 weeks for eight doses. They also reported on a new, eighth cohort of 41 patients who received both drugs on the same induction schedule, followed by maintenance with nivolumab 3 mg/kg alone every 2 weeks until disease progression. This dosing schedule is being evaluated in phase II/III trials.

The overall response rate (ORR) for cohorts 1-3 was 42%, with 17% of patients having a complete response according to RECIST (Response Evaluation Criteria in Solid Tumors). In cohort 8, 40 of the 41 patients enrolled were evaluable for response, with an ORR of 43, and a 10% complete response rate (CRRs), although two of the CRRs were unconfirmed.

80% tumor shrinkage

In cohorts 1-3, 42% of patients had a reduction in tumor size of more than 80%, and many of these patients had complete or near-complete responses, Dr. Sznol said. Tumor shrinkage appeared similar in cohort 8, as shown on a waterfall plot, but Dr. Sznol did not report specifics about tumor dimensions in this group.

The median duration of responses in all four cohorts discussed has not been reached.

Grade 3 or 4 toxicities occurred in 62% of patients, with gastrointestinal side effects and elevated liver function tests occurring in 14% each, and increases in serum lipase in 15% and amylase in 6%. No new safety signals have emerged over 22 months of follow-up of patients in the initial cohorts, Dr. Sznol noted.

Dr. Jeffrey Weber of the Moffit Cancer Center in Tampa, Fla., the invited discussant, who has treated patients using the drugs in combination, commented that "Yes, you do see a large rate of patients with asymptomatic liver-function abnormalities that get better, and then you can retreat them."

Grade 3 elevated lipase or amylase may not require treatment, and grade 4 events may resolve with treatment interruption. Much of the toxicity occurs early with the concurrent regimen, and lessens during maintenance with nivolumab alone, he added.

Of the 94 patients in cohorts 1-3 and 8, 22 (23%) discontinued therapy due to treatment-related adverse events. One patient died from multiorgan failure associated with treatment-induced colitis; this patient was in cohort 8.

The study is supported by Bristol-Myers Squibb, Medarex, and Ono Pharma USA. Dr. Sznol disclosed consultant/advisory relationships with Bristol-Myers Squibb and several other companies. Dr. Weber disclosed consulting/advising, and received honoraria and research funding from Bristol-Myers Squibb and other companies. Dr. O’Day has received grants for research support from Bristol-Myers Squibb and Medarex, and he has served on the speakers bureau for Bristol-Myers Squibb.

CHICAGO – The investigational targeted agent pembrolizumab induced durable treatment responses in a high percentage of patients with advanced metastatic melanoma, in a phase I study.

Of 411 patients, 1-year overall survival was 69%, and 88% of patients who had a treatment response continued to have a response at 1 year, reported Dr. Antoni Ribas, professor of medicine at the University of California, Los Angeles, at a media briefing and in an oral abstract session at the annual meeting of the American Society for Clinical Oncology.

Neil Osterweil/ Frontline Medical News

"We used to say that melanoma had a median survival of 6-9 months – that wasn’t that long ago. Then we said well, maybe it’s getting closer to 12 months. Here, we have not reached the median overall survival," Dr. Ribas said.

At 18 months of follow-up, overall survival is 62%, and seems to be plateauing, but longer follow-up will be required to see how long the survival benefit can be maintained, he said.

"The remarkable thing is that almost 90% of these patients are having durable responses with a toxicity profile that is almost unheard of in metastatic cancer," commented Dr. Steven O’Day of the Beverly Hills (Calif.) Cancer Center, who moderated the briefing but was not involved in the study.

Grade 3 or 4 toxicities occurred in 12% of patients, making pembrolizumab "one of the most benign therapies that I have ever used in my clinic," he said.

New name, same PD-1 antibody

Pembrolizumab, formerly known as lambrolizumab or MK-3475, is a humanized monoclonal antibody targeted against the PD-1 immune system checkpoint. By binding to and inhibiting what Dr. Ribas called the "do not kill me" signal, the antibody allows the immune system to recognize and mount a more potent T-cell–mediated defense against melanoma.

The Food and Drug Administration previously granted permbrolizumab a breakthrough therapy designation, and in May 2014 gave it a priority review designation under the agency’s accelerated approval program.

At the 2013 ASCO annual meeting, Dr. Ribas and colleagues reported a 41% overall response rate (ORR) in the first 135 patients with metastatic melanoma treated with the antibody in the phase I study KEYNOTE 001.

The data he presented at this year’s ASCO meeting on the melanoma expansion cohort from that trial support the earlier findings from the study, showing an overall ORR of 34%, with responses seen in 44% of treatment-naive patients, 28% of those who had previously been treated with a different checkpoint inhibitor, ipilimumab (Yervoy), and 40% in patients who had received prior therapies other than ipilimumab.

The current study is an analysis of pooled data on 411 patients, 221 of whom had disease progression on ipilimumab and 190 of whom had never received ipilimumab. All patients had melanoma metastatic to the lungs or other organs.

Neil Osterweil/ Frontline Medical News

The patients received pembrolizumab in one of three dosing schedules: 10 mg/kg every 2 weeks (57 patients) or every 3 weeks (192), or 2 mg/kg every 3 weeks (162).

As noted, the overall survival rate at 1 year was 69% (74% for ipilimumab-naive patients and 65% for ipilimumab-treated patients), with the median overall survival not yet reached.

Dr. O’Day said it was encouraging that prior exposure to ipilimumab did not appear to dramatically decrease the benefit from pembrolizumab.

"This is critical to us understanding whether to combine or sequence these drugs, because there does not seem to be a lot of cross-resistance between ipilimumab and PD-1 [inhibition]," he said.

