Melanoma

PALM BEACH, ARUBA – Chemotherapy can trigger a host of skin presentations, the specific histologies of which may not be as recognizable to oncologists and hematologists as they would be to dermatologists and primary care physicians. Dr. Jean L. Bolognia, professor of dermatology and vice chair of clinical affairs at Yale University, New Haven, Conn., suggests that by using the all-encompassing clinical term "toxic erythema of chemotherapy," a common ground can be established between all members of a patient’s cancer treatment team, and better outcomes achieved.

In this podcast, Dr. Bolognia offers clinicians specifics for determining when a patient is experiencing a cutaneous reaction to chemotherapy or biologics vs. other skin diseases, and suggests ways to adjust treatment to lessen skin reactions. "It requires adjusting some of the misconceptions about drug eruptions," advises Dr. Bolognia. "This is a toxic reaction, not an allergic one." The distinction is important, according to Dr. Bolognia, especially if the patient is responding to their primary treatment; rather than stop a medication, the timing and dosage can be changed.

Among other tips, such as which drugs create certain drug eruptions, Dr. Bolognia reminds dermatologists and primary care clinicians including physician’s assistants that even a month after treatment, cutaneous reactions are possible.

[email protected]

On Twitter @whitneymcknight

PALM BEACH, ARUBA – Chemotherapy can trigger a host of skin presentations, the specific histologies of which may not be as recognizable to oncologists and hematologists as they would be to dermatologists and primary care physicians. Dr. Jean L. Bolognia, professor of dermatology and vice chair of clinical affairs at Yale University, New Haven, Conn., suggests that by using the all-encompassing clinical term "toxic erythema of chemotherapy," a common ground can be established between all members of a patient’s cancer treatment team, and better outcomes achieved.

In this podcast, Dr. Bolognia offers clinicians specifics for determining when a patient is experiencing a cutaneous reaction to chemotherapy or biologics vs. other skin diseases, and suggests ways to adjust treatment to lessen skin reactions. "It requires adjusting some of the misconceptions about drug eruptions," advises Dr. Bolognia. "This is a toxic reaction, not an allergic one." The distinction is important, according to Dr. Bolognia, especially if the patient is responding to their primary treatment; rather than stop a medication, the timing and dosage can be changed.

Among other tips, such as which drugs create certain drug eruptions, Dr. Bolognia reminds dermatologists and primary care clinicians including physician’s assistants that even a month after treatment, cutaneous reactions are possible.

[email protected]

On Twitter @whitneymcknight

PALM BEACH, ARUBA – Chemotherapy can trigger a host of skin presentations, the specific histologies of which may not be as recognizable to oncologists and hematologists as they would be to dermatologists and primary care physicians. Dr. Jean L. Bolognia, professor of dermatology and vice chair of clinical affairs at Yale University, New Haven, Conn., suggests that by using the all-encompassing clinical term "toxic erythema of chemotherapy," a common ground can be established between all members of a patient’s cancer treatment team, and better outcomes achieved.

In this podcast, Dr. Bolognia offers clinicians specifics for determining when a patient is experiencing a cutaneous reaction to chemotherapy or biologics vs. other skin diseases, and suggests ways to adjust treatment to lessen skin reactions. "It requires adjusting some of the misconceptions about drug eruptions," advises Dr. Bolognia. "This is a toxic reaction, not an allergic one." The distinction is important, according to Dr. Bolognia, especially if the patient is responding to their primary treatment; rather than stop a medication, the timing and dosage can be changed.

Among other tips, such as which drugs create certain drug eruptions, Dr. Bolognia reminds dermatologists and primary care clinicians including physician’s assistants that even a month after treatment, cutaneous reactions are possible.

[email protected]

On Twitter @whitneymcknight

SAN DIEGO – DEDN6526A, a new anti–endothelin B receptor antibody-drug conjugate, demonstrated safety, tolerability, and hints of clinical efficacy against different types of metastatic or unresectable melanoma, results from a phase I trial showed.

During a press briefing at the annual meeting of the American Association for Cancer Research, Dr. Jeffrey R. Infante said that anti–endothelin B receptor (ETBR), a G-protein–coupled receptor that can activate RAF/MEK signaling, is overexpressed in metastatic melanoma, compared with normal skin. Developed by Genentech using Seattle Genetics antibody-drug conjugate (ADC) technology, DEDN6526A is an ADC with the anti-mitotic agent monomethyl auristatin E (MMAE) linked to the humanized IgG1 anti-ETBR antibody and represents a targeted chemotherapy to melanoma. ETBR "regulates migration and proliferation of melanocyte precursors from the neural crest during embryonic development," explained Dr. Infante, director of the drug development program at Sarah Cannon Research Institute in Nashville, Tenn. "It is associated with malignant transformation of melanocytes and with potentiation of metastatic spread."

©2014 AACR/Todd Buchanan

A prototype ETBR assay is being developed as a potential comparison diagnostic in melanoma. The assay is used on formalin-fixed, paraffin-embedded melanoma.

In an effort to determine the maximum tolerated dose of DEDN6526A, 28 patients with metastatic or unresectable cutaneous, mucosal, or ocular melanoma received the intravenous agent every 3 weeks. The researchers collected pharmacokinetic samples and assessed tumor tissue for ETBR expression by immunohistochemistry. Clinical activity was evaluated per RECIST v1.1. (Response Evaluation Criteria in Solid Tumors version 1.1).

Dr. Infante reported that more than half of study participants had more than three prior therapies and 70% had two or more prior therapies. Eight of the patients had ocular melanoma and three of them had mucosal melanoma. Dose escalation started at 0.3 mg/kg and patients received a median of six doses of the agent. The maximum tolerated dose was determined to be 2.4 mg/kg, which is currently being tested in the expansion phase of the trial.

The most common adverse event of any grade was fatigue (57%), followed by chills (39%), alopecia (32%), diarrhea (32%), nausea (29%), decreased appetite (25%), headache (25%), and infusion-related reaction (25%). Neutropenia was the most frequent grade 3 or 4 event. "It often did not require a dose reduction, so it was manageable," Dr. Infante said.

Complete radiographic data were available on 24 patients. Among these, clinical benefit was observed in 12 of the 19 patients who were assigned to a dosing regimen of 1.8 g/kg of DEDN6526A or more. Four of the 12 patients achieved complete response (two were cases of cutaneous melanoma and two were cases of mucosal melanoma). "It did not seem to depend on whether they had a BRAF mutation or had prior treatment with ipilimumab," Dr. Infante said. The other eight patients had stable disease for at least 6 months. "If you can stay on drug for 6 months, that’s probably meaningful benefit in an early phase I trial," he commented.

Dr. Thomas Lynch, director of the Yale Cancer Center and physician-in-chief of Smilow Cancer Hospital at Yale University, New Haven, Conn., who moderated the press briefing, noted that while antibody-drug conjugates such as DEDN6526A "look very promising," the biomarker used in the trial is not fully developed yet. "It may well be that with a mature biomarker, it turns out to have good predictive value," he said.

In an unrelated presentation at the meeting, Dr. Mark Middleton presented findings from a phase I trial of IMCgp100, an investigational agent being developed by Immunocore that is comprised of an affinity-enhanced T-cell receptor specific for the HLA-A2 restricted melanoma gp100 peptide fused to an anti-CD3 antibody fragment. "What’s important about this method of targeting is that it’s very different from a lot of immunotherapies that have been reported," said Dr. Middleton, the study’s principal investigator who is professor of experimental cancer medicine at the University of Oxford (England). "Rather than targeting cell surface proteins, this is targeting the peptide HLA complex, and therefore brings in intracellular protein targets. The premise is that high affinity binding of the T-cell receptor portions of the cancer cell then leads to recruitment of T cells, formation of an immune synapse, and the release of lytic granules leading to apoptotic cell death of the cancer cell."

He and his associates conducted a phase I dose-escalation study using a standard 3+3 cohort design in melanoma patients who had disease in a variety of sites, including the lung, liver, lymphatic system, and various soft tissues. All patients received a single, 5 ng/kg dose of IMCgp100 followed by 30 days of observation. After this 30-day observation period patients could go on to have six weekly infusions followed by 4 weeks of rest if they continued to derive clinical benefit. "On establishment of the maximum tolerated dose, we specified that we would conduct an expansion cohort to explore pharmacodynamics, clinical efficacy, and safety in more detail," Dr. Middleton said, noting that a total of eight cohorts were studied. Patients had to have stage 4 or unresectable stage 3 melanoma, had to be HLA-A2 positive and have an Eastern Cooperative Oncology Group Performance Status of 0 or 1.

The researchers administered IMCgp100 as a 4-hour infusion followed by 48 hours of in-patient observation. Over that 48-hour period they conducted extensive safety evaluations and pharmacokinetic and pharmacodynamic analysis, including detailed audiometric and ophthalmic review. "Because we started with such a low dose we said that we would triple the dose in the absence of toxicity, moving to smaller increments according to safety and pharmacokinetic profile," he said.

Dose-limiting toxicities were defined as drug-related toxicities that occurred within 8 days of drug administration. Anything grade 3 or higher would be deemed as a dose-limiting toxicity.

Among the 40 patients in the trial, the mean age was 59 years and 23 were male. The researchers started to see toxicity at a dose of 45 ng/kg, "which would manifest as a rash that would endure for a few hours, perhaps into the next day," Dr. Middleton said. "At a dose of 135 ng/kg this became more widespread, albeit transient, and we therefore slowed the rate of increase between cohorts." One patient in the 405 ng/kg cohort and two patients in the 900 ng/kg cohort developed grade 3 hypotension 10-12 hours after drug administration. This in part led the researchers to declare a nontolerated dose of 900 ng/kg and a maximum tolerated dose of 600 ng/kg.

