Melanoma

CHICAGO – The case against performing a complete lymph node dissection in patients with melanoma who have micrometastases in their sentinel lymph node just got stronger in light of findings from a randomized, phase III clinical trial conducted by the German Dermatologic Cooperative Oncology Group (DeCOG).

With 483 patients studied and a median follow-up approaching 3 years, the rate of distant metastasis–free survival did not differ significantly between those who had a complete lymph node dissection and those who had simple watchful waiting, with just 0.3% separating the groups, the investigators reported at the annual meeting of the American Society of Clinical Oncology. Most other key outcomes were likewise statistically indistinguishable between groups.

“This is the first study which tested the general recommendation of complete lymphadenectomy in patients with positive nodes,” senior investigator Dr. Claus Garbe, a professor of dermatology at the University of Tübingen (Germany), said in a press briefing. “We cannot confirm this recommendation, and we expect that the surgical [practice] will change.”

However, Dr. Lynn Schuchter, an ASCO expert, as well as chief of hematology oncology and the C. Willard Robinson Professor of Hematology-Oncology at Penn Medicine in Philadelphia, took a more cautious view, saying that the findings require confirmation before being widely adopted into clinical practice.

“I would say this is a really important study. However, it’s a relatively small study, and I don’t think we would make a complete change in our recommendations yet based upon this study,” she commented.

The ongoing international Multicenter Selective Lymphadenectomy Trial II (MSLT-II), which has a target enrollment of about 1,900 patients and is designed to detect a smaller difference between groups, will provide further information on this issue, according to Dr. Schuchter. “So I think we’ll wait in terms of making definitive changes in our management, for the results of another, larger study with longer follow-up,” she said. “But [the German study] gives us, in that patient who is very concerned about lymphedema ... pertinent information to feel comfortable considering more of a watch-and-wait approach, in terms of monitoring somebody and not doing that surgery.”

Dr. Garbe and colleagues enrolled in their trial patients who underwent resection of a primary cutaneous melanoma of the trunk or extremities at least 1.00 mm in thickness and were determined to have stage III disease with a positive sentinel node containing individual tumor cells or micrometastases. They were randomly assigned to observation only or complete lymph node dissection. Both groups had a lymph node ultrasound exam every 3 months and CT/MRI or PET scans every 6 months.

With a median follow-up of 35 months, patients who had the complete lymph node dissection were about half as likely to develop regional metastases as peers who had watchful waiting (8.3% vs. 14.6%). But the groups did not differ significantly with respect to 3- and 5-year rates of recurrence-free survival, distant metastasis–free survival (the trial’s primary endpoint), and melanoma-specific survival.

The investigators plan to repeat their analysis in 3 years but do not expect the findings will change, according to Dr. Garbe, as the large majority of melanoma recurrences happen in the first 3 years after initial diagnosis.

Dr. Garbe disclosed ties to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Roche Pharma AG. The trial was funded by German Cancer Aid.

CHICAGO – The case against performing a complete lymph node dissection in patients with melanoma who have micrometastases in their sentinel lymph node just got stronger in light of findings from a randomized, phase III clinical trial conducted by the German Dermatologic Cooperative Oncology Group (DeCOG).

With 483 patients studied and a median follow-up approaching 3 years, the rate of distant metastasis–free survival did not differ significantly between those who had a complete lymph node dissection and those who had simple watchful waiting, with just 0.3% separating the groups, the investigators reported at the annual meeting of the American Society of Clinical Oncology. Most other key outcomes were likewise statistically indistinguishable between groups.

“This is the first study which tested the general recommendation of complete lymphadenectomy in patients with positive nodes,” senior investigator Dr. Claus Garbe, a professor of dermatology at the University of Tübingen (Germany), said in a press briefing. “We cannot confirm this recommendation, and we expect that the surgical [practice] will change.”

However, Dr. Lynn Schuchter, an ASCO expert, as well as chief of hematology oncology and the C. Willard Robinson Professor of Hematology-Oncology at Penn Medicine in Philadelphia, took a more cautious view, saying that the findings require confirmation before being widely adopted into clinical practice.

“I would say this is a really important study. However, it’s a relatively small study, and I don’t think we would make a complete change in our recommendations yet based upon this study,” she commented.

