Melanoma

CHICAGO – Combining two approved therapies – GM-CSF and ipilimumab – extended overall survival rates by 35% and resulted in fewer grade 3-5 adverse events when compared with ipilimumab alone in a randomized study of 245 patients with metastatic melanoma.

At 1 year, the overall survival rate in the combination therapy group was 69%, with a median follow-up of nearly 18 months. At 1 year, survival in the ipilimumab-only group was 53% with a median follow-up of nearly 13 months, Dr. F. Stephen Hodi, Jr. reported at the annual meeting of the American Society of Clinical Oncology.

This is the first phase II trial to look at ipilimumab (Yervoy, Bristol-Myers Squibb) and the granulocyte macrophage colony-stimulating factor (GM-CSF) sargramostim (Leukine, Sanofi) in combination in any cancer, said Dr. Hodi, the principal investigator for the trial, which was conducted by the ECOG-ACRIN Cancer Research Group (formerly the Eastern Cooperative Oncology Group) trial. In this study, ipilimumab was used at a dose of 10 mg/kg, which is higher than the FDA-approved dose of 3 mg/kg.

"We are waiting for the data to mature in ongoing studies examining the relative efficacy of 3 mg/kg and 10 mg/kg dosing," said Dr. Hodi, director of the melanoma center at Dana-Farber Cancer Institute in Boston.

The results in the current trial are another indication of the impact that immunotherapy can have for patients with advanced melanoma. Since both GM-CSF and ipilimumab are commercially available, oncologists need to determine the best way to apply these findings in everyday practice. The next step will then be to define the role of GM-CSF in combination with other immune checkpoint targeting drugs, such as therapies that target the PD-1 and PD-L1 pathway, he said.

"We have been using GM-CSF in melanoma as a stand-alone therapy," Dr. Lynn M. Schuchter, the C. Willard Robinson Professor of Hematology-Oncology at the University of Pennsylvania, Philadelphia, and an expert on melanoma, said at a press conference where the study results were announced. "It will be interesting to see if payers will cover this (combination treatment)."

Ipilimumab targets CTLA-4, a protein that keeps immune T-cells in an inactive state. GM-CSF is a growth factor commonly used to boost white blood cell counts after chemotherapy or stem cell transplantation.

For this study, 245 patients were randomized to receive ipilimumab plus GM-CSF or ipilimumab alone. All study participants were in otherwise good health, with an ECOG performance status of 0-1 and adequate end-organ function, no autoimmune disease, and no prior use of CTLA-4 blockade or CD137 agonists. All had radiographically measurable metastatic melanoma, but with no CNS metastases, and had received up to one prior treatment over 4 weeks before starting in the trial.

The 123 patients randomized to the combination therapy were given sargramostim at 250 micrograms injected subcutaneously on day 1-14 of a 21 day cycle. For induction therapy, ipilimumab was given at a dose of 10 mg/kg intravenously once every 3 weeks for four cycles as induction therapy and once every 12 weeks as maintenance therapy. The 122 patients randomized to ipilimumab alone received the drug on the same schedule.

In both study arms, tumor shrinkage rates were comparable at 11% and 14%, and progression-free survival was similar at about 3 months. But the overall survival rate was longer in the combination treatment arm. One year after the start of therapy and with a median follow-up of 13.3 months, 69% of patients given the combination therapy and 53% of those who got ipilimumab alone were still alive, for a 35% lower risk of death with the combination therapy (hazard ratio, 0.64; P = .014).

Additionally, the combination treatment was associated with fewer serious side effects, compared with ipilimumab alone. The most significant differences were in lung and gastrointestinal toxicities.

Grade 3-5 adverse events occurred in 45% of patients given the combination therapy and in 57% given ipilimumab alone (p2 = 0.078). There were two possible treatment-related deaths in the combination arm (one colonic perforation and one cardiac arrest) and 7 possible treatment-related deaths in the ipilimumab-only arm: (two cases of multi-organ failure, two colonic perforations, one case of liver failure, and two cases of respiratory failure).

The research was supported in part by the National Cancer Institute (Cancer Therapy Evaluation Program), Sanofi, and Bristol-Myers Squibb. Dr. Hodi disclosed receiving research funding and a being a consultant or in an advisory role with Bristol-Myers Squibb.

CHICAGO – Combining two approved therapies – GM-CSF and ipilimumab – extended overall survival rates by 35% and resulted in fewer grade 3-5 adverse events when compared with ipilimumab alone in a randomized study of 245 patients with metastatic melanoma.

At 1 year, the overall survival rate in the combination therapy group was 69%, with a median follow-up of nearly 18 months. At 1 year, survival in the ipilimumab-only group was 53% with a median follow-up of nearly 13 months, Dr. F. Stephen Hodi, Jr. reported at the annual meeting of the American Society of Clinical Oncology.

This is the first phase II trial to look at ipilimumab (Yervoy, Bristol-Myers Squibb) and the granulocyte macrophage colony-stimulating factor (GM-CSF) sargramostim (Leukine, Sanofi) in combination in any cancer, said Dr. Hodi, the principal investigator for the trial, which was conducted by the ECOG-ACRIN Cancer Research Group (formerly the Eastern Cooperative Oncology Group) trial. In this study, ipilimumab was used at a dose of 10 mg/kg, which is higher than the FDA-approved dose of 3 mg/kg.

"We are waiting for the data to mature in ongoing studies examining the relative efficacy of 3 mg/kg and 10 mg/kg dosing," said Dr. Hodi, director of the melanoma center at Dana-Farber Cancer Institute in Boston.

The results in the current trial are another indication of the impact that immunotherapy can have for patients with advanced melanoma. Since both GM-CSF and ipilimumab are commercially available, oncologists need to determine the best way to apply these findings in everyday practice. The next step will then be to define the role of GM-CSF in combination with other immune checkpoint targeting drugs, such as therapies that target the PD-1 and PD-L1 pathway, he said.

"We have been using GM-CSF in melanoma as a stand-alone therapy," Dr. Lynn M. Schuchter, the C. Willard Robinson Professor of Hematology-Oncology at the University of Pennsylvania, Philadelphia, and an expert on melanoma, said at a press conference where the study results were announced. "It will be interesting to see if payers will cover this (combination treatment)."

Ipilimumab targets CTLA-4, a protein that keeps immune T-cells in an inactive state. GM-CSF is a growth factor commonly used to boost white blood cell counts after chemotherapy or stem cell transplantation.

For this study, 245 patients were randomized to receive ipilimumab plus GM-CSF or ipilimumab alone. All study participants were in otherwise good health, with an ECOG performance status of 0-1 and adequate end-organ function, no autoimmune disease, and no prior use of CTLA-4 blockade or CD137 agonists. All had radiographically measurable metastatic melanoma, but with no CNS metastases, and had received up to one prior treatment over 4 weeks before starting in the trial.

The 123 patients randomized to the combination therapy were given sargramostim at 250 micrograms injected subcutaneously on day 1-14 of a 21 day cycle. For induction therapy, ipilimumab was given at a dose of 10 mg/kg intravenously once every 3 weeks for four cycles as induction therapy and once every 12 weeks as maintenance therapy. The 122 patients randomized to ipilimumab alone received the drug on the same schedule.

In both study arms, tumor shrinkage rates were comparable at 11% and 14%, and progression-free survival was similar at about 3 months. But the overall survival rate was longer in the combination treatment arm. One year after the start of therapy and with a median follow-up of 13.3 months, 69% of patients given the combination therapy and 53% of those who got ipilimumab alone were still alive, for a 35% lower risk of death with the combination therapy (hazard ratio, 0.64; P = .014).

Additionally, the combination treatment was associated with fewer serious side effects, compared with ipilimumab alone. The most significant differences were in lung and gastrointestinal toxicities.

Grade 3-5 adverse events occurred in 45% of patients given the combination therapy and in 57% given ipilimumab alone (p2 = 0.078). There were two possible treatment-related deaths in the combination arm (one colonic perforation and one cardiac arrest) and 7 possible treatment-related deaths in the ipilimumab-only arm: (two cases of multi-organ failure, two colonic perforations, one case of liver failure, and two cases of respiratory failure).

The research was supported in part by the National Cancer Institute (Cancer Therapy Evaluation Program), Sanofi, and Bristol-Myers Squibb. Dr. Hodi disclosed receiving research funding and a being a consultant or in an advisory role with Bristol-Myers Squibb.

CHICAGO – Combining two approved therapies – GM-CSF and ipilimumab – extended overall survival rates by 35% and resulted in fewer grade 3-5 adverse events when compared with ipilimumab alone in a randomized study of 245 patients with metastatic melanoma.