The most common adverse event of any grade was fatigue, occurring in 36% of patients, but only 2% of patients had grade 3 or 4 fatigue. Other common events were pruritus (24%), rash (20%), diarrhea (16%), arthralgia (16%), nausea (12%), and vitiligo (11%). The overall rate of any adverse events was 83%, but as noted before, only 12% of patients had a grade 3 or 4 adverse event. These events were manageable across all doses and in both ipilmumab-naive and experienced patients.

Pembrolizumab is currently being investigated in international, randomized controlled clinical trials, Dr. Ribas noted.

The study was supported by Merck. Dr. Ribas disclosed serving as a consultant/adviser to the company. Dr. O’Day reported having no relevant disclosures.

CHICAGO – The investigational targeted agent pembrolizumab induced durable treatment responses in a high percentage of patients with advanced metastatic melanoma, in a phase I study.

Of 411 patients, 1-year overall survival was 69%, and 88% of patients who had a treatment response continued to have a response at 1 year, reported Dr. Antoni Ribas, professor of medicine at the University of California, Los Angeles, at a media briefing and in an oral abstract session at the annual meeting of the American Society for Clinical Oncology.

Neil Osterweil/ Frontline Medical News

"We used to say that melanoma had a median survival of 6-9 months – that wasn’t that long ago. Then we said well, maybe it’s getting closer to 12 months. Here, we have not reached the median overall survival," Dr. Ribas said.

At 18 months of follow-up, overall survival is 62%, and seems to be plateauing, but longer follow-up will be required to see how long the survival benefit can be maintained, he said.

"The remarkable thing is that almost 90% of these patients are having durable responses with a toxicity profile that is almost unheard of in metastatic cancer," commented Dr. Steven O’Day of the Beverly Hills (Calif.) Cancer Center, who moderated the briefing but was not involved in the study.

Grade 3 or 4 toxicities occurred in 12% of patients, making pembrolizumab "one of the most benign therapies that I have ever used in my clinic," he said.

New name, same PD-1 antibody

Pembrolizumab, formerly known as lambrolizumab or MK-3475, is a humanized monoclonal antibody targeted against the PD-1 immune system checkpoint. By binding to and inhibiting what Dr. Ribas called the "do not kill me" signal, the antibody allows the immune system to recognize and mount a more potent T-cell–mediated defense against melanoma.

The Food and Drug Administration previously granted permbrolizumab a breakthrough therapy designation, and in May 2014 gave it a priority review designation under the agency’s accelerated approval program.

At the 2013 ASCO annual meeting, Dr. Ribas and colleagues reported a 41% overall response rate (ORR) in the first 135 patients with metastatic melanoma treated with the antibody in the phase I study KEYNOTE 001.

The data he presented at this year’s ASCO meeting on the melanoma expansion cohort from that trial support the earlier findings from the study, showing an overall ORR of 34%, with responses seen in 44% of treatment-naive patients, 28% of those who had previously been treated with a different checkpoint inhibitor, ipilimumab (Yervoy), and 40% in patients who had received prior therapies other than ipilimumab.

The current study is an analysis of pooled data on 411 patients, 221 of whom had disease progression on ipilimumab and 190 of whom had never received ipilimumab. All patients had melanoma metastatic to the lungs or other organs.

Neil Osterweil/ Frontline Medical News

The patients received pembrolizumab in one of three dosing schedules: 10 mg/kg every 2 weeks (57 patients) or every 3 weeks (192), or 2 mg/kg every 3 weeks (162).

As noted, the overall survival rate at 1 year was 69% (74% for ipilimumab-naive patients and 65% for ipilimumab-treated patients), with the median overall survival not yet reached.

Dr. O’Day said it was encouraging that prior exposure to ipilimumab did not appear to dramatically decrease the benefit from pembrolizumab.

"This is critical to us understanding whether to combine or sequence these drugs, because there does not seem to be a lot of cross-resistance between ipilimumab and PD-1 [inhibition]," he said.

The most common adverse event of any grade was fatigue, occurring in 36% of patients, but only 2% of patients had grade 3 or 4 fatigue. Other common events were pruritus (24%), rash (20%), diarrhea (16%), arthralgia (16%), nausea (12%), and vitiligo (11%). The overall rate of any adverse events was 83%, but as noted before, only 12% of patients had a grade 3 or 4 adverse event. These events were manageable across all doses and in both ipilmumab-naive and experienced patients.

Pembrolizumab is currently being investigated in international, randomized controlled clinical trials, Dr. Ribas noted.

The study was supported by Merck. Dr. Ribas disclosed serving as a consultant/adviser to the company. Dr. O’Day reported having no relevant disclosures.

CHICAGO – The investigational targeted agent pembrolizumab induced durable treatment responses in a high percentage of patients with advanced metastatic melanoma, in a phase I study.

Of 411 patients, 1-year overall survival was 69%, and 88% of patients who had a treatment response continued to have a response at 1 year, reported Dr. Antoni Ribas, professor of medicine at the University of California, Los Angeles, at a media briefing and in an oral abstract session at the annual meeting of the American Society for Clinical Oncology.

Neil Osterweil/ Frontline Medical News

"We used to say that melanoma had a median survival of 6-9 months – that wasn’t that long ago. Then we said well, maybe it’s getting closer to 12 months. Here, we have not reached the median overall survival," Dr. Ribas said.

At 18 months of follow-up, overall survival is 62%, and seems to be plateauing, but longer follow-up will be required to see how long the survival benefit can be maintained, he said.