Among the first 15 patients to be treated with the maximum tolerated dose of 600 ng/kg, the most common adverse event was an itchy rash, "which is often widespread, and associated with edema, which can be periorbital and more widespread," Dr. Middleton said. "This is transient; it usually settles down within 48-72 hours and is not as severe with subsequent administration of the drug." One case of hypotension occurred. The patient recovered after intensive supportive care. Evaluation of pharmacokinetics showed evidence of lymphocyte trafficking, neutrophilia, and a rise in C-reactive protein.

Efficacy results from 10 of the first 15 patients to be treated with the maximum tolerated dose of 600 ng/kg showed evidence of "significant and durable clinical responses, particularly in two patients who were treated in the dose escalation phase," he said. Those two patients met the RECIST criteria for response.

Dr. Middleton and his associates are continuing study expansion at the current dose level, with mandated tumor biopsies before treatment, and testing a weekly dosing arm. The goal is to identify the optimal dosing regimen for IMCgp100. The trial is expected to be complete in 2015.

The study was funded by Immunocore. Dr. Middleton disclosed that he is a consultant for Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, GSK, Millenium, and Roche.

The study of DEDN6526A was funded by Genentech. Dr. Infante said that he had no relevant financial conflicts to disclose.

Dr. Lynch disclosed that he is on the board of directors for Bristol Myers Squibb and Infinity Pharmaceuticals, and that he receives honoraria and stock from both companies. He is also on the scientific advisory board for Arvinas, and he receives honoraria and stock from that company. In addition, Dr. Lynch is a patent holder with Partners Healthcare for an EGFR mutation–testing patent and receives royalties.

[email protected]

SAN DIEGO – DEDN6526A, a new anti–endothelin B receptor antibody-drug conjugate, demonstrated safety, tolerability, and hints of clinical efficacy against different types of metastatic or unresectable melanoma, results from a phase I trial showed.

During a press briefing at the annual meeting of the American Association for Cancer Research, Dr. Jeffrey R. Infante said that anti–endothelin B receptor (ETBR), a G-protein–coupled receptor that can activate RAF/MEK signaling, is overexpressed in metastatic melanoma, compared with normal skin. Developed by Genentech using Seattle Genetics antibody-drug conjugate (ADC) technology, DEDN6526A is an ADC with the anti-mitotic agent monomethyl auristatin E (MMAE) linked to the humanized IgG1 anti-ETBR antibody and represents a targeted chemotherapy to melanoma. ETBR "regulates migration and proliferation of melanocyte precursors from the neural crest during embryonic development," explained Dr. Infante, director of the drug development program at Sarah Cannon Research Institute in Nashville, Tenn. "It is associated with malignant transformation of melanocytes and with potentiation of metastatic spread."

©2014 AACR/Todd Buchanan

A prototype ETBR assay is being developed as a potential comparison diagnostic in melanoma. The assay is used on formalin-fixed, paraffin-embedded melanoma.

In an effort to determine the maximum tolerated dose of DEDN6526A, 28 patients with metastatic or unresectable cutaneous, mucosal, or ocular melanoma received the intravenous agent every 3 weeks. The researchers collected pharmacokinetic samples and assessed tumor tissue for ETBR expression by immunohistochemistry. Clinical activity was evaluated per RECIST v1.1. (Response Evaluation Criteria in Solid Tumors version 1.1).

Dr. Infante reported that more than half of study participants had more than three prior therapies and 70% had two or more prior therapies. Eight of the patients had ocular melanoma and three of them had mucosal melanoma. Dose escalation started at 0.3 mg/kg and patients received a median of six doses of the agent. The maximum tolerated dose was determined to be 2.4 mg/kg, which is currently being tested in the expansion phase of the trial.

The most common adverse event of any grade was fatigue (57%), followed by chills (39%), alopecia (32%), diarrhea (32%), nausea (29%), decreased appetite (25%), headache (25%), and infusion-related reaction (25%). Neutropenia was the most frequent grade 3 or 4 event. "It often did not require a dose reduction, so it was manageable," Dr. Infante said.

Complete radiographic data were available on 24 patients. Among these, clinical benefit was observed in 12 of the 19 patients who were assigned to a dosing regimen of 1.8 g/kg of DEDN6526A or more. Four of the 12 patients achieved complete response (two were cases of cutaneous melanoma and two were cases of mucosal melanoma). "It did not seem to depend on whether they had a BRAF mutation or had prior treatment with ipilimumab," Dr. Infante said. The other eight patients had stable disease for at least 6 months. "If you can stay on drug for 6 months, that’s probably meaningful benefit in an early phase I trial," he commented.

Dr. Thomas Lynch, director of the Yale Cancer Center and physician-in-chief of Smilow Cancer Hospital at Yale University, New Haven, Conn., who moderated the press briefing, noted that while antibody-drug conjugates such as DEDN6526A "look very promising," the biomarker used in the trial is not fully developed yet. "It may well be that with a mature biomarker, it turns out to have good predictive value," he said.

In an unrelated presentation at the meeting, Dr. Mark Middleton presented findings from a phase I trial of IMCgp100, an investigational agent being developed by Immunocore that is comprised of an affinity-enhanced T-cell receptor specific for the HLA-A2 restricted melanoma gp100 peptide fused to an anti-CD3 antibody fragment. "What’s important about this method of targeting is that it’s very different from a lot of immunotherapies that have been reported," said Dr. Middleton, the study’s principal investigator who is professor of experimental cancer medicine at the University of Oxford (England). "Rather than targeting cell surface proteins, this is targeting the peptide HLA complex, and therefore brings in intracellular protein targets. The premise is that high affinity binding of the T-cell receptor portions of the cancer cell then leads to recruitment of T cells, formation of an immune synapse, and the release of lytic granules leading to apoptotic cell death of the cancer cell."

He and his associates conducted a phase I dose-escalation study using a standard 3+3 cohort design in melanoma patients who had disease in a variety of sites, including the lung, liver, lymphatic system, and various soft tissues. All patients received a single, 5 ng/kg dose of IMCgp100 followed by 30 days of observation. After this 30-day observation period patients could go on to have six weekly infusions followed by 4 weeks of rest if they continued to derive clinical benefit. "On establishment of the maximum tolerated dose, we specified that we would conduct an expansion cohort to explore pharmacodynamics, clinical efficacy, and safety in more detail," Dr. Middleton said, noting that a total of eight cohorts were studied. Patients had to have stage 4 or unresectable stage 3 melanoma, had to be HLA-A2 positive and have an Eastern Cooperative Oncology Group Performance Status of 0 or 1.

The researchers administered IMCgp100 as a 4-hour infusion followed by 48 hours of in-patient observation. Over that 48-hour period they conducted extensive safety evaluations and pharmacokinetic and pharmacodynamic analysis, including detailed audiometric and ophthalmic review. "Because we started with such a low dose we said that we would triple the dose in the absence of toxicity, moving to smaller increments according to safety and pharmacokinetic profile," he said.

Dose-limiting toxicities were defined as drug-related toxicities that occurred within 8 days of drug administration. Anything grade 3 or higher would be deemed as a dose-limiting toxicity.

Among the 40 patients in the trial, the mean age was 59 years and 23 were male. The researchers started to see toxicity at a dose of 45 ng/kg, "which would manifest as a rash that would endure for a few hours, perhaps into the next day," Dr. Middleton said. "At a dose of 135 ng/kg this became more widespread, albeit transient, and we therefore slowed the rate of increase between cohorts." One patient in the 405 ng/kg cohort and two patients in the 900 ng/kg cohort developed grade 3 hypotension 10-12 hours after drug administration. This in part led the researchers to declare a nontolerated dose of 900 ng/kg and a maximum tolerated dose of 600 ng/kg.

Among the first 15 patients to be treated with the maximum tolerated dose of 600 ng/kg, the most common adverse event was an itchy rash, "which is often widespread, and associated with edema, which can be periorbital and more widespread," Dr. Middleton said. "This is transient; it usually settles down within 48-72 hours and is not as severe with subsequent administration of the drug." One case of hypotension occurred. The patient recovered after intensive supportive care. Evaluation of pharmacokinetics showed evidence of lymphocyte trafficking, neutrophilia, and a rise in C-reactive protein.

Efficacy results from 10 of the first 15 patients to be treated with the maximum tolerated dose of 600 ng/kg showed evidence of "significant and durable clinical responses, particularly in two patients who were treated in the dose escalation phase," he said. Those two patients met the RECIST criteria for response.

Dr. Middleton and his associates are continuing study expansion at the current dose level, with mandated tumor biopsies before treatment, and testing a weekly dosing arm. The goal is to identify the optimal dosing regimen for IMCgp100. The trial is expected to be complete in 2015.

The study was funded by Immunocore. Dr. Middleton disclosed that he is a consultant for Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, GSK, Millenium, and Roche.

The study of DEDN6526A was funded by Genentech. Dr. Infante said that he had no relevant financial conflicts to disclose.

Dr. Lynch disclosed that he is on the board of directors for Bristol Myers Squibb and Infinity Pharmaceuticals, and that he receives honoraria and stock from both companies. He is also on the scientific advisory board for Arvinas, and he receives honoraria and stock from that company. In addition, Dr. Lynch is a patent holder with Partners Healthcare for an EGFR mutation–testing patent and receives royalties.

[email protected]

SAN DIEGO – DEDN6526A, a new anti–endothelin B receptor antibody-drug conjugate, demonstrated safety, tolerability, and hints of clinical efficacy against different types of metastatic or unresectable melanoma, results from a phase I trial showed.