At 1 year, the overall survival rate in the combination therapy group was 69%, with a median follow-up of nearly 18 months. At 1 year, survival in the ipilimumab-only group was 53% with a median follow-up of nearly 13 months, Dr. F. Stephen Hodi, Jr. reported at the annual meeting of the American Society of Clinical Oncology.

This is the first phase II trial to look at ipilimumab (Yervoy, Bristol-Myers Squibb) and the granulocyte macrophage colony-stimulating factor (GM-CSF) sargramostim (Leukine, Sanofi) in combination in any cancer, said Dr. Hodi, the principal investigator for the trial, which was conducted by the ECOG-ACRIN Cancer Research Group (formerly the Eastern Cooperative Oncology Group) trial. In this study, ipilimumab was used at a dose of 10 mg/kg, which is higher than the FDA-approved dose of 3 mg/kg.

"We are waiting for the data to mature in ongoing studies examining the relative efficacy of 3 mg/kg and 10 mg/kg dosing," said Dr. Hodi, director of the melanoma center at Dana-Farber Cancer Institute in Boston.

The results in the current trial are another indication of the impact that immunotherapy can have for patients with advanced melanoma. Since both GM-CSF and ipilimumab are commercially available, oncologists need to determine the best way to apply these findings in everyday practice. The next step will then be to define the role of GM-CSF in combination with other immune checkpoint targeting drugs, such as therapies that target the PD-1 and PD-L1 pathway, he said.

"We have been using GM-CSF in melanoma as a stand-alone therapy," Dr. Lynn M. Schuchter, the C. Willard Robinson Professor of Hematology-Oncology at the University of Pennsylvania, Philadelphia, and an expert on melanoma, said at a press conference where the study results were announced. "It will be interesting to see if payers will cover this (combination treatment)."

Ipilimumab targets CTLA-4, a protein that keeps immune T-cells in an inactive state. GM-CSF is a growth factor commonly used to boost white blood cell counts after chemotherapy or stem cell transplantation.

For this study, 245 patients were randomized to receive ipilimumab plus GM-CSF or ipilimumab alone. All study participants were in otherwise good health, with an ECOG performance status of 0-1 and adequate end-organ function, no autoimmune disease, and no prior use of CTLA-4 blockade or CD137 agonists. All had radiographically measurable metastatic melanoma, but with no CNS metastases, and had received up to one prior treatment over 4 weeks before starting in the trial.

The 123 patients randomized to the combination therapy were given sargramostim at 250 micrograms injected subcutaneously on day 1-14 of a 21 day cycle. For induction therapy, ipilimumab was given at a dose of 10 mg/kg intravenously once every 3 weeks for four cycles as induction therapy and once every 12 weeks as maintenance therapy. The 122 patients randomized to ipilimumab alone received the drug on the same schedule.

In both study arms, tumor shrinkage rates were comparable at 11% and 14%, and progression-free survival was similar at about 3 months. But the overall survival rate was longer in the combination treatment arm. One year after the start of therapy and with a median follow-up of 13.3 months, 69% of patients given the combination therapy and 53% of those who got ipilimumab alone were still alive, for a 35% lower risk of death with the combination therapy (hazard ratio, 0.64; P = .014).

Additionally, the combination treatment was associated with fewer serious side effects, compared with ipilimumab alone. The most significant differences were in lung and gastrointestinal toxicities.

Grade 3-5 adverse events occurred in 45% of patients given the combination therapy and in 57% given ipilimumab alone (p2 = 0.078). There were two possible treatment-related deaths in the combination arm (one colonic perforation and one cardiac arrest) and 7 possible treatment-related deaths in the ipilimumab-only arm: (two cases of multi-organ failure, two colonic perforations, one case of liver failure, and two cases of respiratory failure).

The research was supported in part by the National Cancer Institute (Cancer Therapy Evaluation Program), Sanofi, and Bristol-Myers Squibb. Dr. Hodi disclosed receiving research funding and a being a consultant or in an advisory role with Bristol-Myers Squibb.

CHICAGO – With new targeted therapies and immunotherapies for metastatic melanoma, chemotherapy is now a thirdtier option for these patients, according to melanoma expert Dr. Lynn M. Schuchter, of the University of Pennsylvania, Philadelphia.

Dr. Schuchter discusses new practice-changing approaches in the treatment of melanoma in an interview at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – With new targeted therapies and immunotherapies for metastatic melanoma, chemotherapy is now a thirdtier option for these patients, according to melanoma expert Dr. Lynn M. Schuchter, of the University of Pennsylvania, Philadelphia.

Dr. Schuchter discusses new practice-changing approaches in the treatment of melanoma in an interview at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – With new targeted therapies and immunotherapies for metastatic melanoma, chemotherapy is now a thirdtier option for these patients, according to melanoma expert Dr. Lynn M. Schuchter, of the University of Pennsylvania, Philadelphia.

Dr. Schuchter discusses new practice-changing approaches in the treatment of melanoma in an interview at the annual meeting of the American Society of Clinical Oncology.

Cutaneous squamous cell carcinoma (SCC) is the second most common nonmelanoma skin cancer. The clinical features of SCC typically include scaly, crusted, nonhealing, ulcerative lesions in sun-exposed areas of the body. We present here the interesting case of a patient who was diagnosed with extremely severe SCC, keratoacanthoma-type (KA; SCC-KA type) with multiple annular, crusted, papular lesions (8-20 mm) on the dorsal aspect of his hands and forearms. The patient was successfully treated with cetuximab over 78 days, with complete resolution.

*Click on the link to the left for a PDF of the full article.

Cutaneous squamous cell carcinoma (SCC) is the second most common nonmelanoma skin cancer. The clinical features of SCC typically include scaly, crusted, nonhealing, ulcerative lesions in sun-exposed areas of the body. We present here the interesting case of a patient who was diagnosed with extremely severe SCC, keratoacanthoma-type (KA; SCC-KA type) with multiple annular, crusted, papular lesions (8-20 mm) on the dorsal aspect of his hands and forearms. The patient was successfully treated with cetuximab over 78 days, with complete resolution.

*Click on the link to the left for a PDF of the full article.

Cutaneous squamous cell carcinoma (SCC) is the second most common nonmelanoma skin cancer. The clinical features of SCC typically include scaly, crusted, nonhealing, ulcerative lesions in sun-exposed areas of the body. We present here the interesting case of a patient who was diagnosed with extremely severe SCC, keratoacanthoma-type (KA; SCC-KA type) with multiple annular, crusted, papular lesions (8-20 mm) on the dorsal aspect of his hands and forearms. The patient was successfully treated with cetuximab over 78 days, with complete resolution.

*Click on the link to the left for a PDF of the full article.

Two drugs that target mutations on the BRAF gene have been approved for treating metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations, the Food and Drug Administration announced on May 29.

Dabrafenib and trametinib are the third and fourth drugs to be approved by the FDA for metastatic or unresectable melanoma since 2011, when vemurafenib (Zelboraf) and ipilimumab (Yervoy) were approved.

Dabrafenib, a BRAF inhibitor, was approved for patients with unresectable or metastatic melanoma with the BRAF V600E mutation as detected by an FDA-approved test. It will be marketed as Tafinlar and is taken twice a day, by mouth.

Trametinib, a MEK inhibitor, was approved to treat patients with unresectable or metastatic melanomas that express the BRAF V600E or V600K mutations, as detected by the test. It will be marketed as Mekinist, and is taken by mouth once a day.

The two drugs are not approved as combination treatment, according to a statement from the FDA.

The just-approved THxID BRAF test will be used to determine if the mutations are present. About half of melanomas have a BRAF mutation, according to the FDA.

"Advancements in our understanding of the biological pathways of a disease have allowed for the development" of these two drugs, Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research (CDER), said in the statement. The approval of the drugs and the diagnostic test, the second that tests for the BRAF mutation, "demonstrates the commitment of pharmaceutical and diagnostic partners to develop products that detect and target the molecular drivers of cancer," added Alberto Gutierrez, Ph.D., director of the CDER Office of In Vitro Diagnostic Devices and Radiological Health.

In a study of 250 people with previously untreated BRAF V600E mutation–positive, unresectable or metastatic melanoma, the median progression-free survival (PFS) was 5.1 months among those randomized to treatment with dabrafenib vs. 2.7 months among those randomized to chemotherapy with dacarbazine, a statistically significant difference (hazard ratio, 0.33).