"The remarkable thing is that almost 90% of these patients are having durable responses with a toxicity profile that is almost unheard of in metastatic cancer," commented Dr. Steven O’Day of the Beverly Hills (Calif.) Cancer Center, who moderated the briefing but was not involved in the study.

Grade 3 or 4 toxicities occurred in 12% of patients, making pembrolizumab "one of the most benign therapies that I have ever used in my clinic," he said.

New name, same PD-1 antibody

Pembrolizumab, formerly known as lambrolizumab or MK-3475, is a humanized monoclonal antibody targeted against the PD-1 immune system checkpoint. By binding to and inhibiting what Dr. Ribas called the "do not kill me" signal, the antibody allows the immune system to recognize and mount a more potent T-cell–mediated defense against melanoma.

The Food and Drug Administration previously granted permbrolizumab a breakthrough therapy designation, and in May 2014 gave it a priority review designation under the agency’s accelerated approval program.

At the 2013 ASCO annual meeting, Dr. Ribas and colleagues reported a 41% overall response rate (ORR) in the first 135 patients with metastatic melanoma treated with the antibody in the phase I study KEYNOTE 001.

The data he presented at this year’s ASCO meeting on the melanoma expansion cohort from that trial support the earlier findings from the study, showing an overall ORR of 34%, with responses seen in 44% of treatment-naive patients, 28% of those who had previously been treated with a different checkpoint inhibitor, ipilimumab (Yervoy), and 40% in patients who had received prior therapies other than ipilimumab.

The current study is an analysis of pooled data on 411 patients, 221 of whom had disease progression on ipilimumab and 190 of whom had never received ipilimumab. All patients had melanoma metastatic to the lungs or other organs.

Neil Osterweil/ Frontline Medical News

The patients received pembrolizumab in one of three dosing schedules: 10 mg/kg every 2 weeks (57 patients) or every 3 weeks (192), or 2 mg/kg every 3 weeks (162).

As noted, the overall survival rate at 1 year was 69% (74% for ipilimumab-naive patients and 65% for ipilimumab-treated patients), with the median overall survival not yet reached.

Dr. O’Day said it was encouraging that prior exposure to ipilimumab did not appear to dramatically decrease the benefit from pembrolizumab.

"This is critical to us understanding whether to combine or sequence these drugs, because there does not seem to be a lot of cross-resistance between ipilimumab and PD-1 [inhibition]," he said.

The most common adverse event of any grade was fatigue, occurring in 36% of patients, but only 2% of patients had grade 3 or 4 fatigue. Other common events were pruritus (24%), rash (20%), diarrhea (16%), arthralgia (16%), nausea (12%), and vitiligo (11%). The overall rate of any adverse events was 83%, but as noted before, only 12% of patients had a grade 3 or 4 adverse event. These events were manageable across all doses and in both ipilmumab-naive and experienced patients.

Pembrolizumab is currently being investigated in international, randomized controlled clinical trials, Dr. Ribas noted.

The study was supported by Merck. Dr. Ribas disclosed serving as a consultant/adviser to the company. Dr. O’Day reported having no relevant disclosures.

The Food and Drug Administration is requiring all tanning beds to carry a "black box" warning that the devices should not be used by children under age 18 years.

The labeling doesn’t carry any penalties for allowing teens to use tanning beds, but FDA officials said it sends a signal about their safety to the public.

"It reflects a very strong statement by FDA that we do not believe [tanning beds] should be used in individuals under the age of 18 because of the evidence that cumulative exposure to UV radiation is harmful to individuals and increases the likelihood of skin cancers, including melanoma," said Nancy Stade, deputy director for policy at the FDA’s Center for Devices and Radiological Health.

©Vidmantas Goldbergas/iStockphoto.com

Agency officials did not rule out taking further actions to restrict tanning bed use in the future.

In a final order released on May 29, the FDA reclassified sunlamp products and ultraviolet (UV) lamps intended for use in sunlamp products from class I (low-risk) to class II (moderate-risk) devices. The regulatory change allows the agency to require tanning bed manufacturers to submit a premarket notification, also called a 510(k) submission, prior to marketing the devices. The premarket notification process requires manufacturers to show that their products meet certain performance testing requirements.

The new classification also allows FDA to require more stringent labeling of tanning beds.

The FDA is ordering all tanning beds to prominently display a black box warning on the device that states "Attention: This sunlamp product should not be used on persons under the age of 18 years."

Marketing materials including websites, brochures, and user instructions must carry four additional warning statements under the new FDA order. The warning statements include:

• Contraindication: This product is contraindicated for use on persons under the age of 18 years.

• Contraindication: This product must not be used if skin lesions or open wounds are present.

• Warning: This product should not be used on individuals who have had skin cancer or have a family history of skin cancer.

• Warning: Persons repeatedly exposed to UV radiation should be regularly evaluated for skin cancer.

In strengthening the warning label for tanning beds, the FDA cited statistics from the American Academy of Dermatology that individuals who have been exposed to UV radiation from indoor tanning experience a 59% increase in their risk of melanoma. The risk increases each time an individual uses a sunlamp product, according to the AAD.

The new rules take effect 90 days after their official publication on June 2. For new tanning devices, manufacturers must begin submitting 510(k) notifications after the effective date of the regulation. For devices that are already on the market, manufacturers have 450 days to submit their 510(k) notification and comply with the new labeling requirements.

Physician groups, including the AAD, praised the increased regulation of tanning beds.

"Restricting teens’ access to indoor tanning is critical to preventing skin cancer," Dr. Brett M. Coldiron, president of the AAD, said in a statement. "As medical doctors who diagnose and treat skin cancer, dermatologists are committed to reducing its incidence and saving lives. Therefore, we will continue to communicate to the FDA the need for stricter regulations on the use and sale of indoor tanning devices for minors under the age of 18."