During a press briefing at the annual meeting of the American Association for Cancer Research, Dr. Jeffrey R. Infante said that anti–endothelin B receptor (ETBR), a G-protein–coupled receptor that can activate RAF/MEK signaling, is overexpressed in metastatic melanoma, compared with normal skin. Developed by Genentech using Seattle Genetics antibody-drug conjugate (ADC) technology, DEDN6526A is an ADC with the anti-mitotic agent monomethyl auristatin E (MMAE) linked to the humanized IgG1 anti-ETBR antibody and represents a targeted chemotherapy to melanoma. ETBR "regulates migration and proliferation of melanocyte precursors from the neural crest during embryonic development," explained Dr. Infante, director of the drug development program at Sarah Cannon Research Institute in Nashville, Tenn. "It is associated with malignant transformation of melanocytes and with potentiation of metastatic spread."

©2014 AACR/Todd Buchanan

A prototype ETBR assay is being developed as a potential comparison diagnostic in melanoma. The assay is used on formalin-fixed, paraffin-embedded melanoma.

In an effort to determine the maximum tolerated dose of DEDN6526A, 28 patients with metastatic or unresectable cutaneous, mucosal, or ocular melanoma received the intravenous agent every 3 weeks. The researchers collected pharmacokinetic samples and assessed tumor tissue for ETBR expression by immunohistochemistry. Clinical activity was evaluated per RECIST v1.1. (Response Evaluation Criteria in Solid Tumors version 1.1).

Dr. Infante reported that more than half of study participants had more than three prior therapies and 70% had two or more prior therapies. Eight of the patients had ocular melanoma and three of them had mucosal melanoma. Dose escalation started at 0.3 mg/kg and patients received a median of six doses of the agent. The maximum tolerated dose was determined to be 2.4 mg/kg, which is currently being tested in the expansion phase of the trial.

The most common adverse event of any grade was fatigue (57%), followed by chills (39%), alopecia (32%), diarrhea (32%), nausea (29%), decreased appetite (25%), headache (25%), and infusion-related reaction (25%). Neutropenia was the most frequent grade 3 or 4 event. "It often did not require a dose reduction, so it was manageable," Dr. Infante said.

Complete radiographic data were available on 24 patients. Among these, clinical benefit was observed in 12 of the 19 patients who were assigned to a dosing regimen of 1.8 g/kg of DEDN6526A or more. Four of the 12 patients achieved complete response (two were cases of cutaneous melanoma and two were cases of mucosal melanoma). "It did not seem to depend on whether they had a BRAF mutation or had prior treatment with ipilimumab," Dr. Infante said. The other eight patients had stable disease for at least 6 months. "If you can stay on drug for 6 months, that’s probably meaningful benefit in an early phase I trial," he commented.

Dr. Thomas Lynch, director of the Yale Cancer Center and physician-in-chief of Smilow Cancer Hospital at Yale University, New Haven, Conn., who moderated the press briefing, noted that while antibody-drug conjugates such as DEDN6526A "look very promising," the biomarker used in the trial is not fully developed yet. "It may well be that with a mature biomarker, it turns out to have good predictive value," he said.

In an unrelated presentation at the meeting, Dr. Mark Middleton presented findings from a phase I trial of IMCgp100, an investigational agent being developed by Immunocore that is comprised of an affinity-enhanced T-cell receptor specific for the HLA-A2 restricted melanoma gp100 peptide fused to an anti-CD3 antibody fragment. "What’s important about this method of targeting is that it’s very different from a lot of immunotherapies that have been reported," said Dr. Middleton, the study’s principal investigator who is professor of experimental cancer medicine at the University of Oxford (England). "Rather than targeting cell surface proteins, this is targeting the peptide HLA complex, and therefore brings in intracellular protein targets. The premise is that high affinity binding of the T-cell receptor portions of the cancer cell then leads to recruitment of T cells, formation of an immune synapse, and the release of lytic granules leading to apoptotic cell death of the cancer cell."

He and his associates conducted a phase I dose-escalation study using a standard 3+3 cohort design in melanoma patients who had disease in a variety of sites, including the lung, liver, lymphatic system, and various soft tissues. All patients received a single, 5 ng/kg dose of IMCgp100 followed by 30 days of observation. After this 30-day observation period patients could go on to have six weekly infusions followed by 4 weeks of rest if they continued to derive clinical benefit. "On establishment of the maximum tolerated dose, we specified that we would conduct an expansion cohort to explore pharmacodynamics, clinical efficacy, and safety in more detail," Dr. Middleton said, noting that a total of eight cohorts were studied. Patients had to have stage 4 or unresectable stage 3 melanoma, had to be HLA-A2 positive and have an Eastern Cooperative Oncology Group Performance Status of 0 or 1.

The researchers administered IMCgp100 as a 4-hour infusion followed by 48 hours of in-patient observation. Over that 48-hour period they conducted extensive safety evaluations and pharmacokinetic and pharmacodynamic analysis, including detailed audiometric and ophthalmic review. "Because we started with such a low dose we said that we would triple the dose in the absence of toxicity, moving to smaller increments according to safety and pharmacokinetic profile," he said.

Dose-limiting toxicities were defined as drug-related toxicities that occurred within 8 days of drug administration. Anything grade 3 or higher would be deemed as a dose-limiting toxicity.

Among the 40 patients in the trial, the mean age was 59 years and 23 were male. The researchers started to see toxicity at a dose of 45 ng/kg, "which would manifest as a rash that would endure for a few hours, perhaps into the next day," Dr. Middleton said. "At a dose of 135 ng/kg this became more widespread, albeit transient, and we therefore slowed the rate of increase between cohorts." One patient in the 405 ng/kg cohort and two patients in the 900 ng/kg cohort developed grade 3 hypotension 10-12 hours after drug administration. This in part led the researchers to declare a nontolerated dose of 900 ng/kg and a maximum tolerated dose of 600 ng/kg.

Among the first 15 patients to be treated with the maximum tolerated dose of 600 ng/kg, the most common adverse event was an itchy rash, "which is often widespread, and associated with edema, which can be periorbital and more widespread," Dr. Middleton said. "This is transient; it usually settles down within 48-72 hours and is not as severe with subsequent administration of the drug." One case of hypotension occurred. The patient recovered after intensive supportive care. Evaluation of pharmacokinetics showed evidence of lymphocyte trafficking, neutrophilia, and a rise in C-reactive protein.

Efficacy results from 10 of the first 15 patients to be treated with the maximum tolerated dose of 600 ng/kg showed evidence of "significant and durable clinical responses, particularly in two patients who were treated in the dose escalation phase," he said. Those two patients met the RECIST criteria for response.

Dr. Middleton and his associates are continuing study expansion at the current dose level, with mandated tumor biopsies before treatment, and testing a weekly dosing arm. The goal is to identify the optimal dosing regimen for IMCgp100. The trial is expected to be complete in 2015.

The study was funded by Immunocore. Dr. Middleton disclosed that he is a consultant for Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, GSK, Millenium, and Roche.

The study of DEDN6526A was funded by Genentech. Dr. Infante said that he had no relevant financial conflicts to disclose.

Dr. Lynch disclosed that he is on the board of directors for Bristol Myers Squibb and Infinity Pharmaceuticals, and that he receives honoraria and stock from both companies. He is also on the scientific advisory board for Arvinas, and he receives honoraria and stock from that company. In addition, Dr. Lynch is a patent holder with Partners Healthcare for an EGFR mutation–testing patent and receives royalties.

[email protected]

WAIKOLOA, HAWAII – Momentum is building – perhaps unstoppably – for creation of a national, population-based melanoma screening program.

"Demand for screening is going up as we speak. The incidence of melanoma is going up dramatically, and it’s really important to understand that this is happening in the absence of formal screening for melanoma. So imagine what would happen if we did screen for melanoma routinely," Dr. Allan C. Halpern observed at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Also, public awareness is increasing dramatically.

"We’ve spent a lot of time as dermatologists educating the public. And there may be as many as a million people walking around the U.S. right now who’ve personally had melanoma. We want to see them in follow-up visits, and their family members want to see us as well," said Dr. Halpern, chief of the dermatology service at Memorial Sloan Kettering Cancer Center in New York.

The current position of the U.S. Preventive Services Task Force (Ann. Intern. Med. 2009;150:194-8), the American Cancer Society, and other influential organizations is that formal guidelines for population-based screening for melanoma are not warranted at this time, because there is no randomized clinical trial evidence of net benefit. That position could change, however, even in the absence of such evidence. For example, the U.S. Preventive Services Task Force strongly supports cervical cancer screening, even though it has never been subjected to a randomized trial. The task force became convinced that cervical cancer screening works on the basis of observational data showing that by the time 80% of women were screened, mortality due to cervical cancer dropped by nearly 50%, Dr. Halpern noted.

The ‘extraordinary’ German example

The ongoing German national experience with melanoma screening may provide a big push for a shift in U.S. health policy in favor of routine screening for melanoma, according to Dr. Halpern.

The German melanoma screening program is one of the most extraordinary stories in dermatology, he said. The program is mainly the work of one determined and persuasive German dermatologist – Dr. Eckhard Breitbart – who has been pushing for melanoma screening in Germany for 45 years. Dr. Breitbart received funding for a pilot study conducted in Germany’s northernmost state, Schleswig-Holstein. The state’s primary care physicians were persuaded to conduct the first-tier screening of all Schleswig-Holstein residents. They received a financial incentive on a per-case basis, provided they first completed an 8-hour training course. The bottom line: After just 2 years of screening, mortality caused by melanoma dropped by 48% over the next 7 years while remaining unchanged in the neighboring states (Cancer 2012;118:5395-402).