The most common adverse events associated with dabrafenib were hyperkeratosis, headache, fever, joint pain, noncancerous skin tumors, alopecia, and hand-foot syndrome. The most serious adverse events associated with dabrafenib treatment were an increased risk of cutaneous squamous cell carcinoma, fevers complicated by hypotension, severe rigors, dehydration, kidney failure, and hyperglycemia requiring an increased dose or initiation of treatment with glucose-lowering drugs, according to the FDA.

In a study of 322 patients with metastatic or unresectable melanoma positive for the BRAF V600E or V600K mutation, the median PFS was 4.8 months among those on trametinib vs. 1.5 months among those on chemotherapy (paclitaxel or dacarbazine), a significant difference (HR, 0.47). Those patients who had been treated with dabrafenib or another BRAF inhibitor "did not appear to benefit" from trametinib treatment, according to the FDA.

Rash, diarrhea, peripheral edema, and acneiform skin breakouts were the most common adverse effects associated with trametinib. Among the most serious adverse events associated with trametinib were heart failure, lung inflammation, skin infections, and loss of vision.

The labels for both drugs warn that the drugs can cause fetal harm.

Dabrafenib and trametinib are marketed by GlaxoSmithKline (GSK), and the THxID BRAF Kit is manufactured by bioMérieux, a French company.

The two drugs are expected to be available no later than the "early third quarter" of 2013, according to a GSK statement. The company worked with bioMérieux to develop the test, and it is the only FDA-approved test that detects the V600K mutation.

Serious adverse events associated with these drugs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

[email protected]

Two drugs that target mutations on the BRAF gene have been approved for treating metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations, the Food and Drug Administration announced on May 29.

Dabrafenib and trametinib are the third and fourth drugs to be approved by the FDA for metastatic or unresectable melanoma since 2011, when vemurafenib (Zelboraf) and ipilimumab (Yervoy) were approved.

Dabrafenib, a BRAF inhibitor, was approved for patients with unresectable or metastatic melanoma with the BRAF V600E mutation as detected by an FDA-approved test. It will be marketed as Tafinlar and is taken twice a day, by mouth.

Trametinib, a MEK inhibitor, was approved to treat patients with unresectable or metastatic melanomas that express the BRAF V600E or V600K mutations, as detected by the test. It will be marketed as Mekinist, and is taken by mouth once a day.

The two drugs are not approved as combination treatment, according to a statement from the FDA.

The just-approved THxID BRAF test will be used to determine if the mutations are present. About half of melanomas have a BRAF mutation, according to the FDA.

"Advancements in our understanding of the biological pathways of a disease have allowed for the development" of these two drugs, Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research (CDER), said in the statement. The approval of the drugs and the diagnostic test, the second that tests for the BRAF mutation, "demonstrates the commitment of pharmaceutical and diagnostic partners to develop products that detect and target the molecular drivers of cancer," added Alberto Gutierrez, Ph.D., director of the CDER Office of In Vitro Diagnostic Devices and Radiological Health.

In a study of 250 people with previously untreated BRAF V600E mutation–positive, unresectable or metastatic melanoma, the median progression-free survival (PFS) was 5.1 months among those randomized to treatment with dabrafenib vs. 2.7 months among those randomized to chemotherapy with dacarbazine, a statistically significant difference (hazard ratio, 0.33).

The most common adverse events associated with dabrafenib were hyperkeratosis, headache, fever, joint pain, noncancerous skin tumors, alopecia, and hand-foot syndrome. The most serious adverse events associated with dabrafenib treatment were an increased risk of cutaneous squamous cell carcinoma, fevers complicated by hypotension, severe rigors, dehydration, kidney failure, and hyperglycemia requiring an increased dose or initiation of treatment with glucose-lowering drugs, according to the FDA.

In a study of 322 patients with metastatic or unresectable melanoma positive for the BRAF V600E or V600K mutation, the median PFS was 4.8 months among those on trametinib vs. 1.5 months among those on chemotherapy (paclitaxel or dacarbazine), a significant difference (HR, 0.47). Those patients who had been treated with dabrafenib or another BRAF inhibitor "did not appear to benefit" from trametinib treatment, according to the FDA.

Rash, diarrhea, peripheral edema, and acneiform skin breakouts were the most common adverse effects associated with trametinib. Among the most serious adverse events associated with trametinib were heart failure, lung inflammation, skin infections, and loss of vision.

The labels for both drugs warn that the drugs can cause fetal harm.

Dabrafenib and trametinib are marketed by GlaxoSmithKline (GSK), and the THxID BRAF Kit is manufactured by bioMérieux, a French company.

The two drugs are expected to be available no later than the "early third quarter" of 2013, according to a GSK statement. The company worked with bioMérieux to develop the test, and it is the only FDA-approved test that detects the V600K mutation.

Serious adverse events associated with these drugs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

[email protected]

Two drugs that target mutations on the BRAF gene have been approved for treating metastatic or unresectable melanomas that express the mutations – along with a companion test to detect the mutations, the Food and Drug Administration announced on May 29.

Dabrafenib and trametinib are the third and fourth drugs to be approved by the FDA for metastatic or unresectable melanoma since 2011, when vemurafenib (Zelboraf) and ipilimumab (Yervoy) were approved.

Dabrafenib, a BRAF inhibitor, was approved for patients with unresectable or metastatic melanoma with the BRAF V600E mutation as detected by an FDA-approved test. It will be marketed as Tafinlar and is taken twice a day, by mouth.

Trametinib, a MEK inhibitor, was approved to treat patients with unresectable or metastatic melanomas that express the BRAF V600E or V600K mutations, as detected by the test. It will be marketed as Mekinist, and is taken by mouth once a day.

The two drugs are not approved as combination treatment, according to a statement from the FDA.

The just-approved THxID BRAF test will be used to determine if the mutations are present. About half of melanomas have a BRAF mutation, according to the FDA.

"Advancements in our understanding of the biological pathways of a disease have allowed for the development" of these two drugs, Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research (CDER), said in the statement. The approval of the drugs and the diagnostic test, the second that tests for the BRAF mutation, "demonstrates the commitment of pharmaceutical and diagnostic partners to develop products that detect and target the molecular drivers of cancer," added Alberto Gutierrez, Ph.D., director of the CDER Office of In Vitro Diagnostic Devices and Radiological Health.

In a study of 250 people with previously untreated BRAF V600E mutation–positive, unresectable or metastatic melanoma, the median progression-free survival (PFS) was 5.1 months among those randomized to treatment with dabrafenib vs. 2.7 months among those randomized to chemotherapy with dacarbazine, a statistically significant difference (hazard ratio, 0.33).

The most common adverse events associated with dabrafenib were hyperkeratosis, headache, fever, joint pain, noncancerous skin tumors, alopecia, and hand-foot syndrome. The most serious adverse events associated with dabrafenib treatment were an increased risk of cutaneous squamous cell carcinoma, fevers complicated by hypotension, severe rigors, dehydration, kidney failure, and hyperglycemia requiring an increased dose or initiation of treatment with glucose-lowering drugs, according to the FDA.

In a study of 322 patients with metastatic or unresectable melanoma positive for the BRAF V600E or V600K mutation, the median PFS was 4.8 months among those on trametinib vs. 1.5 months among those on chemotherapy (paclitaxel or dacarbazine), a significant difference (HR, 0.47). Those patients who had been treated with dabrafenib or another BRAF inhibitor "did not appear to benefit" from trametinib treatment, according to the FDA.

Rash, diarrhea, peripheral edema, and acneiform skin breakouts were the most common adverse effects associated with trametinib. Among the most serious adverse events associated with trametinib were heart failure, lung inflammation, skin infections, and loss of vision.

The labels for both drugs warn that the drugs can cause fetal harm.

Dabrafenib and trametinib are marketed by GlaxoSmithKline (GSK), and the THxID BRAF Kit is manufactured by bioMérieux, a French company.

The two drugs are expected to be available no later than the "early third quarter" of 2013, according to a GSK statement. The company worked with bioMérieux to develop the test, and it is the only FDA-approved test that detects the V600K mutation.

Serious adverse events associated with these drugs should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch/.

[email protected]

BOSTON – Fractional laser-assisted photodynamic therapy can effectively treat actinic keratoses in organ transplant recipients, but at a cost of more intense postoperative skin reactions than with laser therapy alone, based on data from a randomized clinical trial.

Intensified ablative fractional laser-assisted photodynamic therapy (AFXL-PDT) was significantly more effective at clearing actinic keratoses (AKs) and warty lesions on the dorsal aspect of the hands of organ transplant recipients than AFXL alone, reported Dr. Merete Haedersdal of the University of Copenhagen and a visiting scientist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston.

The treatment was painful, and 3 of 10 patients reported intense inflammation a week afterward, Dr. Haedersdal noted.