[email protected]

On Twitter @maryellenny

The Food and Drug Administration is requiring all tanning beds to carry a "black box" warning that the devices should not be used by children under age 18 years.

The labeling doesn’t carry any penalties for allowing teens to use tanning beds, but FDA officials said it sends a signal about their safety to the public.

"It reflects a very strong statement by FDA that we do not believe [tanning beds] should be used in individuals under the age of 18 because of the evidence that cumulative exposure to UV radiation is harmful to individuals and increases the likelihood of skin cancers, including melanoma," said Nancy Stade, deputy director for policy at the FDA’s Center for Devices and Radiological Health.

©Vidmantas Goldbergas/iStockphoto.com

Agency officials did not rule out taking further actions to restrict tanning bed use in the future.

In a final order released on May 29, the FDA reclassified sunlamp products and ultraviolet (UV) lamps intended for use in sunlamp products from class I (low-risk) to class II (moderate-risk) devices. The regulatory change allows the agency to require tanning bed manufacturers to submit a premarket notification, also called a 510(k) submission, prior to marketing the devices. The premarket notification process requires manufacturers to show that their products meet certain performance testing requirements.

The new classification also allows FDA to require more stringent labeling of tanning beds.

The FDA is ordering all tanning beds to prominently display a black box warning on the device that states "Attention: This sunlamp product should not be used on persons under the age of 18 years."

Marketing materials including websites, brochures, and user instructions must carry four additional warning statements under the new FDA order. The warning statements include:

• Contraindication: This product is contraindicated for use on persons under the age of 18 years.

• Contraindication: This product must not be used if skin lesions or open wounds are present.

• Warning: This product should not be used on individuals who have had skin cancer or have a family history of skin cancer.

• Warning: Persons repeatedly exposed to UV radiation should be regularly evaluated for skin cancer.

In strengthening the warning label for tanning beds, the FDA cited statistics from the American Academy of Dermatology that individuals who have been exposed to UV radiation from indoor tanning experience a 59% increase in their risk of melanoma. The risk increases each time an individual uses a sunlamp product, according to the AAD.

The new rules take effect 90 days after their official publication on June 2. For new tanning devices, manufacturers must begin submitting 510(k) notifications after the effective date of the regulation. For devices that are already on the market, manufacturers have 450 days to submit their 510(k) notification and comply with the new labeling requirements.

Physician groups, including the AAD, praised the increased regulation of tanning beds.

"Restricting teens’ access to indoor tanning is critical to preventing skin cancer," Dr. Brett M. Coldiron, president of the AAD, said in a statement. "As medical doctors who diagnose and treat skin cancer, dermatologists are committed to reducing its incidence and saving lives. Therefore, we will continue to communicate to the FDA the need for stricter regulations on the use and sale of indoor tanning devices for minors under the age of 18."

[email protected]

On Twitter @maryellenny

The Food and Drug Administration is requiring all tanning beds to carry a "black box" warning that the devices should not be used by children under age 18 years.

The labeling doesn’t carry any penalties for allowing teens to use tanning beds, but FDA officials said it sends a signal about their safety to the public.

"It reflects a very strong statement by FDA that we do not believe [tanning beds] should be used in individuals under the age of 18 because of the evidence that cumulative exposure to UV radiation is harmful to individuals and increases the likelihood of skin cancers, including melanoma," said Nancy Stade, deputy director for policy at the FDA’s Center for Devices and Radiological Health.

©Vidmantas Goldbergas/iStockphoto.com

Agency officials did not rule out taking further actions to restrict tanning bed use in the future.

In a final order released on May 29, the FDA reclassified sunlamp products and ultraviolet (UV) lamps intended for use in sunlamp products from class I (low-risk) to class II (moderate-risk) devices. The regulatory change allows the agency to require tanning bed manufacturers to submit a premarket notification, also called a 510(k) submission, prior to marketing the devices. The premarket notification process requires manufacturers to show that their products meet certain performance testing requirements.

The new classification also allows FDA to require more stringent labeling of tanning beds.

The FDA is ordering all tanning beds to prominently display a black box warning on the device that states "Attention: This sunlamp product should not be used on persons under the age of 18 years."

Marketing materials including websites, brochures, and user instructions must carry four additional warning statements under the new FDA order. The warning statements include:

• Contraindication: This product is contraindicated for use on persons under the age of 18 years.

• Contraindication: This product must not be used if skin lesions or open wounds are present.

• Warning: This product should not be used on individuals who have had skin cancer or have a family history of skin cancer.

• Warning: Persons repeatedly exposed to UV radiation should be regularly evaluated for skin cancer.

In strengthening the warning label for tanning beds, the FDA cited statistics from the American Academy of Dermatology that individuals who have been exposed to UV radiation from indoor tanning experience a 59% increase in their risk of melanoma. The risk increases each time an individual uses a sunlamp product, according to the AAD.

The new rules take effect 90 days after their official publication on June 2. For new tanning devices, manufacturers must begin submitting 510(k) notifications after the effective date of the regulation. For devices that are already on the market, manufacturers have 450 days to submit their 510(k) notification and comply with the new labeling requirements.

Physician groups, including the AAD, praised the increased regulation of tanning beds.

"Restricting teens’ access to indoor tanning is critical to preventing skin cancer," Dr. Brett M. Coldiron, president of the AAD, said in a statement. "As medical doctors who diagnose and treat skin cancer, dermatologists are committed to reducing its incidence and saving lives. Therefore, we will continue to communicate to the FDA the need for stricter regulations on the use and sale of indoor tanning devices for minors under the age of 18."