Armed with the data, Dr. Breitbart persuaded the German federal government to expand screening nationally. That program began in 2005.

"I don’t think melanoma mortality will come down by 50% across all of Germany, but if the German data show it comes down by 20%-30%, then it’s the cervical cancer story revisited. I think that would be very strong endorsement that screening for melanoma can save lives," Dr. Halpern said.

He injected a cautionary note, however.

"I must warn you; the German experience may not give us definitive answers. It turns out that Eckhard Breitbart was so persuasive when he went to convince the German government to do the screening program that they ‘knew’ for a fact that it was going to work. So they didn’t allocate any money for an assessment of whether it actually works," Dr. Halpern explained.

Also, the study was limited by the German government’s concern about medical records privacy.

"Trying to get the data on who was screened versus who got melanoma and died of it is proving amazingly difficult. There are actually a bunch of melanoma experts here in the states, including Marty Weinstock and Alan Geller, who have been working closely with the German group to try to get some of the data. We’ll just have to wait and see how the German experience plays out," Dr. Halpern continued.

As pressure for routine melanoma screening mounts in the United States, it’s apparent that there is a major supply-and-demand issue involved. The supply of the medical dermatology workforce is shrinking relative to the growing demand, Dr. Halpern said. Going forward, the most promising solution in his view is to train primary care physicians and physician extenders to perform the screening, as is done in Germany. There is an enormous opportunity here for these nondermatologists to harness the emerging automated imaging and molecular sensing technologies for detection of lesion changes and diagnosis of melanoma, he added.

First do no harm

Dr. Halpern offered a note of caution regarding melanoma screening: Although it sounds great in theory because it’s relatively cheap, the lesions are accessible on the surface of the skin, and there is the potential to save many life-years, it’s also imperative to consider the potential harms. Perhaps the biggest of these, Dr. Halpern said, is the psychological damage caused by turning a patient with an indolent, low-risk melanoma or nonmelanoma skin cancer into a cancer patient.

"We have to be really, really careful to look at the harms involved in screening. To my mind, one of the biggest problems of melanoma screening is the psychological harm we do by giving people cancer. I’m especially bothered about the way we do that with patients who develop melanoma in situ or microinvasive disease," he said.

"Believe me, if I had melanoma in situ or microinvasive melanoma, I would want you to find it and take if off for me. What I don’t want you to do is to turn me into a cancer patient. I don’t think that’s in the patient’s best interest whatsoever. We don’t do it intentionally, but as dermatologists we have this tendency to dramatically overplay the importance of these diagnoses," Dr. Halpern said.

Dr. Halpern reported having financial relationships with Scibase, DermTech, Caliber, and Canfield.

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

[email protected]

WAIKOLOA, HAWAII – Momentum is building – perhaps unstoppably – for creation of a national, population-based melanoma screening program.

"Demand for screening is going up as we speak. The incidence of melanoma is going up dramatically, and it’s really important to understand that this is happening in the absence of formal screening for melanoma. So imagine what would happen if we did screen for melanoma routinely," Dr. Allan C. Halpern observed at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Also, public awareness is increasing dramatically.

"We’ve spent a lot of time as dermatologists educating the public. And there may be as many as a million people walking around the U.S. right now who’ve personally had melanoma. We want to see them in follow-up visits, and their family members want to see us as well," said Dr. Halpern, chief of the dermatology service at Memorial Sloan Kettering Cancer Center in New York.

The current position of the U.S. Preventive Services Task Force (Ann. Intern. Med. 2009;150:194-8), the American Cancer Society, and other influential organizations is that formal guidelines for population-based screening for melanoma are not warranted at this time, because there is no randomized clinical trial evidence of net benefit. That position could change, however, even in the absence of such evidence. For example, the U.S. Preventive Services Task Force strongly supports cervical cancer screening, even though it has never been subjected to a randomized trial. The task force became convinced that cervical cancer screening works on the basis of observational data showing that by the time 80% of women were screened, mortality due to cervical cancer dropped by nearly 50%, Dr. Halpern noted.

The ‘extraordinary’ German example

The ongoing German national experience with melanoma screening may provide a big push for a shift in U.S. health policy in favor of routine screening for melanoma, according to Dr. Halpern.

The German melanoma screening program is one of the most extraordinary stories in dermatology, he said. The program is mainly the work of one determined and persuasive German dermatologist – Dr. Eckhard Breitbart – who has been pushing for melanoma screening in Germany for 45 years. Dr. Breitbart received funding for a pilot study conducted in Germany’s northernmost state, Schleswig-Holstein. The state’s primary care physicians were persuaded to conduct the first-tier screening of all Schleswig-Holstein residents. They received a financial incentive on a per-case basis, provided they first completed an 8-hour training course. The bottom line: After just 2 years of screening, mortality caused by melanoma dropped by 48% over the next 7 years while remaining unchanged in the neighboring states (Cancer 2012;118:5395-402).

Armed with the data, Dr. Breitbart persuaded the German federal government to expand screening nationally. That program began in 2005.

"I don’t think melanoma mortality will come down by 50% across all of Germany, but if the German data show it comes down by 20%-30%, then it’s the cervical cancer story revisited. I think that would be very strong endorsement that screening for melanoma can save lives," Dr. Halpern said.

He injected a cautionary note, however.

"I must warn you; the German experience may not give us definitive answers. It turns out that Eckhard Breitbart was so persuasive when he went to convince the German government to do the screening program that they ‘knew’ for a fact that it was going to work. So they didn’t allocate any money for an assessment of whether it actually works," Dr. Halpern explained.

Also, the study was limited by the German government’s concern about medical records privacy.

"Trying to get the data on who was screened versus who got melanoma and died of it is proving amazingly difficult. There are actually a bunch of melanoma experts here in the states, including Marty Weinstock and Alan Geller, who have been working closely with the German group to try to get some of the data. We’ll just have to wait and see how the German experience plays out," Dr. Halpern continued.

As pressure for routine melanoma screening mounts in the United States, it’s apparent that there is a major supply-and-demand issue involved. The supply of the medical dermatology workforce is shrinking relative to the growing demand, Dr. Halpern said. Going forward, the most promising solution in his view is to train primary care physicians and physician extenders to perform the screening, as is done in Germany. There is an enormous opportunity here for these nondermatologists to harness the emerging automated imaging and molecular sensing technologies for detection of lesion changes and diagnosis of melanoma, he added.

First do no harm

Dr. Halpern offered a note of caution regarding melanoma screening: Although it sounds great in theory because it’s relatively cheap, the lesions are accessible on the surface of the skin, and there is the potential to save many life-years, it’s also imperative to consider the potential harms. Perhaps the biggest of these, Dr. Halpern said, is the psychological damage caused by turning a patient with an indolent, low-risk melanoma or nonmelanoma skin cancer into a cancer patient.

"We have to be really, really careful to look at the harms involved in screening. To my mind, one of the biggest problems of melanoma screening is the psychological harm we do by giving people cancer. I’m especially bothered about the way we do that with patients who develop melanoma in situ or microinvasive disease," he said.

"Believe me, if I had melanoma in situ or microinvasive melanoma, I would want you to find it and take if off for me. What I don’t want you to do is to turn me into a cancer patient. I don’t think that’s in the patient’s best interest whatsoever. We don’t do it intentionally, but as dermatologists we have this tendency to dramatically overplay the importance of these diagnoses," Dr. Halpern said.

Dr. Halpern reported having financial relationships with Scibase, DermTech, Caliber, and Canfield.

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

[email protected]

WAIKOLOA, HAWAII – Momentum is building – perhaps unstoppably – for creation of a national, population-based melanoma screening program.

"Demand for screening is going up as we speak. The incidence of melanoma is going up dramatically, and it’s really important to understand that this is happening in the absence of formal screening for melanoma. So imagine what would happen if we did screen for melanoma routinely," Dr. Allan C. Halpern observed at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Also, public awareness is increasing dramatically.

"We’ve spent a lot of time as dermatologists educating the public. And there may be as many as a million people walking around the U.S. right now who’ve personally had melanoma. We want to see them in follow-up visits, and their family members want to see us as well," said Dr. Halpern, chief of the dermatology service at Memorial Sloan Kettering Cancer Center in New York.

The current position of the U.S. Preventive Services Task Force (Ann. Intern. Med. 2009;150:194-8), the American Cancer Society, and other influential organizations is that formal guidelines for population-based screening for melanoma are not warranted at this time, because there is no randomized clinical trial evidence of net benefit. That position could change, however, even in the absence of such evidence. For example, the U.S. Preventive Services Task Force strongly supports cervical cancer screening, even though it has never been subjected to a randomized trial. The task force became convinced that cervical cancer screening works on the basis of observational data showing that by the time 80% of women were screened, mortality due to cervical cancer dropped by nearly 50%, Dr. Halpern noted.

The ‘extraordinary’ German example

The ongoing German national experience with melanoma screening may provide a big push for a shift in U.S. health policy in favor of routine screening for melanoma, according to Dr. Halpern.

The German melanoma screening program is one of the most extraordinary stories in dermatology, he said. The program is mainly the work of one determined and persuasive German dermatologist – Dr. Eckhard Breitbart – who has been pushing for melanoma screening in Germany for 45 years. Dr. Breitbart received funding for a pilot study conducted in Germany’s northernmost state, Schleswig-Holstein. The state’s primary care physicians were persuaded to conduct the first-tier screening of all Schleswig-Holstein residents. They received a financial incentive on a per-case basis, provided they first completed an 8-hour training course. The bottom line: After just 2 years of screening, mortality caused by melanoma dropped by 48% over the next 7 years while remaining unchanged in the neighboring states (Cancer 2012;118:5395-402).