However, "this new treatment modality also works well for immunosuppressed patients, and I do think it works very well for immunosuppressed patients with multiple AKs," she said at the annual meeting of the American Society for Laser Medicine and Surgery.

High-risk population

Organ transplant recipients are at a 100-fold or greater risk for developing squamous cell carcinomas, which can arise from AKs, because of their chronic immunosuppressive treatment regimens. Cancers that develop in these patients tend to be quite aggressive, with a high rate of metastases and an attributable morality rate of 6%-8%, said Dr. Haedersdal.

"Therefore, there is a huge motivation to come up with intensified treatment regimens for these patients," she said.

PDT is a well-established therapy in transplant recipients, but it is less effective in these patients than in patients with intact immune responses. It is also less effective for thick lesions or lesions on the extremities.

Dr. Haedersdal and her colleagues previously demonstrated the efficacy of AFXL-PDT for treating AKs with a carbon dioxide laser in immunocompetent patients. In the current study, they compared the therapy with ablative fractional CO₂ laser alone in 10 organ transplant recipients with a total of 680 AKs and 409 wartlike lesions on the dorsal hands, and a collective history of 21 previous squamous cell carcinomas.

In a randomized intrapatient trial, the participants first underwent targeted ablation of localized keratotic lesions, and then were randomly assigned to receive one field treatment with AFXL-PDT on one hand, and AFXL alone on the other.

For AFXL, energy was delivered with the laser set to 30 W, a 0.12-mm spot size, a 1.32- to 2.06-millisecond pulse duration, and 40-60 mJ with the target of 4.3%-5.2% coverage; settings were based on the severity of skin atrophy.

After laser exposure, lesions randomized to receive PDT were treated with methyl aminolevulinate applied under occlusion for 3 hours, and were then exposed to red diode light at 37 J/cm².

‘Really impressive’ cure rate

The combined modality completely cleared 73% of all AKs, compared with 31% cleared by AFXL alone (P = .002), and 37% of all wartlike lesions, compared with 14% for AFXL (P = .02) at 4 months’ follow-up. The patients were clinically assessed by raters blinded to treatment type.

"Normally, when we deliver PDT for these patients, we have – from just a single treatment – cure rates on the acral lesions of about 30%-40%, so this was really impressive to get a complete cure rate for AKs at a level of 73%," Dr. Haedersdal said.

Overall, AKs treated with AFXL-PDT were rated as improved by a median of 83%, 15% as unchanged, and 3% as worsened, compared with AFXL-only rates of 52%, 47%, and 4%, respectively.

Thinner AKs responded better to treatment than thick lesions, with an odds ratio (OR) for grade 2 vs. grade 1 lesions of 0.34 (P = .001) and an OR for grade 3 vs. grade 1 of 0.21 (P = .001).

Safety data showed that AFXL treatment was generally not painful, with a mean visual analog scale (VAS) pain score of 1, and the PDT was more painful, with a mean VAS of 4.5 during LED illumination. Seven of 10 patients requested anesthesia during the procedure, Dr. Haedersdal noted.

In addition, at 1 week post treatment, 3 of 10 patients reported intense inflammation of the treated sites, 3 had pigment changes with AFXL-PDT, and 1 had a pigment change with AFXL alone.

The take-home message, Dr. Haedersdal said, is: "Do not deliver laser-assisted PDT to large areas; you have to deliver it to refined areas."

However, eight patients gave a favorable overall assessment to the combined treatments, and the remaining two rated the combined therapy and laser-only therapy as being equally effective.

The study was supported by a research grant to Dr. Haedersdal from Galderma. She also disclosed serving on a Galderma advisory board.

BOSTON – Fractional laser-assisted photodynamic therapy can effectively treat actinic keratoses in organ transplant recipients, but at a cost of more intense postoperative skin reactions than with laser therapy alone, based on data from a randomized clinical trial.

Intensified ablative fractional laser-assisted photodynamic therapy (AFXL-PDT) was significantly more effective at clearing actinic keratoses (AKs) and warty lesions on the dorsal aspect of the hands of organ transplant recipients than AFXL alone, reported Dr. Merete Haedersdal of the University of Copenhagen and a visiting scientist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston.

The treatment was painful, and 3 of 10 patients reported intense inflammation a week afterward, Dr. Haedersdal noted.

However, "this new treatment modality also works well for immunosuppressed patients, and I do think it works very well for immunosuppressed patients with multiple AKs," she said at the annual meeting of the American Society for Laser Medicine and Surgery.

High-risk population

Organ transplant recipients are at a 100-fold or greater risk for developing squamous cell carcinomas, which can arise from AKs, because of their chronic immunosuppressive treatment regimens. Cancers that develop in these patients tend to be quite aggressive, with a high rate of metastases and an attributable morality rate of 6%-8%, said Dr. Haedersdal.

"Therefore, there is a huge motivation to come up with intensified treatment regimens for these patients," she said.

PDT is a well-established therapy in transplant recipients, but it is less effective in these patients than in patients with intact immune responses. It is also less effective for thick lesions or lesions on the extremities.

Dr. Haedersdal and her colleagues previously demonstrated the efficacy of AFXL-PDT for treating AKs with a carbon dioxide laser in immunocompetent patients. In the current study, they compared the therapy with ablative fractional CO₂ laser alone in 10 organ transplant recipients with a total of 680 AKs and 409 wartlike lesions on the dorsal hands, and a collective history of 21 previous squamous cell carcinomas.

In a randomized intrapatient trial, the participants first underwent targeted ablation of localized keratotic lesions, and then were randomly assigned to receive one field treatment with AFXL-PDT on one hand, and AFXL alone on the other.

For AFXL, energy was delivered with the laser set to 30 W, a 0.12-mm spot size, a 1.32- to 2.06-millisecond pulse duration, and 40-60 mJ with the target of 4.3%-5.2% coverage; settings were based on the severity of skin atrophy.

After laser exposure, lesions randomized to receive PDT were treated with methyl aminolevulinate applied under occlusion for 3 hours, and were then exposed to red diode light at 37 J/cm².

‘Really impressive’ cure rate

The combined modality completely cleared 73% of all AKs, compared with 31% cleared by AFXL alone (P = .002), and 37% of all wartlike lesions, compared with 14% for AFXL (P = .02) at 4 months’ follow-up. The patients were clinically assessed by raters blinded to treatment type.

"Normally, when we deliver PDT for these patients, we have – from just a single treatment – cure rates on the acral lesions of about 30%-40%, so this was really impressive to get a complete cure rate for AKs at a level of 73%," Dr. Haedersdal said.

Overall, AKs treated with AFXL-PDT were rated as improved by a median of 83%, 15% as unchanged, and 3% as worsened, compared with AFXL-only rates of 52%, 47%, and 4%, respectively.

Thinner AKs responded better to treatment than thick lesions, with an odds ratio (OR) for grade 2 vs. grade 1 lesions of 0.34 (P = .001) and an OR for grade 3 vs. grade 1 of 0.21 (P = .001).

Safety data showed that AFXL treatment was generally not painful, with a mean visual analog scale (VAS) pain score of 1, and the PDT was more painful, with a mean VAS of 4.5 during LED illumination. Seven of 10 patients requested anesthesia during the procedure, Dr. Haedersdal noted.

In addition, at 1 week post treatment, 3 of 10 patients reported intense inflammation of the treated sites, 3 had pigment changes with AFXL-PDT, and 1 had a pigment change with AFXL alone.

The take-home message, Dr. Haedersdal said, is: "Do not deliver laser-assisted PDT to large areas; you have to deliver it to refined areas."

However, eight patients gave a favorable overall assessment to the combined treatments, and the remaining two rated the combined therapy and laser-only therapy as being equally effective.

The study was supported by a research grant to Dr. Haedersdal from Galderma. She also disclosed serving on a Galderma advisory board.

BOSTON – Fractional laser-assisted photodynamic therapy can effectively treat actinic keratoses in organ transplant recipients, but at a cost of more intense postoperative skin reactions than with laser therapy alone, based on data from a randomized clinical trial.

Intensified ablative fractional laser-assisted photodynamic therapy (AFXL-PDT) was significantly more effective at clearing actinic keratoses (AKs) and warty lesions on the dorsal aspect of the hands of organ transplant recipients than AFXL alone, reported Dr. Merete Haedersdal of the University of Copenhagen and a visiting scientist at the Wellman Center for Photomedicine at Massachusetts General Hospital, Boston.

The treatment was painful, and 3 of 10 patients reported intense inflammation a week afterward, Dr. Haedersdal noted.