[email protected]

On Twitter @maryellenny

Melanoma risk increased by 80% among women who had five or more severe sunburns as teenagers, based on a review of data from more than 100,000 white women.

The findings were published online May 29 in Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.

©garth11/thinkstockphotos.com

"We investigated the relationship between a number of potential risk factors, including chronic sun exposure over long durations in adulthood and sun exposure in early life, and risk of different types of skin cancer," wrote Dr. Shaowei Wu of Brigham and Women’s Hospital, Boston, and colleagues.

Diagnoses of 6,955 basal cell carcinomas (BCCs), 880 squamous cell carcinomas (SCCs), and 779 melanomas were identified during 2.05 million person-years of follow-up. The relative risk of skin cancer was 68% higher for both BCC and SCC, and 80% higher for melanoma in women who reported five or more blistering sunburns between ages 15 and 25 years, compared with those who reported no such sunburns (Cancer Epidemiol. Biomarkers Prev. 2014;23:1080-9).

The study included 101,916 nurses participating in the Nurses’ Health Study II. The women enrolled between the ages of 25 and 42 years, and were followed for 20 years between 1989 and 2009. The eligible participants had no baseline history of any cancer and were diagnosed with incident BCC, SCC, or melanoma between baseline and the last follow-up.

Cumulative ultraviolet radiation exposure in adulthood, measured over long durations using a composite estimate called UV flux, also was associated with an increased risk of BCC and SCC, but not with melanoma. This suggests that "melanoma may have a more complicated relationship with sun exposure than SCC and BCC," the researchers said.

The study was limited by the approximate estimates of UV radiation exposure, incomplete information about personal behaviors such as sunscreen use, and the fact that BCC cases were not independently validated as SCC and melanoma. However, the findings "support heterogenous associations between sun exposure, other potential risk factors, and risk of different types of skin cancer, and thus may have potential implications for the prevention of skin cancers," the researchers noted.

Also, "our participants consisted entirely of white women, and thus the generalizability of the results to men and other ethnicities may be limited," they said.

The study was supported by the department of dermatology at Brigham and Women’s Hospital, and by a grant from the National Institutes of Health. Corresponding author Dr. Abrar A. Qureshi has served as a consultant and/or advisory board member for multiple pharmaceutical companies. The other authors had no financial conflicts to disclose.

[email protected]

Melanoma risk increased by 80% among women who had five or more severe sunburns as teenagers, based on a review of data from more than 100,000 white women.

The findings were published online May 29 in Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.

©garth11/thinkstockphotos.com

"We investigated the relationship between a number of potential risk factors, including chronic sun exposure over long durations in adulthood and sun exposure in early life, and risk of different types of skin cancer," wrote Dr. Shaowei Wu of Brigham and Women’s Hospital, Boston, and colleagues.

Diagnoses of 6,955 basal cell carcinomas (BCCs), 880 squamous cell carcinomas (SCCs), and 779 melanomas were identified during 2.05 million person-years of follow-up. The relative risk of skin cancer was 68% higher for both BCC and SCC, and 80% higher for melanoma in women who reported five or more blistering sunburns between ages 15 and 25 years, compared with those who reported no such sunburns (Cancer Epidemiol. Biomarkers Prev. 2014;23:1080-9).

The study included 101,916 nurses participating in the Nurses’ Health Study II. The women enrolled between the ages of 25 and 42 years, and were followed for 20 years between 1989 and 2009. The eligible participants had no baseline history of any cancer and were diagnosed with incident BCC, SCC, or melanoma between baseline and the last follow-up.

Cumulative ultraviolet radiation exposure in adulthood, measured over long durations using a composite estimate called UV flux, also was associated with an increased risk of BCC and SCC, but not with melanoma. This suggests that "melanoma may have a more complicated relationship with sun exposure than SCC and BCC," the researchers said.

The study was limited by the approximate estimates of UV radiation exposure, incomplete information about personal behaviors such as sunscreen use, and the fact that BCC cases were not independently validated as SCC and melanoma. However, the findings "support heterogenous associations between sun exposure, other potential risk factors, and risk of different types of skin cancer, and thus may have potential implications for the prevention of skin cancers," the researchers noted.

Also, "our participants consisted entirely of white women, and thus the generalizability of the results to men and other ethnicities may be limited," they said.

The study was supported by the department of dermatology at Brigham and Women’s Hospital, and by a grant from the National Institutes of Health. Corresponding author Dr. Abrar A. Qureshi has served as a consultant and/or advisory board member for multiple pharmaceutical companies. The other authors had no financial conflicts to disclose.

[email protected]

Melanoma risk increased by 80% among women who had five or more severe sunburns as teenagers, based on a review of data from more than 100,000 white women.

The findings were published online May 29 in Cancer Epidemiology, Biomarkers and Prevention, a journal of the American Association for Cancer Research.

©garth11/thinkstockphotos.com

"We investigated the relationship between a number of potential risk factors, including chronic sun exposure over long durations in adulthood and sun exposure in early life, and risk of different types of skin cancer," wrote Dr. Shaowei Wu of Brigham and Women’s Hospital, Boston, and colleagues.

Diagnoses of 6,955 basal cell carcinomas (BCCs), 880 squamous cell carcinomas (SCCs), and 779 melanomas were identified during 2.05 million person-years of follow-up. The relative risk of skin cancer was 68% higher for both BCC and SCC, and 80% higher for melanoma in women who reported five or more blistering sunburns between ages 15 and 25 years, compared with those who reported no such sunburns (Cancer Epidemiol. Biomarkers Prev. 2014;23:1080-9).