The ongoing international Multicenter Selective Lymphadenectomy Trial II (MSLT-II), which has a target enrollment of about 1,900 patients and is designed to detect a smaller difference between groups, will provide further information on this issue, according to Dr. Schuchter. “So I think we’ll wait in terms of making definitive changes in our management, for the results of another, larger study with longer follow-up,” she said. “But [the German study] gives us, in that patient who is very concerned about lymphedema ... pertinent information to feel comfortable considering more of a watch-and-wait approach, in terms of monitoring somebody and not doing that surgery.”

Dr. Garbe and colleagues enrolled in their trial patients who underwent resection of a primary cutaneous melanoma of the trunk or extremities at least 1.00 mm in thickness and were determined to have stage III disease with a positive sentinel node containing individual tumor cells or micrometastases. They were randomly assigned to observation only or complete lymph node dissection. Both groups had a lymph node ultrasound exam every 3 months and CT/MRI or PET scans every 6 months.

With a median follow-up of 35 months, patients who had the complete lymph node dissection were about half as likely to develop regional metastases as peers who had watchful waiting (8.3% vs. 14.6%). But the groups did not differ significantly with respect to 3- and 5-year rates of recurrence-free survival, distant metastasis–free survival (the trial’s primary endpoint), and melanoma-specific survival.

The investigators plan to repeat their analysis in 3 years but do not expect the findings will change, according to Dr. Garbe, as the large majority of melanoma recurrences happen in the first 3 years after initial diagnosis.

Dr. Garbe disclosed ties to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Roche Pharma AG. The trial was funded by German Cancer Aid.

CHICAGO – The case against performing a complete lymph node dissection in patients with melanoma who have micrometastases in their sentinel lymph node just got stronger in light of findings from a randomized, phase III clinical trial conducted by the German Dermatologic Cooperative Oncology Group (DeCOG).

With 483 patients studied and a median follow-up approaching 3 years, the rate of distant metastasis–free survival did not differ significantly between those who had a complete lymph node dissection and those who had simple watchful waiting, with just 0.3% separating the groups, the investigators reported at the annual meeting of the American Society of Clinical Oncology. Most other key outcomes were likewise statistically indistinguishable between groups.

“This is the first study which tested the general recommendation of complete lymphadenectomy in patients with positive nodes,” senior investigator Dr. Claus Garbe, a professor of dermatology at the University of Tübingen (Germany), said in a press briefing. “We cannot confirm this recommendation, and we expect that the surgical [practice] will change.”

However, Dr. Lynn Schuchter, an ASCO expert, as well as chief of hematology oncology and the C. Willard Robinson Professor of Hematology-Oncology at Penn Medicine in Philadelphia, took a more cautious view, saying that the findings require confirmation before being widely adopted into clinical practice.

“I would say this is a really important study. However, it’s a relatively small study, and I don’t think we would make a complete change in our recommendations yet based upon this study,” she commented.

The ongoing international Multicenter Selective Lymphadenectomy Trial II (MSLT-II), which has a target enrollment of about 1,900 patients and is designed to detect a smaller difference between groups, will provide further information on this issue, according to Dr. Schuchter. “So I think we’ll wait in terms of making definitive changes in our management, for the results of another, larger study with longer follow-up,” she said. “But [the German study] gives us, in that patient who is very concerned about lymphedema ... pertinent information to feel comfortable considering more of a watch-and-wait approach, in terms of monitoring somebody and not doing that surgery.”

Dr. Garbe and colleagues enrolled in their trial patients who underwent resection of a primary cutaneous melanoma of the trunk or extremities at least 1.00 mm in thickness and were determined to have stage III disease with a positive sentinel node containing individual tumor cells or micrometastases. They were randomly assigned to observation only or complete lymph node dissection. Both groups had a lymph node ultrasound exam every 3 months and CT/MRI or PET scans every 6 months.

With a median follow-up of 35 months, patients who had the complete lymph node dissection were about half as likely to develop regional metastases as peers who had watchful waiting (8.3% vs. 14.6%). But the groups did not differ significantly with respect to 3- and 5-year rates of recurrence-free survival, distant metastasis–free survival (the trial’s primary endpoint), and melanoma-specific survival.

The investigators plan to repeat their analysis in 3 years but do not expect the findings will change, according to Dr. Garbe, as the large majority of melanoma recurrences happen in the first 3 years after initial diagnosis.

Dr. Garbe disclosed ties to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Roche Pharma AG. The trial was funded by German Cancer Aid.

CHICAGO – Complete lymph node dissection did not improve survival in a prospective, randomized trial of 483 patients with stage III melanoma and micrometastases in their sentinel lymph node biopsies.