However, "this new treatment modality also works well for immunosuppressed patients, and I do think it works very well for immunosuppressed patients with multiple AKs," she said at the annual meeting of the American Society for Laser Medicine and Surgery.

High-risk population

Organ transplant recipients are at a 100-fold or greater risk for developing squamous cell carcinomas, which can arise from AKs, because of their chronic immunosuppressive treatment regimens. Cancers that develop in these patients tend to be quite aggressive, with a high rate of metastases and an attributable morality rate of 6%-8%, said Dr. Haedersdal.

"Therefore, there is a huge motivation to come up with intensified treatment regimens for these patients," she said.

PDT is a well-established therapy in transplant recipients, but it is less effective in these patients than in patients with intact immune responses. It is also less effective for thick lesions or lesions on the extremities.

Dr. Haedersdal and her colleagues previously demonstrated the efficacy of AFXL-PDT for treating AKs with a carbon dioxide laser in immunocompetent patients. In the current study, they compared the therapy with ablative fractional CO₂ laser alone in 10 organ transplant recipients with a total of 680 AKs and 409 wartlike lesions on the dorsal hands, and a collective history of 21 previous squamous cell carcinomas.

In a randomized intrapatient trial, the participants first underwent targeted ablation of localized keratotic lesions, and then were randomly assigned to receive one field treatment with AFXL-PDT on one hand, and AFXL alone on the other.

For AFXL, energy was delivered with the laser set to 30 W, a 0.12-mm spot size, a 1.32- to 2.06-millisecond pulse duration, and 40-60 mJ with the target of 4.3%-5.2% coverage; settings were based on the severity of skin atrophy.

After laser exposure, lesions randomized to receive PDT were treated with methyl aminolevulinate applied under occlusion for 3 hours, and were then exposed to red diode light at 37 J/cm².

‘Really impressive’ cure rate

The combined modality completely cleared 73% of all AKs, compared with 31% cleared by AFXL alone (P = .002), and 37% of all wartlike lesions, compared with 14% for AFXL (P = .02) at 4 months’ follow-up. The patients were clinically assessed by raters blinded to treatment type.

"Normally, when we deliver PDT for these patients, we have – from just a single treatment – cure rates on the acral lesions of about 30%-40%, so this was really impressive to get a complete cure rate for AKs at a level of 73%," Dr. Haedersdal said.

Overall, AKs treated with AFXL-PDT were rated as improved by a median of 83%, 15% as unchanged, and 3% as worsened, compared with AFXL-only rates of 52%, 47%, and 4%, respectively.

Thinner AKs responded better to treatment than thick lesions, with an odds ratio (OR) for grade 2 vs. grade 1 lesions of 0.34 (P = .001) and an OR for grade 3 vs. grade 1 of 0.21 (P = .001).

Safety data showed that AFXL treatment was generally not painful, with a mean visual analog scale (VAS) pain score of 1, and the PDT was more painful, with a mean VAS of 4.5 during LED illumination. Seven of 10 patients requested anesthesia during the procedure, Dr. Haedersdal noted.

In addition, at 1 week post treatment, 3 of 10 patients reported intense inflammation of the treated sites, 3 had pigment changes with AFXL-PDT, and 1 had a pigment change with AFXL alone.

The take-home message, Dr. Haedersdal said, is: "Do not deliver laser-assisted PDT to large areas; you have to deliver it to refined areas."

However, eight patients gave a favorable overall assessment to the combined treatments, and the remaining two rated the combined therapy and laser-only therapy as being equally effective.

The study was supported by a research grant to Dr. Haedersdal from Galderma. She also disclosed serving on a Galderma advisory board.

How do you advise your patients about sunscreen? Some fodder for discussion (or possibly more confusion) comes from the Environmental Working Group, which has released its annual list of which sunscreens it deems both safe and effective – according to its criteria.

The Environmental Working Group (EWG), a nonprofit environmental health research and advocacy organization based in Washington, has issued the list for the past 7 years, just before Memorial Day weekend – the date most Americans view as the official start of summer.

This year, the EWG said that only 25% of the 1,400 sunscreens, lotions, lip products, and makeups that claim sun protection properties met its standards.

Courtesy of the U.S. Food and Drug Administration

"The vast majority of sunscreens available to the consumer aren’t as good as most people think they are, but there are a handful of products that rise above the rest," Sonya Lunder, senior research analyst at EWG and lead author of the report, said in a statement. "The best advice for concerned consumers is to use sun-protective clothing, stay in the shade to reduce intense sun exposure, and schedule regular skin examinations by a doctor," she said.

The EWG’s pronouncements are not without controversy. The group claimed in its press release that part of the reason that melanoma has been on the rise may be caused by "the decades of deceptive marketing claims by sunscreen manufacturers."

But your patients need not panic if their favorite sunscreen didn’t make the EWG list, according to the American Academy of Dermatology. The AAD’s position on sunscreens is practical: "The best type of sunscreen is the one you will use again and again," said Dr. Henry W. Lim, chairman of the dermatology department at Henry Ford Hospital in Detroit, in a general AAD statement on sunscreen issued on May 20.

"Just be sure to choose one that offers broad-spectrum protection, has an SPF of 30 or greater, and is water resistant," said Dr. Lim.

However, the AAD emphasized in the statement that seeking shade and wearing protective clothing are also important actions to avoid excessive sun exposure and reduce the risk of skin cancer.

The Food and Drug Administration does regulate sunscreens, having issued a final rule governing much about the products in June 2011. Most of the regulations went into effect in June 2012, but products did not start appearing with the new labels until January.

Manufacturers cannot claim that their products are waterproof or sweatproof. Products can be labeled broad spectrum if they prove to the agency that they protect against both ultraviolet B radiation (UVB) and ultraviolet A radiation (UVA) and have a sun protection factor of 15 or higher.

The EWG also says that the FDA should stop manufacturers from selling products with an SPF of 50 or higher, saying they lead consumers to spend more time in the sun than is advisable. This year, the agency will examine whether those products provide any better protection than an SPF 50 sunscreen. The agency proposed in June 2011 that sunscreens with an SPF greater than 50 be labeled "SPF 50–plus," but nothing further has been issued.

According to the EWG, its analysis of 750 beach and sport sunscreens found that the new FDA rules have not led to sunscreens that are better than those sold in the years before the ruling. It gave only 184 of them its thumbs up. Similarly, for other products that claimed to have sun protection, the EWG only recommended 22 moisturizers, 18 lip balms, and 16 kinds of makeup.

The EWG also said that consumers should not use spray sunscreens.

The AAD agreed that sprays may not be as effective because the individual might not use enough to cover all sun-exposed areas of the body.

The EWG also said that Americans should not use products that contain retinyl palmitate or oxybenzone. The group claims that retinyl palmitate is carcinogenic, and that oxybenzone is an endocrine disrupter. About half of the beach and sport sunscreens in the EWG 2013 list contain oxybenzone, the group said.

The AAD has refuted the EWG’s claims about retinyl palmitate and oxybenzone in the past.

[email protected]

On Twitter @aliciaault

How do you advise your patients about sunscreen? Some fodder for discussion (or possibly more confusion) comes from the Environmental Working Group, which has released its annual list of which sunscreens it deems both safe and effective – according to its criteria.

The Environmental Working Group (EWG), a nonprofit environmental health research and advocacy organization based in Washington, has issued the list for the past 7 years, just before Memorial Day weekend – the date most Americans view as the official start of summer.

This year, the EWG said that only 25% of the 1,400 sunscreens, lotions, lip products, and makeups that claim sun protection properties met its standards.

Courtesy of the U.S. Food and Drug Administration

"The vast majority of sunscreens available to the consumer aren’t as good as most people think they are, but there are a handful of products that rise above the rest," Sonya Lunder, senior research analyst at EWG and lead author of the report, said in a statement. "The best advice for concerned consumers is to use sun-protective clothing, stay in the shade to reduce intense sun exposure, and schedule regular skin examinations by a doctor," she said.

The EWG’s pronouncements are not without controversy. The group claimed in its press release that part of the reason that melanoma has been on the rise may be caused by "the decades of deceptive marketing claims by sunscreen manufacturers."

But your patients need not panic if their favorite sunscreen didn’t make the EWG list, according to the American Academy of Dermatology. The AAD’s position on sunscreens is practical: "The best type of sunscreen is the one you will use again and again," said Dr. Henry W. Lim, chairman of the dermatology department at Henry Ford Hospital in Detroit, in a general AAD statement on sunscreen issued on May 20.

"Just be sure to choose one that offers broad-spectrum protection, has an SPF of 30 or greater, and is water resistant," said Dr. Lim.