The study included 101,916 nurses participating in the Nurses’ Health Study II. The women enrolled between the ages of 25 and 42 years, and were followed for 20 years between 1989 and 2009. The eligible participants had no baseline history of any cancer and were diagnosed with incident BCC, SCC, or melanoma between baseline and the last follow-up.

Cumulative ultraviolet radiation exposure in adulthood, measured over long durations using a composite estimate called UV flux, also was associated with an increased risk of BCC and SCC, but not with melanoma. This suggests that "melanoma may have a more complicated relationship with sun exposure than SCC and BCC," the researchers said.

The study was limited by the approximate estimates of UV radiation exposure, incomplete information about personal behaviors such as sunscreen use, and the fact that BCC cases were not independently validated as SCC and melanoma. However, the findings "support heterogenous associations between sun exposure, other potential risk factors, and risk of different types of skin cancer, and thus may have potential implications for the prevention of skin cancers," the researchers noted.

Also, "our participants consisted entirely of white women, and thus the generalizability of the results to men and other ethnicities may be limited," they said.

The study was supported by the department of dermatology at Brigham and Women’s Hospital, and by a grant from the National Institutes of Health. Corresponding author Dr. Abrar A. Qureshi has served as a consultant and/or advisory board member for multiple pharmaceutical companies. The other authors had no financial conflicts to disclose.

[email protected]

A diagnosis of a chronic and/or serious medical condition can be a traumatic experience. Patients may experience not only intrusive thoughts but also avoidance behaviors. The affected individuals can express these trauma-associated symptoms as depression, fatigue, and sleep disturbance.

Milbury et al (J Clin Oncol. 2014;32:663-670) included 277 patients who had been diagnosed with renal cell carcinoma in a study to evaluate if writing about their deepest thoughts and feelings regarding their cancer (expressive writing) offered a quality-of-life benefit compared to writing about neutral topics (neutral writing). They found that expressive writing not only reduced the patients’ cancer-related symptoms but also improved their physical functioning.

What’s the issue?

Many of the conditions that affect dermatology patients are chronic, serious, or both. For example, psoriasis is a chronic skin condition with the potential for serious associated rheumatologic or metabolic sequelae. In addition, skin malignancies (eg, basal cell carcinoma, squamous cell carcinoma, malignant melanoma) and cutaneous lymphoma (eg, mycosis fungoides) are conditions that require chronic surveillance and possibly may have serious consequences.

Expressive writing for dermatology patients might result in remarkable improvement in emotional and physical health. Perhaps dermatologists should recommend this intervention for their patients.

We want to know your views! Tell us what you think.

A diagnosis of a chronic and/or serious medical condition can be a traumatic experience. Patients may experience not only intrusive thoughts but also avoidance behaviors. The affected individuals can express these trauma-associated symptoms as depression, fatigue, and sleep disturbance.

Milbury et al (J Clin Oncol. 2014;32:663-670) included 277 patients who had been diagnosed with renal cell carcinoma in a study to evaluate if writing about their deepest thoughts and feelings regarding their cancer (expressive writing) offered a quality-of-life benefit compared to writing about neutral topics (neutral writing). They found that expressive writing not only reduced the patients’ cancer-related symptoms but also improved their physical functioning.

What’s the issue?

Many of the conditions that affect dermatology patients are chronic, serious, or both. For example, psoriasis is a chronic skin condition with the potential for serious associated rheumatologic or metabolic sequelae. In addition, skin malignancies (eg, basal cell carcinoma, squamous cell carcinoma, malignant melanoma) and cutaneous lymphoma (eg, mycosis fungoides) are conditions that require chronic surveillance and possibly may have serious consequences.

Expressive writing for dermatology patients might result in remarkable improvement in emotional and physical health. Perhaps dermatologists should recommend this intervention for their patients.

We want to know your views! Tell us what you think.

A diagnosis of a chronic and/or serious medical condition can be a traumatic experience. Patients may experience not only intrusive thoughts but also avoidance behaviors. The affected individuals can express these trauma-associated symptoms as depression, fatigue, and sleep disturbance.

Milbury et al (J Clin Oncol. 2014;32:663-670) included 277 patients who had been diagnosed with renal cell carcinoma in a study to evaluate if writing about their deepest thoughts and feelings regarding their cancer (expressive writing) offered a quality-of-life benefit compared to writing about neutral topics (neutral writing). They found that expressive writing not only reduced the patients’ cancer-related symptoms but also improved their physical functioning.

What’s the issue?

Many of the conditions that affect dermatology patients are chronic, serious, or both. For example, psoriasis is a chronic skin condition with the potential for serious associated rheumatologic or metabolic sequelae. In addition, skin malignancies (eg, basal cell carcinoma, squamous cell carcinoma, malignant melanoma) and cutaneous lymphoma (eg, mycosis fungoides) are conditions that require chronic surveillance and possibly may have serious consequences.

Expressive writing for dermatology patients might result in remarkable improvement in emotional and physical health. Perhaps dermatologists should recommend this intervention for their patients.

We want to know your views! Tell us what you think.