After nearly 3 years of follow-up, the point at which 80% of melanoma recurrences take place, patients in an observation group had outcomes similar to those of patients who underwent complete lymph node dissection.

The findings mark “the beginning of the end” for complete lymph node dissection in melanoma patients with micrometastases in sentinal lymph nodes, Dr. Claus Garbe said at the annual meeting of the American Society for Clinical Oncology.

Watch our video interview to learn more about the study and its likely impact on clinical guidelines for patients with melanoma and micrometastases.

CHICAGO – Complete lymph node dissection did not improve survival in a prospective, randomized trial of 483 patients with stage III melanoma and micrometastases in their sentinel lymph node biopsies.

After nearly 3 years of follow-up, the point at which 80% of melanoma recurrences take place, patients in an observation group had outcomes similar to those of patients who underwent complete lymph node dissection.

The findings mark “the beginning of the end” for complete lymph node dissection in melanoma patients with micrometastases in sentinal lymph nodes, Dr. Claus Garbe said at the annual meeting of the American Society for Clinical Oncology.

Watch our video interview to learn more about the study and its likely impact on clinical guidelines for patients with melanoma and micrometastases.

CHICAGO – Complete lymph node dissection did not improve survival in a prospective, randomized trial of 483 patients with stage III melanoma and micrometastases in their sentinel lymph node biopsies.

After nearly 3 years of follow-up, the point at which 80% of melanoma recurrences take place, patients in an observation group had outcomes similar to those of patients who underwent complete lymph node dissection.

The findings mark “the beginning of the end” for complete lymph node dissection in melanoma patients with micrometastases in sentinal lymph nodes, Dr. Claus Garbe said at the annual meeting of the American Society for Clinical Oncology.

Watch our video interview to learn more about the study and its likely impact on clinical guidelines for patients with melanoma and micrometastases.

Treatment with the oncolytic immunotherapy talimogene laherparepvec (T-VEC) resulted in significantly longer rates of durable response and overall response, compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF), according to results from the phase III OPTiM trial reported in the Journal of Clinical Oncology.

“To our knowledge, OPTiM is the first randomized, controlled, phase III study evaluating an oncolytic immunotherapy to demonstrate a therapeutic benefit in melanoma,” wrote Dr. Robert Andtbacka, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, and colleagues (J. Clin. Onc. 2015 May 26 [doi:10.1200/JCO.2014.58.3377]).

Patients who received T-VEC vs. subcutaneous GM-CSF had significantly improved rates of durable response, defined as responses lasting 6 months or more, (16.3% vs. 2.1%; P < .001), as well as improved overall response rates (26.4% vs. 5.7% ; P < .001). Complete responses were achieved in 10.8% of the T-VEC arm (32 patients) and < 1% (1 patient) in the GM-CSF arm. Median overall survival was 23.3 months for T-VEC and 18.9 months for GM-CSF (P = .051).

Differences in durable response rates and overall response rates between the T-VEC and GM-CSF arms were greater among patients with stage IIIb or IIIC (33% vs. 0%) and IVM1a disease (16% vs. 2%) than in patients with stage IVM1b (3% vs. 4%) or IVM1c disease (7% vs. 3%). This may be because of insufficient time for the immunotherapy to benefit patients with visceral disease, or because injection of T-VEC into dermal, subcutaneous, and nodal metastases may activate an immune response that preferentially targets metastases in similar anatomic sites.

Among patients in the T-VEC arm who achieved a response, 54% had disease progression prior to response. This pseudoprogression is consistent with other immunotherapies and illustrates the importance of continuing treatment in stable patients despite increasing lesions, the investigators noted.

Based on a modified herpes simplex virus type 1, T-VEC is an oncolytic virus designed to replicate in and lyse tumor cells while promoting an antitumor immune response.

Adverse events more frequently observed in the T-VEC group were flu-like symptoms, including chills, pyrexia, nausea, and fatigue. Incidence of grade 3 or 4 adverse events was 11% for T-VEC and 5% for GM-CSF. The tolerable safety profile of T-VEC is an important factor in considering combined immunotherapy approaches, wrote Dr. Robert Andtbacka and associates.

“The evidence of local and systemic immune responses with T-VEC supports combinations with other immunotherapies as a rational approach. A phase 1b/2 study of T-VEC and ipilimumab is evaluating the safety and efficacy of this combination,” they wrote.

Treatment with the oncolytic immunotherapy talimogene laherparepvec (T-VEC) resulted in significantly longer rates of durable response and overall response, compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF), according to results from the phase III OPTiM trial reported in the Journal of Clinical Oncology.