However, the AAD emphasized in the statement that seeking shade and wearing protective clothing are also important actions to avoid excessive sun exposure and reduce the risk of skin cancer.

The Food and Drug Administration does regulate sunscreens, having issued a final rule governing much about the products in June 2011. Most of the regulations went into effect in June 2012, but products did not start appearing with the new labels until January.

Manufacturers cannot claim that their products are waterproof or sweatproof. Products can be labeled broad spectrum if they prove to the agency that they protect against both ultraviolet B radiation (UVB) and ultraviolet A radiation (UVA) and have a sun protection factor of 15 or higher.

The EWG also says that the FDA should stop manufacturers from selling products with an SPF of 50 or higher, saying they lead consumers to spend more time in the sun than is advisable. This year, the agency will examine whether those products provide any better protection than an SPF 50 sunscreen. The agency proposed in June 2011 that sunscreens with an SPF greater than 50 be labeled "SPF 50–plus," but nothing further has been issued.

According to the EWG, its analysis of 750 beach and sport sunscreens found that the new FDA rules have not led to sunscreens that are better than those sold in the years before the ruling. It gave only 184 of them its thumbs up. Similarly, for other products that claimed to have sun protection, the EWG only recommended 22 moisturizers, 18 lip balms, and 16 kinds of makeup.

The EWG also said that consumers should not use spray sunscreens.

The AAD agreed that sprays may not be as effective because the individual might not use enough to cover all sun-exposed areas of the body.

The EWG also said that Americans should not use products that contain retinyl palmitate or oxybenzone. The group claims that retinyl palmitate is carcinogenic, and that oxybenzone is an endocrine disrupter. About half of the beach and sport sunscreens in the EWG 2013 list contain oxybenzone, the group said.

The AAD has refuted the EWG’s claims about retinyl palmitate and oxybenzone in the past.

[email protected]

On Twitter @aliciaault

How do you advise your patients about sunscreen? Some fodder for discussion (or possibly more confusion) comes from the Environmental Working Group, which has released its annual list of which sunscreens it deems both safe and effective – according to its criteria.

The Environmental Working Group (EWG), a nonprofit environmental health research and advocacy organization based in Washington, has issued the list for the past 7 years, just before Memorial Day weekend – the date most Americans view as the official start of summer.

This year, the EWG said that only 25% of the 1,400 sunscreens, lotions, lip products, and makeups that claim sun protection properties met its standards.

Courtesy of the U.S. Food and Drug Administration

"The vast majority of sunscreens available to the consumer aren’t as good as most people think they are, but there are a handful of products that rise above the rest," Sonya Lunder, senior research analyst at EWG and lead author of the report, said in a statement. "The best advice for concerned consumers is to use sun-protective clothing, stay in the shade to reduce intense sun exposure, and schedule regular skin examinations by a doctor," she said.

The EWG’s pronouncements are not without controversy. The group claimed in its press release that part of the reason that melanoma has been on the rise may be caused by "the decades of deceptive marketing claims by sunscreen manufacturers."

But your patients need not panic if their favorite sunscreen didn’t make the EWG list, according to the American Academy of Dermatology. The AAD’s position on sunscreens is practical: "The best type of sunscreen is the one you will use again and again," said Dr. Henry W. Lim, chairman of the dermatology department at Henry Ford Hospital in Detroit, in a general AAD statement on sunscreen issued on May 20.

"Just be sure to choose one that offers broad-spectrum protection, has an SPF of 30 or greater, and is water resistant," said Dr. Lim.

However, the AAD emphasized in the statement that seeking shade and wearing protective clothing are also important actions to avoid excessive sun exposure and reduce the risk of skin cancer.

The Food and Drug Administration does regulate sunscreens, having issued a final rule governing much about the products in June 2011. Most of the regulations went into effect in June 2012, but products did not start appearing with the new labels until January.

Manufacturers cannot claim that their products are waterproof or sweatproof. Products can be labeled broad spectrum if they prove to the agency that they protect against both ultraviolet B radiation (UVB) and ultraviolet A radiation (UVA) and have a sun protection factor of 15 or higher.

The EWG also says that the FDA should stop manufacturers from selling products with an SPF of 50 or higher, saying they lead consumers to spend more time in the sun than is advisable. This year, the agency will examine whether those products provide any better protection than an SPF 50 sunscreen. The agency proposed in June 2011 that sunscreens with an SPF greater than 50 be labeled "SPF 50–plus," but nothing further has been issued.

According to the EWG, its analysis of 750 beach and sport sunscreens found that the new FDA rules have not led to sunscreens that are better than those sold in the years before the ruling. It gave only 184 of them its thumbs up. Similarly, for other products that claimed to have sun protection, the EWG only recommended 22 moisturizers, 18 lip balms, and 16 kinds of makeup.

The EWG also said that consumers should not use spray sunscreens.

The AAD agreed that sprays may not be as effective because the individual might not use enough to cover all sun-exposed areas of the body.

The EWG also said that Americans should not use products that contain retinyl palmitate or oxybenzone. The group claims that retinyl palmitate is carcinogenic, and that oxybenzone is an endocrine disrupter. About half of the beach and sport sunscreens in the EWG 2013 list contain oxybenzone, the group said.

The AAD has refuted the EWG’s claims about retinyl palmitate and oxybenzone in the past.

[email protected]

On Twitter @aliciaault

Hitting metastatic melanoma with two immunotherapies, each targeted to a different metabolic pathway, has shown some preliminary success in an early study.

Ipilimumab (Yervoy) used in combination with the investigational drug nivolumab shrank stage-III and -IV melanomas in approximately half of 37 evaluable patients in a phase-I study. Tumor reductions of at least 80% were seen at 12 weeks in 11 of 37 (30%) of patients and 90% of all patients who have responded continue to respond to therapy, Dr. Jedd D. Wolchok said at a press briefing sponsored by the American Society of Clinical Oncology highlighting research to be presented at its annual meeting.

Phase-I trials are conducted to examine drug safety and give indications of dose ranges; they do not allow conclusions about efficacy. A randomized phase-III trial of the nivolumab/ipilimumab combination as first-line therapy for patients with advanced melanoma is scheduled to begin in June.

Ipilimumab is a CTLA-4 inhibitor approved for the treatment of metastatic melanoma. Nivolumab is an investigational PD-1 inhibitor that has shown activity when used alone against melanoma and other cancers.

"The rapidity and magnitude of the responses are what’s so striking," Dr. Wolchok said. "We were particularly impressed that the drugs work together so well" and show that two immunotherapies offer a promising strategy for advanced melanoma.

For the trial, patients who had inoperable stage-III and stage-IV melanoma and had undergone up to three prior therapies were assigned to one of six treatment arms. Dr. Wolchok of Memorial Sloan-Kettering Cancer Center, New York, presented results on 37 evaluable patients in three completed treatment arms, in which patients received concurrent treatment with the two drugs.

In the phase-I study, nivolumab and ipilimumab were given every 3 weeks for four doses, followed by nivolumab alone every 3 weeks for four doses. At week 24, patients began to receive one concurrent combination treatment every 3 months.

The first arm of 14 patients received 3 mg/kg of ipilimumab plus 0.3 mg/kg of nivolumab, the second arm of 17 patients received 3 mg/kg of ipilimumab plus 1 mg/kg of nivolumab, and the third arm of 6 patients received 3 mg/kg of ipilimumab plus 3 mg/kg of nivolumab. In those three arms, tumor shrinkage rates were 21%, 47%, and 50%, respectively. Tumor reductions of at least 80% were seen in 29%, 41%, and 0%, respectively.

The responses to therapy were rapid for an immunotherapy – three out of four patients who responded to the concurrent treatment experienced tumor reduction within the first 3 months, which is faster than with single-agent ipilimumab, according to Dr. Wolchok.

Two of the remaining three arms of the study enrolled patients who had undergone prior ipilimumab treatment. Those patients received only nivolumab every 2 weeks for up to 48 treatments. Although the data are still preliminary, 4 of 16 evaluable patients in the study arm given nivolumab at 1 mg/kg had at least 80% tumor shrinkage after 8 weeks, even though they initially had little benefit from ipilimumab.

In the concurrently treated patients, grade 3-4 side effects – primarily due to asymptomatic lipase, AST, and ALT abnormalities – occurred in 28 of 53 patients (53%).

With sequenced treatment, grade 3-4 side effects occurred in 6 of 33 patients (18%).

Side effects were managed using standard protocols and no treatment-related deaths were reported.

The nivolumab/ipilimumab combination also is being investigated in non–small cell lung cancer and renal cell carcinoma.