Armed with the data, Dr. Breitbart persuaded the German federal government to expand screening nationally. That program began in 2005.

"I don’t think melanoma mortality will come down by 50% across all of Germany, but if the German data show it comes down by 20%-30%, then it’s the cervical cancer story revisited. I think that would be very strong endorsement that screening for melanoma can save lives," Dr. Halpern said.

He injected a cautionary note, however.

"I must warn you; the German experience may not give us definitive answers. It turns out that Eckhard Breitbart was so persuasive when he went to convince the German government to do the screening program that they ‘knew’ for a fact that it was going to work. So they didn’t allocate any money for an assessment of whether it actually works," Dr. Halpern explained.

Also, the study was limited by the German government’s concern about medical records privacy.

"Trying to get the data on who was screened versus who got melanoma and died of it is proving amazingly difficult. There are actually a bunch of melanoma experts here in the states, including Marty Weinstock and Alan Geller, who have been working closely with the German group to try to get some of the data. We’ll just have to wait and see how the German experience plays out," Dr. Halpern continued.

As pressure for routine melanoma screening mounts in the United States, it’s apparent that there is a major supply-and-demand issue involved. The supply of the medical dermatology workforce is shrinking relative to the growing demand, Dr. Halpern said. Going forward, the most promising solution in his view is to train primary care physicians and physician extenders to perform the screening, as is done in Germany. There is an enormous opportunity here for these nondermatologists to harness the emerging automated imaging and molecular sensing technologies for detection of lesion changes and diagnosis of melanoma, he added.

First do no harm

Dr. Halpern offered a note of caution regarding melanoma screening: Although it sounds great in theory because it’s relatively cheap, the lesions are accessible on the surface of the skin, and there is the potential to save many life-years, it’s also imperative to consider the potential harms. Perhaps the biggest of these, Dr. Halpern said, is the psychological damage caused by turning a patient with an indolent, low-risk melanoma or nonmelanoma skin cancer into a cancer patient.

"We have to be really, really careful to look at the harms involved in screening. To my mind, one of the biggest problems of melanoma screening is the psychological harm we do by giving people cancer. I’m especially bothered about the way we do that with patients who develop melanoma in situ or microinvasive disease," he said.

"Believe me, if I had melanoma in situ or microinvasive melanoma, I would want you to find it and take if off for me. What I don’t want you to do is to turn me into a cancer patient. I don’t think that’s in the patient’s best interest whatsoever. We don’t do it intentionally, but as dermatologists we have this tendency to dramatically overplay the importance of these diagnoses," Dr. Halpern said.

Dr. Halpern reported having financial relationships with Scibase, DermTech, Caliber, and Canfield.

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

[email protected]

DENVER - A murine monoclonal antibody had very high sensitivity and specificity for melanomas with the V600E BRAF mutation, and exhibited perfect concordance between the primary and metastatic tumors in individual patients.

In addition to being a valuable screening tool, VE1 (anti-BRAF V600E) could be an extremely useful adjunct to DNA analysis, Michelle Vernali said at the annual meeting of the American Academy of Dermatology.

"I think that the sequential use of immunohistochemistry and molecular analysis will dramatically improve sensitivity and specificity for the detection of BRAF mutations, which is essential for the effective use of BRAF inhibitors," said Ms. Vernali, a fourth-year medical student at the University of North Carolina, Chapel Hill.

According to Roche Diagnostics, the VE1 antibody has demonstrated 100% sensitivity and 99% specificity for BRAF mutations in colon cancer. In addition, it has shown high efficacy in detecting those mutations in thyroid cancer and hairy cell leukemia, and "shows promise" in non–small cell lung cancer and serous ovarian tumors.

According to the company, "The ... antibody has also been said to be a promising tool for patient stratification among individuals presenting with brain metastases."

Ms. Vernali and her colleagues examined the benefit of VE1 staining in 93 patients with metastatic melanoma. Of these, 76 had DNA pyrosequencing of either the primary (19) or metastatic lesion (57). Both primary and metastatic tumor samples were available for 17 patients.

Of the 76 patients with either primary or metastatic lesion samples, DNA pyrosequencing identified 26 that were positive for V600E and 40 that were negative. VE1 staining identified 22 positive samples and 44 negative samples, for a specificity of 100% and a sensitivity of 85%.

Sequencing also identified eight samples positive for V600K, and one each for V600R and V600Q. VE1 did not stain any of these samples.

Among the 17 patients with both primary and metastatic samples, VE1 was in 100% concordance with DNA sequencing, identifying three positive samples and 14 negative samples.

"There was little variability of strength or intensity of the staining, and very little intra-interpreter variance," Ms. Vernali said.

She proposed an algorithm for BRAF testing using VE1 with and without DNA sequencing.

· Insufficient tissue for initial DNA pyrosequencing:

– Stain with VE1.

– Identify BRAF V600E-positive or -negative patients.

· Sufficient tissue for DNA pyrosequencing:

– Stain with VE1.

– Stratify as VE1 positive or negative.

– If VE1 positive, conclude the patient is BRAF V600E positive.

– If VE1 negative, send sample for molecular sequencing to stratify into V600E positive, positive for another BRAF mutation, or BRAF negative.

This algorithm would identify V600E status in patients with tissue samples that would otherwise be insufficient for BRAF testing, she said. "If they had insufficient tissue for DNA sequencing, they could be stratified by immunohistochemistry and if positive, could be treated. Otherwise this is a population that now goes without BRAF-inhibiting therapy."

The algorithm is being tested in some sites already, she added, but needs additional validation before it can be broadly adopted.

Ms. Vernali had no financial disclosures.

[email protected]

DENVER - A murine monoclonal antibody had very high sensitivity and specificity for melanomas with the V600E BRAF mutation, and exhibited perfect concordance between the primary and metastatic tumors in individual patients.

In addition to being a valuable screening tool, VE1 (anti-BRAF V600E) could be an extremely useful adjunct to DNA analysis, Michelle Vernali said at the annual meeting of the American Academy of Dermatology.

"I think that the sequential use of immunohistochemistry and molecular analysis will dramatically improve sensitivity and specificity for the detection of BRAF mutations, which is essential for the effective use of BRAF inhibitors," said Ms. Vernali, a fourth-year medical student at the University of North Carolina, Chapel Hill.

According to Roche Diagnostics, the VE1 antibody has demonstrated 100% sensitivity and 99% specificity for BRAF mutations in colon cancer. In addition, it has shown high efficacy in detecting those mutations in thyroid cancer and hairy cell leukemia, and "shows promise" in non–small cell lung cancer and serous ovarian tumors.

According to the company, "The ... antibody has also been said to be a promising tool for patient stratification among individuals presenting with brain metastases."

Ms. Vernali and her colleagues examined the benefit of VE1 staining in 93 patients with metastatic melanoma. Of these, 76 had DNA pyrosequencing of either the primary (19) or metastatic lesion (57). Both primary and metastatic tumor samples were available for 17 patients.

Of the 76 patients with either primary or metastatic lesion samples, DNA pyrosequencing identified 26 that were positive for V600E and 40 that were negative. VE1 staining identified 22 positive samples and 44 negative samples, for a specificity of 100% and a sensitivity of 85%.

Sequencing also identified eight samples positive for V600K, and one each for V600R and V600Q. VE1 did not stain any of these samples.

Among the 17 patients with both primary and metastatic samples, VE1 was in 100% concordance with DNA sequencing, identifying three positive samples and 14 negative samples.

"There was little variability of strength or intensity of the staining, and very little intra-interpreter variance," Ms. Vernali said.

She proposed an algorithm for BRAF testing using VE1 with and without DNA sequencing.

· Insufficient tissue for initial DNA pyrosequencing:

– Stain with VE1.

– Identify BRAF V600E-positive or -negative patients.

· Sufficient tissue for DNA pyrosequencing:

– Stain with VE1.

– Stratify as VE1 positive or negative.

– If VE1 positive, conclude the patient is BRAF V600E positive.

– If VE1 negative, send sample for molecular sequencing to stratify into V600E positive, positive for another BRAF mutation, or BRAF negative.

This algorithm would identify V600E status in patients with tissue samples that would otherwise be insufficient for BRAF testing, she said. "If they had insufficient tissue for DNA sequencing, they could be stratified by immunohistochemistry and if positive, could be treated. Otherwise this is a population that now goes without BRAF-inhibiting therapy."

The algorithm is being tested in some sites already, she added, but needs additional validation before it can be broadly adopted.

Ms. Vernali had no financial disclosures.

[email protected]

DENVER - A murine monoclonal antibody had very high sensitivity and specificity for melanomas with the V600E BRAF mutation, and exhibited perfect concordance between the primary and metastatic tumors in individual patients.

In addition to being a valuable screening tool, VE1 (anti-BRAF V600E) could be an extremely useful adjunct to DNA analysis, Michelle Vernali said at the annual meeting of the American Academy of Dermatology.

"I think that the sequential use of immunohistochemistry and molecular analysis will dramatically improve sensitivity and specificity for the detection of BRAF mutations, which is essential for the effective use of BRAF inhibitors," said Ms. Vernali, a fourth-year medical student at the University of North Carolina, Chapel Hill.

According to Roche Diagnostics, the VE1 antibody has demonstrated 100% sensitivity and 99% specificity for BRAF mutations in colon cancer. In addition, it has shown high efficacy in detecting those mutations in thyroid cancer and hairy cell leukemia, and "shows promise" in non–small cell lung cancer and serous ovarian tumors.

According to the company, "The ... antibody has also been said to be a promising tool for patient stratification among individuals presenting with brain metastases."