1. Abstract LBA 9000, Antoni Ribas et al.

Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL).

http://abstracts.asco.org/144/AbstView_144_133842.html

2. Abstract LBA 9008, Alexander M. Eggermont et al. Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.

http://abstracts.asco.org/144/AbstView_144_130118.html

3. Abstract 9011, Georgina V. Long et al.

COMBI-d: A randomized, double-blinded, phase III study comparing the combination of dabrafenib and trametinib to dabrafenib and trametinib placebo as first-line therapy in patients (pts) with unresectable or metastatic BRAF^V600E/K mutation-positive cutaneous melanoma.

http://abstracts.asco.org/144/AbstView_144_128598.html

4. Abstract 9008a, Howard L. Kaufman et al.

Primary overall survival (OS) from OPTiM, a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

http://abstracts.asco.org/144/AbstView_144_133898.html

5. Abstract 9010, Keith Flaherty et al.

Updated overall survival (OS) for BRF113220, a phase 1-2 study of dabrafenib (D) alone versus combined dabrafenib and trametinib (D+T) in pts with BRAF V600 mutation-positive (+) metastatic melanoma (MM).

http://abstracts.asco.org/144/AbstView_144_134903.html

Dr. Jeffrey A. Sosman is professor of medicine and Ingram Professor for Cancer Research, Vanderbilt University Medical Center, Nashville, Tenn.

1. Abstract LBA 9000, Antoni Ribas et al.

Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL).

http://abstracts.asco.org/144/AbstView_144_133842.html

2. Abstract LBA 9008, Alexander M. Eggermont et al. Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.

http://abstracts.asco.org/144/AbstView_144_130118.html

3. Abstract 9011, Georgina V. Long et al.

COMBI-d: A randomized, double-blinded, phase III study comparing the combination of dabrafenib and trametinib to dabrafenib and trametinib placebo as first-line therapy in patients (pts) with unresectable or metastatic BRAF^V600E/K mutation-positive cutaneous melanoma.

http://abstracts.asco.org/144/AbstView_144_128598.html

4. Abstract 9008a, Howard L. Kaufman et al.

Primary overall survival (OS) from OPTiM, a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

http://abstracts.asco.org/144/AbstView_144_133898.html

5. Abstract 9010, Keith Flaherty et al.

Updated overall survival (OS) for BRF113220, a phase 1-2 study of dabrafenib (D) alone versus combined dabrafenib and trametinib (D+T) in pts with BRAF V600 mutation-positive (+) metastatic melanoma (MM).

http://abstracts.asco.org/144/AbstView_144_134903.html

Dr. Jeffrey A. Sosman is professor of medicine and Ingram Professor for Cancer Research, Vanderbilt University Medical Center, Nashville, Tenn.

1. Abstract LBA 9000, Antoni Ribas et al.

Efficacy and safety of the anti-PD-1 monoclonal antibody MK-3475 in 411 patients (pts) with melanoma (MEL).

http://abstracts.asco.org/144/AbstView_144_133842.html

2. Abstract LBA 9008, Alexander M. Eggermont et al. Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.

http://abstracts.asco.org/144/AbstView_144_130118.html

3. Abstract 9011, Georgina V. Long et al.

COMBI-d: A randomized, double-blinded, phase III study comparing the combination of dabrafenib and trametinib to dabrafenib and trametinib placebo as first-line therapy in patients (pts) with unresectable or metastatic BRAF^V600E/K mutation-positive cutaneous melanoma.

http://abstracts.asco.org/144/AbstView_144_128598.html

4. Abstract 9008a, Howard L. Kaufman et al.

Primary overall survival (OS) from OPTiM, a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

http://abstracts.asco.org/144/AbstView_144_133898.html

5. Abstract 9010, Keith Flaherty et al.

Updated overall survival (OS) for BRF113220, a phase 1-2 study of dabrafenib (D) alone versus combined dabrafenib and trametinib (D+T) in pts with BRAF V600 mutation-positive (+) metastatic melanoma (MM).

http://abstracts.asco.org/144/AbstView_144_134903.html

Dr. Jeffrey A. Sosman is professor of medicine and Ingram Professor for Cancer Research, Vanderbilt University Medical Center, Nashville, Tenn.

DENVER – As the nanotechnology field evolves, there are at least three reasons a clinician might prefer to use nanoparticles over conventional drugs, according to Dr. Jack L. Arbiser. The first is to minimize the effects of a systemic drug.

"What if steroids could be directed to the site of the pathologic lesion but not cause side effects such as glucose intolerance, bone fractures, or gastric ulcers?" he asked during a session on nanotechnology at the annual meeting of the American Academy of Dermatology. "What if propranolol could be given to patients with hemangiomas without having to worry about cardiac side effects?"

A second reason to turn to nanoparticles would be to use highly toxic substances in a safe way, continued Dr. Arbiser, a professor of dermatology at Emory University, Atlanta. "We already use Botox by injection, which is one of the most toxic substances known to man, but what if other highly toxic substances could be specifically delivered to cancers, infections, or inflammation?"

A third reason to use nanoparticles is that they may offer a way for compounds "that are not highly active be delivered to sites of disease in high enough concentration so that they have therapeutic activity and provide a high measure of safety," he said.

Dr. Arbiser discussed his nanotechnology experience as part of a research team developing a derivative of gentian violet for cancer treatment. He and his associates observed that gentian violet has potential antitumor activity through inhibition of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase. However, the researchers faced early challenges, because gentian violet is not patentable by itself, and, because it is hydrophilic, it may not pass through the blood-brain barrier.

"Our solution was to synthesize and patent a more lipophilic derivative of gentian violet called imipramine blue," Dr. Arbiser explained. "We packaged it in liposomes so it has a much longer half-life and is directed to tumors because liposomes preferentially localize to leaky blood vessels."

Imipramine blue can be given weekly and is efficacious against cancer tumors. Dr. Arbiser and his associates have demonstrated that systemic delivery of imipramine blue significantly inhibited migration of glioblastoma cells into the brain parenchyma (Sci. Transl. Med. 2012;4:127ra36).