The research was supported by Bristol-Myers Squibb. Dr. Wolchok serves in consultant or advisory roles with, and receives research funding from, Bristol-Meyers Squibb.

[email protected]

Hitting metastatic melanoma with two immunotherapies, each targeted to a different metabolic pathway, has shown some preliminary success in an early study.

Ipilimumab (Yervoy) used in combination with the investigational drug nivolumab shrank stage-III and -IV melanomas in approximately half of 37 evaluable patients in a phase-I study. Tumor reductions of at least 80% were seen at 12 weeks in 11 of 37 (30%) of patients and 90% of all patients who have responded continue to respond to therapy, Dr. Jedd D. Wolchok said at a press briefing sponsored by the American Society of Clinical Oncology highlighting research to be presented at its annual meeting.

Phase-I trials are conducted to examine drug safety and give indications of dose ranges; they do not allow conclusions about efficacy. A randomized phase-III trial of the nivolumab/ipilimumab combination as first-line therapy for patients with advanced melanoma is scheduled to begin in June.

Ipilimumab is a CTLA-4 inhibitor approved for the treatment of metastatic melanoma. Nivolumab is an investigational PD-1 inhibitor that has shown activity when used alone against melanoma and other cancers.

"The rapidity and magnitude of the responses are what’s so striking," Dr. Wolchok said. "We were particularly impressed that the drugs work together so well" and show that two immunotherapies offer a promising strategy for advanced melanoma.

For the trial, patients who had inoperable stage-III and stage-IV melanoma and had undergone up to three prior therapies were assigned to one of six treatment arms. Dr. Wolchok of Memorial Sloan-Kettering Cancer Center, New York, presented results on 37 evaluable patients in three completed treatment arms, in which patients received concurrent treatment with the two drugs.

In the phase-I study, nivolumab and ipilimumab were given every 3 weeks for four doses, followed by nivolumab alone every 3 weeks for four doses. At week 24, patients began to receive one concurrent combination treatment every 3 months.

The first arm of 14 patients received 3 mg/kg of ipilimumab plus 0.3 mg/kg of nivolumab, the second arm of 17 patients received 3 mg/kg of ipilimumab plus 1 mg/kg of nivolumab, and the third arm of 6 patients received 3 mg/kg of ipilimumab plus 3 mg/kg of nivolumab. In those three arms, tumor shrinkage rates were 21%, 47%, and 50%, respectively. Tumor reductions of at least 80% were seen in 29%, 41%, and 0%, respectively.

The responses to therapy were rapid for an immunotherapy – three out of four patients who responded to the concurrent treatment experienced tumor reduction within the first 3 months, which is faster than with single-agent ipilimumab, according to Dr. Wolchok.

Two of the remaining three arms of the study enrolled patients who had undergone prior ipilimumab treatment. Those patients received only nivolumab every 2 weeks for up to 48 treatments. Although the data are still preliminary, 4 of 16 evaluable patients in the study arm given nivolumab at 1 mg/kg had at least 80% tumor shrinkage after 8 weeks, even though they initially had little benefit from ipilimumab.

In the concurrently treated patients, grade 3-4 side effects – primarily due to asymptomatic lipase, AST, and ALT abnormalities – occurred in 28 of 53 patients (53%).

With sequenced treatment, grade 3-4 side effects occurred in 6 of 33 patients (18%).

Side effects were managed using standard protocols and no treatment-related deaths were reported.

The nivolumab/ipilimumab combination also is being investigated in non–small cell lung cancer and renal cell carcinoma.

The research was supported by Bristol-Myers Squibb. Dr. Wolchok serves in consultant or advisory roles with, and receives research funding from, Bristol-Meyers Squibb.

[email protected]

Hitting metastatic melanoma with two immunotherapies, each targeted to a different metabolic pathway, has shown some preliminary success in an early study.

Ipilimumab (Yervoy) used in combination with the investigational drug nivolumab shrank stage-III and -IV melanomas in approximately half of 37 evaluable patients in a phase-I study. Tumor reductions of at least 80% were seen at 12 weeks in 11 of 37 (30%) of patients and 90% of all patients who have responded continue to respond to therapy, Dr. Jedd D. Wolchok said at a press briefing sponsored by the American Society of Clinical Oncology highlighting research to be presented at its annual meeting.

Phase-I trials are conducted to examine drug safety and give indications of dose ranges; they do not allow conclusions about efficacy. A randomized phase-III trial of the nivolumab/ipilimumab combination as first-line therapy for patients with advanced melanoma is scheduled to begin in June.

Ipilimumab is a CTLA-4 inhibitor approved for the treatment of metastatic melanoma. Nivolumab is an investigational PD-1 inhibitor that has shown activity when used alone against melanoma and other cancers.

"The rapidity and magnitude of the responses are what’s so striking," Dr. Wolchok said. "We were particularly impressed that the drugs work together so well" and show that two immunotherapies offer a promising strategy for advanced melanoma.

For the trial, patients who had inoperable stage-III and stage-IV melanoma and had undergone up to three prior therapies were assigned to one of six treatment arms. Dr. Wolchok of Memorial Sloan-Kettering Cancer Center, New York, presented results on 37 evaluable patients in three completed treatment arms, in which patients received concurrent treatment with the two drugs.

In the phase-I study, nivolumab and ipilimumab were given every 3 weeks for four doses, followed by nivolumab alone every 3 weeks for four doses. At week 24, patients began to receive one concurrent combination treatment every 3 months.

The first arm of 14 patients received 3 mg/kg of ipilimumab plus 0.3 mg/kg of nivolumab, the second arm of 17 patients received 3 mg/kg of ipilimumab plus 1 mg/kg of nivolumab, and the third arm of 6 patients received 3 mg/kg of ipilimumab plus 3 mg/kg of nivolumab. In those three arms, tumor shrinkage rates were 21%, 47%, and 50%, respectively. Tumor reductions of at least 80% were seen in 29%, 41%, and 0%, respectively.

The responses to therapy were rapid for an immunotherapy – three out of four patients who responded to the concurrent treatment experienced tumor reduction within the first 3 months, which is faster than with single-agent ipilimumab, according to Dr. Wolchok.

Two of the remaining three arms of the study enrolled patients who had undergone prior ipilimumab treatment. Those patients received only nivolumab every 2 weeks for up to 48 treatments. Although the data are still preliminary, 4 of 16 evaluable patients in the study arm given nivolumab at 1 mg/kg had at least 80% tumor shrinkage after 8 weeks, even though they initially had little benefit from ipilimumab.

In the concurrently treated patients, grade 3-4 side effects – primarily due to asymptomatic lipase, AST, and ALT abnormalities – occurred in 28 of 53 patients (53%).

With sequenced treatment, grade 3-4 side effects occurred in 6 of 33 patients (18%).

Side effects were managed using standard protocols and no treatment-related deaths were reported.

The nivolumab/ipilimumab combination also is being investigated in non–small cell lung cancer and renal cell carcinoma.

The research was supported by Bristol-Myers Squibb. Dr. Wolchok serves in consultant or advisory roles with, and receives research funding from, Bristol-Meyers Squibb.

[email protected]

BOSTON – Sequential application of pulsed dye and Nd:YAG lasers is safe and effective for treating small basal cell carcinomas, based on data from a prospective study of patients with nodular and superficial BCC subtypes on the trunk and extremities.

The findings were presented at the annual meeting of the American Society for Laser Medicine and Surgery.

In a study of 10 patients with BCC, 7 of the 12 lesions treated with pulsed dye laser followed by Nd:YAG laser showed completed clinical and histologic clearance, said Dr. H. Ray Jalian of Massachusetts General Hospital in Boston.

"Targeting the microvasculature of BCC offers a promising new treatment approach. These tumors have large caliber feeding vessels; oftentimes these vessels are larger than the surrounding stroma," he said.

Data from a previous study (Lasers Surg. Med. 2009;41:417-42) showed a 92% regression rate of BCC lesions smaller than 1.5 cm treated with a 595 nm pulsed dye laser, Dr. Jalian noted.

The rationale for the sequential laser therapy is that pulsed dye laser energy is well absorbed by hemoglobin, which generates methemoglobin that in turn absorbs 1064 nm Nd:YAG energy, allowing the energy to penetrate to deep vessels.

"We hypothesized that targeting the vasculature of basal cells at two levels may be able to selectively destroy deeper vessels and perhaps achieve a higher cure rate," he said.

The investigators conducted a prospective study with 10 patients who had a total of 13 BCC of nodular and superficial subtypes on the trunk and extremities (1 patient with a single lesion was not available for follow-up).