Ms. Vernali and her colleagues examined the benefit of VE1 staining in 93 patients with metastatic melanoma. Of these, 76 had DNA pyrosequencing of either the primary (19) or metastatic lesion (57). Both primary and metastatic tumor samples were available for 17 patients.

Of the 76 patients with either primary or metastatic lesion samples, DNA pyrosequencing identified 26 that were positive for V600E and 40 that were negative. VE1 staining identified 22 positive samples and 44 negative samples, for a specificity of 100% and a sensitivity of 85%.

Sequencing also identified eight samples positive for V600K, and one each for V600R and V600Q. VE1 did not stain any of these samples.

Among the 17 patients with both primary and metastatic samples, VE1 was in 100% concordance with DNA sequencing, identifying three positive samples and 14 negative samples.

"There was little variability of strength or intensity of the staining, and very little intra-interpreter variance," Ms. Vernali said.

She proposed an algorithm for BRAF testing using VE1 with and without DNA sequencing.

· Insufficient tissue for initial DNA pyrosequencing:

– Stain with VE1.

– Identify BRAF V600E-positive or -negative patients.

· Sufficient tissue for DNA pyrosequencing:

– Stain with VE1.

– Stratify as VE1 positive or negative.

– If VE1 positive, conclude the patient is BRAF V600E positive.

– If VE1 negative, send sample for molecular sequencing to stratify into V600E positive, positive for another BRAF mutation, or BRAF negative.

This algorithm would identify V600E status in patients with tissue samples that would otherwise be insufficient for BRAF testing, she said. "If they had insufficient tissue for DNA sequencing, they could be stratified by immunohistochemistry and if positive, could be treated. Otherwise this is a population that now goes without BRAF-inhibiting therapy."

The algorithm is being tested in some sites already, she added, but needs additional validation before it can be broadly adopted.

Ms. Vernali had no financial disclosures.

[email protected]

WASHINGTON – The Food and Drug Administration has taken too long to review and approve new sunscreen ingredients and should be required to clear its current backlog within 8 months and review new products within 11 months, members of Congress said at a hearing April 7.

"Everyone seems to agree that the current system for approving sunscreen ingredients is broken," Rep. Fred Upton (R-Mich.), chairman of the House Energy & Commerce Committee, said at a hearing of his committee’s Subcommittee on Health. H.R. 4250, the Sunscreen Innovation Act, "would help provide a solution to the current backlog of sunscreen ingredients pending at the FDA."

Ingram Publishing/Thinkstockphotos.com

Currently, eight sunscreen ingredients are under review by the FDA, many of which have been approved for use in other countries; some reviews have been ongoing for 3-11 years.

H.R. 4250 was introduced March 13 in the House by Rep. Ed Whitfield (R-Ky.) and Rep. John Dingell (D-Mich.) and as S. 2141 the same day in the Senate by Sen. Jack Reed (D-R.I.) and Sen. Johnny Isakson (R-Ga.).

In addition to eliminating the backlog, the bill would align the sunscreen review process more closely with the new-drug and device approval process. Under the legislation, the FDA Nonprescription Drugs Advisory Committee would review the safety and efficacy of the ingredient and make a recommendation on approval. The FDA would have 45 days to make the final decision for approval.

Rep. Henry Waxman (D-Calif.) said that he worried this would essentially give an advisory committee the power to make an approval decision if the FDA did not act. That would set a bad precedent, said Rep. Waxman, who added that he otherwise supported the Sunscreen Innovation Act.

The American Academy of Dermatology Association supported the legislation.

"A more timely review process has the potential to reduce Americans’ risk for skin cancer by ensuring that they have access to the safest, most effective sunscreens available," Dr. Brett M. Coldiron, AAD president, said in a statement.

Dr. Janet Woodcock, director of the FDA Center for Drug Evaluation and Research, said that she agreed that the process should be modernized and that it was no longer serving consumers, manufacturers, or the agency itself.

As Americans have gone from occasional and limited use of sunscreen products to year-round and heavier use of them, new questions have been raised about the short- and long-term effects of these products, Dr. Woodcock said. The FDA "has been actively examining the important scientific questions," such as whether there is systemic exposure to an ingredient, or if an ingredient might be an endocrine disrupter.

The FDA recently sent letters to the makers of two sunscreen ingredients – amiloxate and diethylhexyl butamido triazone – noting that the evidence is not sufficient to establish safety and efficacy, Dr. Woodcock said. The agency is still reviewing six other sunscreen ingredients.

The FDA will hold a public hearing later this year to clarify what information it is seeking to establish the safety and efficacy of sunscreen ingredients, she added.

[email protected] On Twitter @aliciaault

WASHINGTON – The Food and Drug Administration has taken too long to review and approve new sunscreen ingredients and should be required to clear its current backlog within 8 months and review new products within 11 months, members of Congress said at a hearing April 7.

"Everyone seems to agree that the current system for approving sunscreen ingredients is broken," Rep. Fred Upton (R-Mich.), chairman of the House Energy & Commerce Committee, said at a hearing of his committee’s Subcommittee on Health. H.R. 4250, the Sunscreen Innovation Act, "would help provide a solution to the current backlog of sunscreen ingredients pending at the FDA."

Ingram Publishing/Thinkstockphotos.com

Currently, eight sunscreen ingredients are under review by the FDA, many of which have been approved for use in other countries; some reviews have been ongoing for 3-11 years.

H.R. 4250 was introduced March 13 in the House by Rep. Ed Whitfield (R-Ky.) and Rep. John Dingell (D-Mich.) and as S. 2141 the same day in the Senate by Sen. Jack Reed (D-R.I.) and Sen. Johnny Isakson (R-Ga.).

In addition to eliminating the backlog, the bill would align the sunscreen review process more closely with the new-drug and device approval process. Under the legislation, the FDA Nonprescription Drugs Advisory Committee would review the safety and efficacy of the ingredient and make a recommendation on approval. The FDA would have 45 days to make the final decision for approval.

Rep. Henry Waxman (D-Calif.) said that he worried this would essentially give an advisory committee the power to make an approval decision if the FDA did not act. That would set a bad precedent, said Rep. Waxman, who added that he otherwise supported the Sunscreen Innovation Act.

The American Academy of Dermatology Association supported the legislation.

"A more timely review process has the potential to reduce Americans’ risk for skin cancer by ensuring that they have access to the safest, most effective sunscreens available," Dr. Brett M. Coldiron, AAD president, said in a statement.

Dr. Janet Woodcock, director of the FDA Center for Drug Evaluation and Research, said that she agreed that the process should be modernized and that it was no longer serving consumers, manufacturers, or the agency itself.

As Americans have gone from occasional and limited use of sunscreen products to year-round and heavier use of them, new questions have been raised about the short- and long-term effects of these products, Dr. Woodcock said. The FDA "has been actively examining the important scientific questions," such as whether there is systemic exposure to an ingredient, or if an ingredient might be an endocrine disrupter.

The FDA recently sent letters to the makers of two sunscreen ingredients – amiloxate and diethylhexyl butamido triazone – noting that the evidence is not sufficient to establish safety and efficacy, Dr. Woodcock said. The agency is still reviewing six other sunscreen ingredients.

The FDA will hold a public hearing later this year to clarify what information it is seeking to establish the safety and efficacy of sunscreen ingredients, she added.

[email protected] On Twitter @aliciaault

WASHINGTON – The Food and Drug Administration has taken too long to review and approve new sunscreen ingredients and should be required to clear its current backlog within 8 months and review new products within 11 months, members of Congress said at a hearing April 7.

"Everyone seems to agree that the current system for approving sunscreen ingredients is broken," Rep. Fred Upton (R-Mich.), chairman of the House Energy & Commerce Committee, said at a hearing of his committee’s Subcommittee on Health. H.R. 4250, the Sunscreen Innovation Act, "would help provide a solution to the current backlog of sunscreen ingredients pending at the FDA."

Ingram Publishing/Thinkstockphotos.com

Currently, eight sunscreen ingredients are under review by the FDA, many of which have been approved for use in other countries; some reviews have been ongoing for 3-11 years.

H.R. 4250 was introduced March 13 in the House by Rep. Ed Whitfield (R-Ky.) and Rep. John Dingell (D-Mich.) and as S. 2141 the same day in the Senate by Sen. Jack Reed (D-R.I.) and Sen. Johnny Isakson (R-Ga.).

In addition to eliminating the backlog, the bill would align the sunscreen review process more closely with the new-drug and device approval process. Under the legislation, the FDA Nonprescription Drugs Advisory Committee would review the safety and efficacy of the ingredient and make a recommendation on approval. The FDA would have 45 days to make the final decision for approval.

Rep. Henry Waxman (D-Calif.) said that he worried this would essentially give an advisory committee the power to make an approval decision if the FDA did not act. That would set a bad precedent, said Rep. Waxman, who added that he otherwise supported the Sunscreen Innovation Act.

The American Academy of Dermatology Association supported the legislation.

"A more timely review process has the potential to reduce Americans’ risk for skin cancer by ensuring that they have access to the safest, most effective sunscreens available," Dr. Brett M. Coldiron, AAD president, said in a statement.

Dr. Janet Woodcock, director of the FDA Center for Drug Evaluation and Research, said that she agreed that the process should be modernized and that it was no longer serving consumers, manufacturers, or the agency itself.

As Americans have gone from occasional and limited use of sunscreen products to year-round and heavier use of them, new questions have been raised about the short- and long-term effects of these products, Dr. Woodcock said. The FDA "has been actively examining the important scientific questions," such as whether there is systemic exposure to an ingredient, or if an ingredient might be an endocrine disrupter.