“To our knowledge, OPTiM is the first randomized, controlled, phase III study evaluating an oncolytic immunotherapy to demonstrate a therapeutic benefit in melanoma,” wrote Dr. Robert Andtbacka, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, and colleagues (J. Clin. Onc. 2015 May 26 [doi:10.1200/JCO.2014.58.3377]).

Patients who received T-VEC vs. subcutaneous GM-CSF had significantly improved rates of durable response, defined as responses lasting 6 months or more, (16.3% vs. 2.1%; P < .001), as well as improved overall response rates (26.4% vs. 5.7% ; P < .001). Complete responses were achieved in 10.8% of the T-VEC arm (32 patients) and < 1% (1 patient) in the GM-CSF arm. Median overall survival was 23.3 months for T-VEC and 18.9 months for GM-CSF (P = .051).

Differences in durable response rates and overall response rates between the T-VEC and GM-CSF arms were greater among patients with stage IIIb or IIIC (33% vs. 0%) and IVM1a disease (16% vs. 2%) than in patients with stage IVM1b (3% vs. 4%) or IVM1c disease (7% vs. 3%). This may be because of insufficient time for the immunotherapy to benefit patients with visceral disease, or because injection of T-VEC into dermal, subcutaneous, and nodal metastases may activate an immune response that preferentially targets metastases in similar anatomic sites.

Among patients in the T-VEC arm who achieved a response, 54% had disease progression prior to response. This pseudoprogression is consistent with other immunotherapies and illustrates the importance of continuing treatment in stable patients despite increasing lesions, the investigators noted.

Based on a modified herpes simplex virus type 1, T-VEC is an oncolytic virus designed to replicate in and lyse tumor cells while promoting an antitumor immune response.

Adverse events more frequently observed in the T-VEC group were flu-like symptoms, including chills, pyrexia, nausea, and fatigue. Incidence of grade 3 or 4 adverse events was 11% for T-VEC and 5% for GM-CSF. The tolerable safety profile of T-VEC is an important factor in considering combined immunotherapy approaches, wrote Dr. Robert Andtbacka and associates.

“The evidence of local and systemic immune responses with T-VEC supports combinations with other immunotherapies as a rational approach. A phase 1b/2 study of T-VEC and ipilimumab is evaluating the safety and efficacy of this combination,” they wrote.

Treatment with the oncolytic immunotherapy talimogene laherparepvec (T-VEC) resulted in significantly longer rates of durable response and overall response, compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF), according to results from the phase III OPTiM trial reported in the Journal of Clinical Oncology.

“To our knowledge, OPTiM is the first randomized, controlled, phase III study evaluating an oncolytic immunotherapy to demonstrate a therapeutic benefit in melanoma,” wrote Dr. Robert Andtbacka, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, and colleagues (J. Clin. Onc. 2015 May 26 [doi:10.1200/JCO.2014.58.3377]).

Patients who received T-VEC vs. subcutaneous GM-CSF had significantly improved rates of durable response, defined as responses lasting 6 months or more, (16.3% vs. 2.1%; P < .001), as well as improved overall response rates (26.4% vs. 5.7% ; P < .001). Complete responses were achieved in 10.8% of the T-VEC arm (32 patients) and < 1% (1 patient) in the GM-CSF arm. Median overall survival was 23.3 months for T-VEC and 18.9 months for GM-CSF (P = .051).

Differences in durable response rates and overall response rates between the T-VEC and GM-CSF arms were greater among patients with stage IIIb or IIIC (33% vs. 0%) and IVM1a disease (16% vs. 2%) than in patients with stage IVM1b (3% vs. 4%) or IVM1c disease (7% vs. 3%). This may be because of insufficient time for the immunotherapy to benefit patients with visceral disease, or because injection of T-VEC into dermal, subcutaneous, and nodal metastases may activate an immune response that preferentially targets metastases in similar anatomic sites.

Among patients in the T-VEC arm who achieved a response, 54% had disease progression prior to response. This pseudoprogression is consistent with other immunotherapies and illustrates the importance of continuing treatment in stable patients despite increasing lesions, the investigators noted.

Based on a modified herpes simplex virus type 1, T-VEC is an oncolytic virus designed to replicate in and lyse tumor cells while promoting an antitumor immune response.

Adverse events more frequently observed in the T-VEC group were flu-like symptoms, including chills, pyrexia, nausea, and fatigue. Incidence of grade 3 or 4 adverse events was 11% for T-VEC and 5% for GM-CSF. The tolerable safety profile of T-VEC is an important factor in considering combined immunotherapy approaches, wrote Dr. Robert Andtbacka and associates.