The treated lesions were less than 2 cm with clearly visible margins that would be suitable for treatment with standard surgical excision. Patients with scars or infections in the area to be treated were excluded, as were those who were immunocompromised or pregnant.

The participants underwent four laser treatments 2-4 weeks apart with a 585-nm PDL set for a 7-mm spot size, 8-J/cm², 2-ms pulse duration, followed by a 1064-nm Nd:YAG laser set with a 7-mm spot, 40-J/cm², 15-ms pulse duration.

A total of 7 of the 12 lesions available for follow-up were completely cleared on both clinical and histologic evaluation. Of the eight tumors under 1 cm in size, six were completely cleared by sequential laser therapy,

Of the four patients with 5 lesions with residual disease after four laser sessions, three were on anticoagulation therapy with aspirin, and one with warfarin.

"We did see a clearance of the nodular component in most cases, but there was persistent residual superficial BCC in these patients," Dr. Jalian said.

Anticoagulation may hamper the laser effect by reducing laser-induced vascular injury, he noted.

Treatment-related side effects included erythema, scarring, and hyperpigmentation. Erythema and scarring decreased from the first treatment to the last follow-up visit, while hyperpigmentation increased slightly from the first to the third treatment, and then plateaued.

Biopsy scars improved with sequential treatments, Dr. Jalian noted.

Possible explanations for the lower success rate treating BCC compared to previous studies include the use of a slightly lower wavelength laser (585 vs. 595), and lower energy settings (8 J/cm² for 2 ms, vs. 15 J/cm² for 3 ms), and by mix of histologic subtypes, said Dr. Jalian.

"Superficial subtypes present in residual lesions suggest there may be a different vascular pattern in these lesions."

The findings also suggest that anticoagulation therapy may need to be suspended before treatment with pulsed dye, Nd:YAG, and other vascular-specific lasers, he added.

The study was internally supported. Dr. Jalian reported having no financial disclosures.

[email protected]

BOSTON – Sequential application of pulsed dye and Nd:YAG lasers is safe and effective for treating small basal cell carcinomas, based on data from a prospective study of patients with nodular and superficial BCC subtypes on the trunk and extremities.

The findings were presented at the annual meeting of the American Society for Laser Medicine and Surgery.

In a study of 10 patients with BCC, 7 of the 12 lesions treated with pulsed dye laser followed by Nd:YAG laser showed completed clinical and histologic clearance, said Dr. H. Ray Jalian of Massachusetts General Hospital in Boston.

"Targeting the microvasculature of BCC offers a promising new treatment approach. These tumors have large caliber feeding vessels; oftentimes these vessels are larger than the surrounding stroma," he said.

Data from a previous study (Lasers Surg. Med. 2009;41:417-42) showed a 92% regression rate of BCC lesions smaller than 1.5 cm treated with a 595 nm pulsed dye laser, Dr. Jalian noted.

The rationale for the sequential laser therapy is that pulsed dye laser energy is well absorbed by hemoglobin, which generates methemoglobin that in turn absorbs 1064 nm Nd:YAG energy, allowing the energy to penetrate to deep vessels.

"We hypothesized that targeting the vasculature of basal cells at two levels may be able to selectively destroy deeper vessels and perhaps achieve a higher cure rate," he said.

The investigators conducted a prospective study with 10 patients who had a total of 13 BCC of nodular and superficial subtypes on the trunk and extremities (1 patient with a single lesion was not available for follow-up).

The treated lesions were less than 2 cm with clearly visible margins that would be suitable for treatment with standard surgical excision. Patients with scars or infections in the area to be treated were excluded, as were those who were immunocompromised or pregnant.

The participants underwent four laser treatments 2-4 weeks apart with a 585-nm PDL set for a 7-mm spot size, 8-J/cm², 2-ms pulse duration, followed by a 1064-nm Nd:YAG laser set with a 7-mm spot, 40-J/cm², 15-ms pulse duration.

A total of 7 of the 12 lesions available for follow-up were completely cleared on both clinical and histologic evaluation. Of the eight tumors under 1 cm in size, six were completely cleared by sequential laser therapy,

Of the four patients with 5 lesions with residual disease after four laser sessions, three were on anticoagulation therapy with aspirin, and one with warfarin.

"We did see a clearance of the nodular component in most cases, but there was persistent residual superficial BCC in these patients," Dr. Jalian said.

Anticoagulation may hamper the laser effect by reducing laser-induced vascular injury, he noted.

Treatment-related side effects included erythema, scarring, and hyperpigmentation. Erythema and scarring decreased from the first treatment to the last follow-up visit, while hyperpigmentation increased slightly from the first to the third treatment, and then plateaued.

Biopsy scars improved with sequential treatments, Dr. Jalian noted.

Possible explanations for the lower success rate treating BCC compared to previous studies include the use of a slightly lower wavelength laser (585 vs. 595), and lower energy settings (8 J/cm² for 2 ms, vs. 15 J/cm² for 3 ms), and by mix of histologic subtypes, said Dr. Jalian.

"Superficial subtypes present in residual lesions suggest there may be a different vascular pattern in these lesions."

The findings also suggest that anticoagulation therapy may need to be suspended before treatment with pulsed dye, Nd:YAG, and other vascular-specific lasers, he added.

The study was internally supported. Dr. Jalian reported having no financial disclosures.

[email protected]

BOSTON – Sequential application of pulsed dye and Nd:YAG lasers is safe and effective for treating small basal cell carcinomas, based on data from a prospective study of patients with nodular and superficial BCC subtypes on the trunk and extremities.

The findings were presented at the annual meeting of the American Society for Laser Medicine and Surgery.

In a study of 10 patients with BCC, 7 of the 12 lesions treated with pulsed dye laser followed by Nd:YAG laser showed completed clinical and histologic clearance, said Dr. H. Ray Jalian of Massachusetts General Hospital in Boston.

"Targeting the microvasculature of BCC offers a promising new treatment approach. These tumors have large caliber feeding vessels; oftentimes these vessels are larger than the surrounding stroma," he said.

Data from a previous study (Lasers Surg. Med. 2009;41:417-42) showed a 92% regression rate of BCC lesions smaller than 1.5 cm treated with a 595 nm pulsed dye laser, Dr. Jalian noted.

The rationale for the sequential laser therapy is that pulsed dye laser energy is well absorbed by hemoglobin, which generates methemoglobin that in turn absorbs 1064 nm Nd:YAG energy, allowing the energy to penetrate to deep vessels.

"We hypothesized that targeting the vasculature of basal cells at two levels may be able to selectively destroy deeper vessels and perhaps achieve a higher cure rate," he said.

The investigators conducted a prospective study with 10 patients who had a total of 13 BCC of nodular and superficial subtypes on the trunk and extremities (1 patient with a single lesion was not available for follow-up).

The treated lesions were less than 2 cm with clearly visible margins that would be suitable for treatment with standard surgical excision. Patients with scars or infections in the area to be treated were excluded, as were those who were immunocompromised or pregnant.

The participants underwent four laser treatments 2-4 weeks apart with a 585-nm PDL set for a 7-mm spot size, 8-J/cm², 2-ms pulse duration, followed by a 1064-nm Nd:YAG laser set with a 7-mm spot, 40-J/cm², 15-ms pulse duration.

A total of 7 of the 12 lesions available for follow-up were completely cleared on both clinical and histologic evaluation. Of the eight tumors under 1 cm in size, six were completely cleared by sequential laser therapy,

Of the four patients with 5 lesions with residual disease after four laser sessions, three were on anticoagulation therapy with aspirin, and one with warfarin.

"We did see a clearance of the nodular component in most cases, but there was persistent residual superficial BCC in these patients," Dr. Jalian said.

Anticoagulation may hamper the laser effect by reducing laser-induced vascular injury, he noted.

Treatment-related side effects included erythema, scarring, and hyperpigmentation. Erythema and scarring decreased from the first treatment to the last follow-up visit, while hyperpigmentation increased slightly from the first to the third treatment, and then plateaued.

Biopsy scars improved with sequential treatments, Dr. Jalian noted.

Possible explanations for the lower success rate treating BCC compared to previous studies include the use of a slightly lower wavelength laser (585 vs. 595), and lower energy settings (8 J/cm² for 2 ms, vs. 15 J/cm² for 3 ms), and by mix of histologic subtypes, said Dr. Jalian.

"Superficial subtypes present in residual lesions suggest there may be a different vascular pattern in these lesions."

The findings also suggest that anticoagulation therapy may need to be suspended before treatment with pulsed dye, Nd:YAG, and other vascular-specific lasers, he added.

The study was internally supported. Dr. Jalian reported having no financial disclosures.

[email protected]