The FDA recently sent letters to the makers of two sunscreen ingredients – amiloxate and diethylhexyl butamido triazone – noting that the evidence is not sufficient to establish safety and efficacy, Dr. Woodcock said. The agency is still reviewing six other sunscreen ingredients.

The FDA will hold a public hearing later this year to clarify what information it is seeking to establish the safety and efficacy of sunscreen ingredients, she added.

[email protected] On Twitter @aliciaault

SAN DIEGO – Preliminary findings from two studies presented at the annual meeting of the American Association for Cancer Research suggest that cancer patients whose tumors contained the protein PD-L1 responded favorably to treatment with the investigational checkpoint inhibitor MK-3475.

A highly selective anti–PD-1 immunotherapy being developed by Merck, MK-3475 is designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein.

Both studies are analyses from the ongoing phase 1B KEYNOTE-001 study. In the first analysis, researchers led by Dr. Adil I. Daud evaluated tumor samples from 195 patients with late-stage melanoma who received MK-3475 at three different doses: 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 2 mg/kg every 3 weeks. Some of the patients had received prior treatment with ipilimumab.

Dr. Daud, codirector of the University of California, San Francisco, melanoma center and director of melanoma clinical research at the UCSF Helen Diller Family Comprehensive Cancer Center, and his associates measured the amount of PD-L1 in the tumor samples and considered them PD-L1 positive if at least 1 cell/100 tumors cells stained by immunohistochemistry contained the protein. They also used multiplex flow cytometry to assess absolute CD4 and CD8 T-cell counts and the percentage of activated CD4 and CD8 T-cell counts in peripheral blood.

All study participants had a new tumor biopsy within 2 months before the first dose of MK-3475. Their mean age was 63 years, 76% were male, and 76% had BRAF wild-type tumors. Of the 125 evaluable tumor samples, 89 (71%) were PD-L1 positive and 36 were PD-L1 negative. Disease did not progress for about 50 weeks among patients with PD-L1–positive tumors, compared with about 12 weeks among those with PD-L1–negative tumors. Among the entire study population, the overall response rate was 40%, "which is high for immunotherapy," Dr. Daud said during a press briefing.

Based on cut point of at least 1 cell/100 tumors cells, the response rate among patients with PD-L1–positive tumors was 49%, compared with 13% among patients with PD-L1–negative tumors (P = .0007). At 6 months, 57% of patients with PD-L1–positive tumors had no disease progression, compared with 35% of those whose tumors were PD-L1 negative (P = 0.0051).

Between baseline and week 6, the researchers observed a significant median increase in the percentage of CD8-positive CD4-positive T cells (14.6% vs. 15.7%, respectively) though no significant change in the absolute numbers of circulating T cells was observed.

"Given the high prevalence of PD-L1–positive tumors, the clinical utility of PD-L1 expression in melanoma is not clear at this point, because unselected patients have such a high level of response," Dr. Daud said. Changes in T-cell subtype distribution as a pharmacodynamic marker "supports the proposed MK-3475 mechanism of action."

He characterized the study as "a good foundation to build on, and we think that ongoing studies looking at larger clinical trials will help clarify the role of PD-L1 expression in terms of correlating with response of patients treated with MK-3475. Clinical development of MK-3475, both as monotherapy and as part of combination strategies, is ongoing in multiple solid tumors and hematologic malignancies."

In the second study, Dr. Leena Gandhi presented extended data from an earlier trial of 38 patients with non–small cell lung cancer who were treated with MK-3475. That trial found that higher levels of PD-L1 expression "appeared to correlate with an increased response to MK-3475," Dr. Gandhi, a thoracic oncologist at the Dana-Farber Cancer Institute, Boston, said during a press briefing. The purpose of the current analysis, which included 146 patients, was to determine an optimal cut point for defining whether a tumor is likely to respond to MK-3475 therapy or not. The patients received the agent at three different doses: 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks. Tumors were assessed by imaging every 9 weeks and by RECIST 1.1 (Response Evaluation Criteria in Solid Tumors).

Dr. Gandhi and her associates found that PD-L1 levels of greater than 50% as measured by immunohistochemistry was the best cut-off point for determining whether a tumor is likely to respond to MK-3475. Six months after starting treatment, 41% of patients with tumors that contained high levels of PD-L1 prior to treatment had no disease progression, compared with 17% of those whose tumors contained low levels of PD-L1 (hazard ratio, 0.53; P = .004). This finding is "based on very small numbers of patients with long-term follow-up, so we expect that the final progression-free survival differences may change over time with additional patients," Dr. Gandhi noted.

As for overall survival, 72% of patients with tumors that contained high levels of PD-L1 were alive at 6 months, compared with 53% of those whose tumors contained low levels of PD-L1. This difference trended toward statistical significance (HR, 0.65; P = .134) and may also change as data from additional patients are realized, she said.

Dr. Gandhi noted that data from two ongoing studies will be used to "further explore the relationship between tumor PD-L1 expression and MK-3475 activity in NSCLC patients."

In an interview, Dr. Patricia M. LoRusso, director of the Center for Translational Therapeutics at Wayne State University’s Karmanos Cancer Institute, Detroit, characterized the MK-3475 biomarker as "maturing, but I still think it’s under investigation. I still think we have a ways to go in identifying the best predictive biomarker. I don’t think it’s 100% foolproof by any means."

Both studies were funded by Merck. Dr. Daud disclosed that he has served on the advisory board of Merck and GlaxoSmithKline. Dr. Gandhi said that she had no relevant financial conflicts to disclose.

Dr. LoRusso disclosed that she has received research funding from Agios Pharmaceuticals.

[email protected]

SAN DIEGO – Preliminary findings from two studies presented at the annual meeting of the American Association for Cancer Research suggest that cancer patients whose tumors contained the protein PD-L1 responded favorably to treatment with the investigational checkpoint inhibitor MK-3475.

A highly selective anti–PD-1 immunotherapy being developed by Merck, MK-3475 is designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein.

Both studies are analyses from the ongoing phase 1B KEYNOTE-001 study. In the first analysis, researchers led by Dr. Adil I. Daud evaluated tumor samples from 195 patients with late-stage melanoma who received MK-3475 at three different doses: 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 2 mg/kg every 3 weeks. Some of the patients had received prior treatment with ipilimumab.

Dr. Daud, codirector of the University of California, San Francisco, melanoma center and director of melanoma clinical research at the UCSF Helen Diller Family Comprehensive Cancer Center, and his associates measured the amount of PD-L1 in the tumor samples and considered them PD-L1 positive if at least 1 cell/100 tumors cells stained by immunohistochemistry contained the protein. They also used multiplex flow cytometry to assess absolute CD4 and CD8 T-cell counts and the percentage of activated CD4 and CD8 T-cell counts in peripheral blood.

All study participants had a new tumor biopsy within 2 months before the first dose of MK-3475. Their mean age was 63 years, 76% were male, and 76% had BRAF wild-type tumors. Of the 125 evaluable tumor samples, 89 (71%) were PD-L1 positive and 36 were PD-L1 negative. Disease did not progress for about 50 weeks among patients with PD-L1–positive tumors, compared with about 12 weeks among those with PD-L1–negative tumors. Among the entire study population, the overall response rate was 40%, "which is high for immunotherapy," Dr. Daud said during a press briefing.

Based on cut point of at least 1 cell/100 tumors cells, the response rate among patients with PD-L1–positive tumors was 49%, compared with 13% among patients with PD-L1–negative tumors (P = .0007). At 6 months, 57% of patients with PD-L1–positive tumors had no disease progression, compared with 35% of those whose tumors were PD-L1 negative (P = 0.0051).

Between baseline and week 6, the researchers observed a significant median increase in the percentage of CD8-positive CD4-positive T cells (14.6% vs. 15.7%, respectively) though no significant change in the absolute numbers of circulating T cells was observed.

"Given the high prevalence of PD-L1–positive tumors, the clinical utility of PD-L1 expression in melanoma is not clear at this point, because unselected patients have such a high level of response," Dr. Daud said. Changes in T-cell subtype distribution as a pharmacodynamic marker "supports the proposed MK-3475 mechanism of action."

He characterized the study as "a good foundation to build on, and we think that ongoing studies looking at larger clinical trials will help clarify the role of PD-L1 expression in terms of correlating with response of patients treated with MK-3475. Clinical development of MK-3475, both as monotherapy and as part of combination strategies, is ongoing in multiple solid tumors and hematologic malignancies."

In the second study, Dr. Leena Gandhi presented extended data from an earlier trial of 38 patients with non–small cell lung cancer who were treated with MK-3475. That trial found that higher levels of PD-L1 expression "appeared to correlate with an increased response to MK-3475," Dr. Gandhi, a thoracic oncologist at the Dana-Farber Cancer Institute, Boston, said during a press briefing. The purpose of the current analysis, which included 146 patients, was to determine an optimal cut point for defining whether a tumor is likely to respond to MK-3475 therapy or not. The patients received the agent at three different doses: 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks. Tumors were assessed by imaging every 9 weeks and by RECIST 1.1 (Response Evaluation Criteria in Solid Tumors).

Dr. Gandhi and her associates found that PD-L1 levels of greater than 50% as measured by immunohistochemistry was the best cut-off point for determining whether a tumor is likely to respond to MK-3475. Six months after starting treatment, 41% of patients with tumors that contained high levels of PD-L1 prior to treatment had no disease progression, compared with 17% of those whose tumors contained low levels of PD-L1 (hazard ratio, 0.53; P = .004). This finding is "based on very small numbers of patients with long-term follow-up, so we expect that the final progression-free survival differences may change over time with additional patients," Dr. Gandhi noted.