"We also see this [inhibition of spread] in prostate, breast, and melanoma cells," he said. "So it seems to be hitting the same pathway in multiple different tumor types." Such an approach targets delivery of therapeutic and diagnostic imaging agents to the site of cancer and chronic inflammation/infection, potentially reducing side effects and increasing efficacy.

"My own personal bias is that we should start using metal-based nanotechnology for severe illnesses, such as cancers, allowing the effects of these materials to be studied in humans, before widespread introduction into cosmetics," he concluded.

Dr. Arbiser disclosed that he is the cofounder of companies ABBY Therapeutics and Accuitis.

[email protected]

DENVER – As the nanotechnology field evolves, there are at least three reasons a clinician might prefer to use nanoparticles over conventional drugs, according to Dr. Jack L. Arbiser. The first is to minimize the effects of a systemic drug.

"What if steroids could be directed to the site of the pathologic lesion but not cause side effects such as glucose intolerance, bone fractures, or gastric ulcers?" he asked during a session on nanotechnology at the annual meeting of the American Academy of Dermatology. "What if propranolol could be given to patients with hemangiomas without having to worry about cardiac side effects?"

A second reason to turn to nanoparticles would be to use highly toxic substances in a safe way, continued Dr. Arbiser, a professor of dermatology at Emory University, Atlanta. "We already use Botox by injection, which is one of the most toxic substances known to man, but what if other highly toxic substances could be specifically delivered to cancers, infections, or inflammation?"

A third reason to use nanoparticles is that they may offer a way for compounds "that are not highly active be delivered to sites of disease in high enough concentration so that they have therapeutic activity and provide a high measure of safety," he said.

Dr. Arbiser discussed his nanotechnology experience as part of a research team developing a derivative of gentian violet for cancer treatment. He and his associates observed that gentian violet has potential antitumor activity through inhibition of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase. However, the researchers faced early challenges, because gentian violet is not patentable by itself, and, because it is hydrophilic, it may not pass through the blood-brain barrier.

"Our solution was to synthesize and patent a more lipophilic derivative of gentian violet called imipramine blue," Dr. Arbiser explained. "We packaged it in liposomes so it has a much longer half-life and is directed to tumors because liposomes preferentially localize to leaky blood vessels."

Imipramine blue can be given weekly and is efficacious against cancer tumors. Dr. Arbiser and his associates have demonstrated that systemic delivery of imipramine blue significantly inhibited migration of glioblastoma cells into the brain parenchyma (Sci. Transl. Med. 2012;4:127ra36).

"We also see this [inhibition of spread] in prostate, breast, and melanoma cells," he said. "So it seems to be hitting the same pathway in multiple different tumor types." Such an approach targets delivery of therapeutic and diagnostic imaging agents to the site of cancer and chronic inflammation/infection, potentially reducing side effects and increasing efficacy.

"My own personal bias is that we should start using metal-based nanotechnology for severe illnesses, such as cancers, allowing the effects of these materials to be studied in humans, before widespread introduction into cosmetics," he concluded.

Dr. Arbiser disclosed that he is the cofounder of companies ABBY Therapeutics and Accuitis.

[email protected]

DENVER – As the nanotechnology field evolves, there are at least three reasons a clinician might prefer to use nanoparticles over conventional drugs, according to Dr. Jack L. Arbiser. The first is to minimize the effects of a systemic drug.

"What if steroids could be directed to the site of the pathologic lesion but not cause side effects such as glucose intolerance, bone fractures, or gastric ulcers?" he asked during a session on nanotechnology at the annual meeting of the American Academy of Dermatology. "What if propranolol could be given to patients with hemangiomas without having to worry about cardiac side effects?"

A second reason to turn to nanoparticles would be to use highly toxic substances in a safe way, continued Dr. Arbiser, a professor of dermatology at Emory University, Atlanta. "We already use Botox by injection, which is one of the most toxic substances known to man, but what if other highly toxic substances could be specifically delivered to cancers, infections, or inflammation?"

A third reason to use nanoparticles is that they may offer a way for compounds "that are not highly active be delivered to sites of disease in high enough concentration so that they have therapeutic activity and provide a high measure of safety," he said.

Dr. Arbiser discussed his nanotechnology experience as part of a research team developing a derivative of gentian violet for cancer treatment. He and his associates observed that gentian violet has potential antitumor activity through inhibition of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase. However, the researchers faced early challenges, because gentian violet is not patentable by itself, and, because it is hydrophilic, it may not pass through the blood-brain barrier.

"Our solution was to synthesize and patent a more lipophilic derivative of gentian violet called imipramine blue," Dr. Arbiser explained. "We packaged it in liposomes so it has a much longer half-life and is directed to tumors because liposomes preferentially localize to leaky blood vessels."

Imipramine blue can be given weekly and is efficacious against cancer tumors. Dr. Arbiser and his associates have demonstrated that systemic delivery of imipramine blue significantly inhibited migration of glioblastoma cells into the brain parenchyma (Sci. Transl. Med. 2012;4:127ra36).

"We also see this [inhibition of spread] in prostate, breast, and melanoma cells," he said. "So it seems to be hitting the same pathway in multiple different tumor types." Such an approach targets delivery of therapeutic and diagnostic imaging agents to the site of cancer and chronic inflammation/infection, potentially reducing side effects and increasing efficacy.

"My own personal bias is that we should start using metal-based nanotechnology for severe illnesses, such as cancers, allowing the effects of these materials to be studied in humans, before widespread introduction into cosmetics," he concluded.

Dr. Arbiser disclosed that he is the cofounder of companies ABBY Therapeutics and Accuitis.

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