As for overall survival, 72% of patients with tumors that contained high levels of PD-L1 were alive at 6 months, compared with 53% of those whose tumors contained low levels of PD-L1. This difference trended toward statistical significance (HR, 0.65; P = .134) and may also change as data from additional patients are realized, she said.

Dr. Gandhi noted that data from two ongoing studies will be used to "further explore the relationship between tumor PD-L1 expression and MK-3475 activity in NSCLC patients."

In an interview, Dr. Patricia M. LoRusso, director of the Center for Translational Therapeutics at Wayne State University’s Karmanos Cancer Institute, Detroit, characterized the MK-3475 biomarker as "maturing, but I still think it’s under investigation. I still think we have a ways to go in identifying the best predictive biomarker. I don’t think it’s 100% foolproof by any means."

Both studies were funded by Merck. Dr. Daud disclosed that he has served on the advisory board of Merck and GlaxoSmithKline. Dr. Gandhi said that she had no relevant financial conflicts to disclose.

Dr. LoRusso disclosed that she has received research funding from Agios Pharmaceuticals.

[email protected]

SAN DIEGO – Preliminary findings from two studies presented at the annual meeting of the American Association for Cancer Research suggest that cancer patients whose tumors contained the protein PD-L1 responded favorably to treatment with the investigational checkpoint inhibitor MK-3475.

A highly selective anti–PD-1 immunotherapy being developed by Merck, MK-3475 is designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein.

Both studies are analyses from the ongoing phase 1B KEYNOTE-001 study. In the first analysis, researchers led by Dr. Adil I. Daud evaluated tumor samples from 195 patients with late-stage melanoma who received MK-3475 at three different doses: 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 2 mg/kg every 3 weeks. Some of the patients had received prior treatment with ipilimumab.

Dr. Daud, codirector of the University of California, San Francisco, melanoma center and director of melanoma clinical research at the UCSF Helen Diller Family Comprehensive Cancer Center, and his associates measured the amount of PD-L1 in the tumor samples and considered them PD-L1 positive if at least 1 cell/100 tumors cells stained by immunohistochemistry contained the protein. They also used multiplex flow cytometry to assess absolute CD4 and CD8 T-cell counts and the percentage of activated CD4 and CD8 T-cell counts in peripheral blood.

All study participants had a new tumor biopsy within 2 months before the first dose of MK-3475. Their mean age was 63 years, 76% were male, and 76% had BRAF wild-type tumors. Of the 125 evaluable tumor samples, 89 (71%) were PD-L1 positive and 36 were PD-L1 negative. Disease did not progress for about 50 weeks among patients with PD-L1–positive tumors, compared with about 12 weeks among those with PD-L1–negative tumors. Among the entire study population, the overall response rate was 40%, "which is high for immunotherapy," Dr. Daud said during a press briefing.

Based on cut point of at least 1 cell/100 tumors cells, the response rate among patients with PD-L1–positive tumors was 49%, compared with 13% among patients with PD-L1–negative tumors (P = .0007). At 6 months, 57% of patients with PD-L1–positive tumors had no disease progression, compared with 35% of those whose tumors were PD-L1 negative (P = 0.0051).

Between baseline and week 6, the researchers observed a significant median increase in the percentage of CD8-positive CD4-positive T cells (14.6% vs. 15.7%, respectively) though no significant change in the absolute numbers of circulating T cells was observed.

"Given the high prevalence of PD-L1–positive tumors, the clinical utility of PD-L1 expression in melanoma is not clear at this point, because unselected patients have such a high level of response," Dr. Daud said. Changes in T-cell subtype distribution as a pharmacodynamic marker "supports the proposed MK-3475 mechanism of action."

He characterized the study as "a good foundation to build on, and we think that ongoing studies looking at larger clinical trials will help clarify the role of PD-L1 expression in terms of correlating with response of patients treated with MK-3475. Clinical development of MK-3475, both as monotherapy and as part of combination strategies, is ongoing in multiple solid tumors and hematologic malignancies."

In the second study, Dr. Leena Gandhi presented extended data from an earlier trial of 38 patients with non–small cell lung cancer who were treated with MK-3475. That trial found that higher levels of PD-L1 expression "appeared to correlate with an increased response to MK-3475," Dr. Gandhi, a thoracic oncologist at the Dana-Farber Cancer Institute, Boston, said during a press briefing. The purpose of the current analysis, which included 146 patients, was to determine an optimal cut point for defining whether a tumor is likely to respond to MK-3475 therapy or not. The patients received the agent at three different doses: 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks. Tumors were assessed by imaging every 9 weeks and by RECIST 1.1 (Response Evaluation Criteria in Solid Tumors).

Dr. Gandhi and her associates found that PD-L1 levels of greater than 50% as measured by immunohistochemistry was the best cut-off point for determining whether a tumor is likely to respond to MK-3475. Six months after starting treatment, 41% of patients with tumors that contained high levels of PD-L1 prior to treatment had no disease progression, compared with 17% of those whose tumors contained low levels of PD-L1 (hazard ratio, 0.53; P = .004). This finding is "based on very small numbers of patients with long-term follow-up, so we expect that the final progression-free survival differences may change over time with additional patients," Dr. Gandhi noted.

As for overall survival, 72% of patients with tumors that contained high levels of PD-L1 were alive at 6 months, compared with 53% of those whose tumors contained low levels of PD-L1. This difference trended toward statistical significance (HR, 0.65; P = .134) and may also change as data from additional patients are realized, she said.

Dr. Gandhi noted that data from two ongoing studies will be used to "further explore the relationship between tumor PD-L1 expression and MK-3475 activity in NSCLC patients."

In an interview, Dr. Patricia M. LoRusso, director of the Center for Translational Therapeutics at Wayne State University’s Karmanos Cancer Institute, Detroit, characterized the MK-3475 biomarker as "maturing, but I still think it’s under investigation. I still think we have a ways to go in identifying the best predictive biomarker. I don’t think it’s 100% foolproof by any means."

Both studies were funded by Merck. Dr. Daud disclosed that he has served on the advisory board of Merck and GlaxoSmithKline. Dr. Gandhi said that she had no relevant financial conflicts to disclose.

Dr. LoRusso disclosed that she has received research funding from Agios Pharmaceuticals.

[email protected]

Prostate tumorigenesis is related to sex hormones, particularly androgens. It also has been suggested that melanoma may be androgen dependent. Postulated mechanisms of pathogenesis include androgen level imbalance (for which early evidence may present as severe teenaged acne), chromosome telomere length alteration (for which increased risk for melanoma is associated with long telomeres), and host immune response modification.

In a December 2013 article published in the Journal of Clinical Oncology, Li et al (2013;31:4394-4399) confirmed that a personal history of prostate cancer was associated with an increased risk for subsequent melanoma. Among patients with prostate cancer whose median age at diagnosis was 68 years or younger, a higher hazard ratio of melanoma was noted. Also, similar to prostate cancer, they observed a positive association between melanoma risk and severe teenaged acne defined by the use of tetracycline for 4 or more years.

What’s the issue?

Are there clinical implications to the confirmation that there is an increased risk for patients with prostate cancer to subsequently develop melanoma? Specifically, should there be increased surveillance for melanoma in these individuals? Perhaps it would be reasonable to regularly perform a complete skin examination in all patients with a history of prostate cancer, especially men who had prostate cancer diagnosed before 68 years of age.

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

Prostate tumorigenesis is related to sex hormones, particularly androgens. It also has been suggested that melanoma may be androgen dependent. Postulated mechanisms of pathogenesis include androgen level imbalance (for which early evidence may present as severe teenaged acne), chromosome telomere length alteration (for which increased risk for melanoma is associated with long telomeres), and host immune response modification.

In a December 2013 article published in the Journal of Clinical Oncology, Li et al (2013;31:4394-4399) confirmed that a personal history of prostate cancer was associated with an increased risk for subsequent melanoma. Among patients with prostate cancer whose median age at diagnosis was 68 years or younger, a higher hazard ratio of melanoma was noted. Also, similar to prostate cancer, they observed a positive association between melanoma risk and severe teenaged acne defined by the use of tetracycline for 4 or more years.

What’s the issue?

Are there clinical implications to the confirmation that there is an increased risk for patients with prostate cancer to subsequently develop melanoma? Specifically, should there be increased surveillance for melanoma in these individuals? Perhaps it would be reasonable to regularly perform a complete skin examination in all patients with a history of prostate cancer, especially men who had prostate cancer diagnosed before 68 years of age.

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

Prostate tumorigenesis is related to sex hormones, particularly androgens. It also has been suggested that melanoma may be androgen dependent. Postulated mechanisms of pathogenesis include androgen level imbalance (for which early evidence may present as severe teenaged acne), chromosome telomere length alteration (for which increased risk for melanoma is associated with long telomeres), and host immune response modification.

In a December 2013 article published in the Journal of Clinical Oncology, Li et al (2013;31:4394-4399) confirmed that a personal history of prostate cancer was associated with an increased risk for subsequent melanoma. Among patients with prostate cancer whose median age at diagnosis was 68 years or younger, a higher hazard ratio of melanoma was noted. Also, similar to prostate cancer, they observed a positive association between melanoma risk and severe teenaged acne defined by the use of tetracycline for 4 or more years.

What’s the issue?

Are there clinical implications to the confirmation that there is an increased risk for patients with prostate cancer to subsequently develop melanoma? Specifically, should there be increased surveillance for melanoma in these individuals? Perhaps it would be reasonable to regularly perform a complete skin examination in all patients with a history of prostate cancer, especially men who had prostate cancer diagnosed before 68 years of age.

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