“The evidence of local and systemic immune responses with T-VEC supports combinations with other immunotherapies as a rational approach. A phase 1b/2 study of T-VEC and ipilimumab is evaluating the safety and efficacy of this combination,” they wrote.

The back is the most common site for melanoma but is a difficult area for patients to self-inspect. In recognition of skin cancer awareness month in May, the American Academy of Dermatology (AAD) has released a new infographic emphasizing sun protection and examination of suspicious lesions on the back.

Melanoma has a high cure rate when spotted early, but research has shown that thicker melanomas, which can require more advanced treatment, are more frequently found on parts of the body that are difficult to self-inspect such as the back. Results from a 2015 survey conducted by the AAD indicated that many people do not regularly check the back for suspicious lesions. Only 36% of 1019 survey respondents said they examined the back for signs of skin cancer at least once a year, and only 35% asked someone else to help them examine hard-to-see areas of the body.

Sun protection on the back also is commonly neglected because this area can be difficult to reach, according to the AAD. Survey results indicated that 37% of respondents rarely or never applied sunscreen on the back during sun exposure, and 43% rarely or never asked someone else to help them apply sunscreen on the back. Although 1 of 3 melanomas in men is found on the back, survey results indicated that men were less likely than women to use sunscreen on the back or ask someone else to help them apply sunscreen.

In their patient education campaign “Who’s Got Your Back?” the AAD recommends checking all areas of the skin regularly and asking a family member or friend to help examine the back and other hard-to-see areas. Also, apply a broad-spectrum, water-resistant, SPF 30+ sunscreen on the back with the help of a family member or friend.

If there is no one else around to help apply sunscreen on the back, Dr. Vincent A. DeLeo, Cutis Editor-in-Chief, suggests using spray sunscreens that work when held in an upside-down position or applying sunscreen to gauze or a cloth pad that can be attached to a back scratcher or wooden spoon to act as an extension of the arm. Photoprotective clothing also is important, according to Dr. DeLeo. “It doesn’t have to be specially made clothing. Just a T-shirt with a close weave. Hold it up to the light, and if you can’t see light through it, it will probably block UV rays,” he notes.

Throughout the year, remind your patients to watch their back. Share the new AAD infographic with them, which can be obtained on the AAD Web site.

The back is the most common site for melanoma but is a difficult area for patients to self-inspect. In recognition of skin cancer awareness month in May, the American Academy of Dermatology (AAD) has released a new infographic emphasizing sun protection and examination of suspicious lesions on the back.

Melanoma has a high cure rate when spotted early, but research has shown that thicker melanomas, which can require more advanced treatment, are more frequently found on parts of the body that are difficult to self-inspect such as the back. Results from a 2015 survey conducted by the AAD indicated that many people do not regularly check the back for suspicious lesions. Only 36% of 1019 survey respondents said they examined the back for signs of skin cancer at least once a year, and only 35% asked someone else to help them examine hard-to-see areas of the body.

Sun protection on the back also is commonly neglected because this area can be difficult to reach, according to the AAD. Survey results indicated that 37% of respondents rarely or never applied sunscreen on the back during sun exposure, and 43% rarely or never asked someone else to help them apply sunscreen on the back. Although 1 of 3 melanomas in men is found on the back, survey results indicated that men were less likely than women to use sunscreen on the back or ask someone else to help them apply sunscreen.

In their patient education campaign “Who’s Got Your Back?” the AAD recommends checking all areas of the skin regularly and asking a family member or friend to help examine the back and other hard-to-see areas. Also, apply a broad-spectrum, water-resistant, SPF 30+ sunscreen on the back with the help of a family member or friend.

If there is no one else around to help apply sunscreen on the back, Dr. Vincent A. DeLeo, Cutis Editor-in-Chief, suggests using spray sunscreens that work when held in an upside-down position or applying sunscreen to gauze or a cloth pad that can be attached to a back scratcher or wooden spoon to act as an extension of the arm. Photoprotective clothing also is important, according to Dr. DeLeo. “It doesn’t have to be specially made clothing. Just a T-shirt with a close weave. Hold it up to the light, and if you can’t see light through it, it will probably block UV rays,” he notes.

Throughout the year, remind your patients to watch their back. Share the new AAD infographic with them, which can be obtained on the AAD Web site.

The back is the most common site for melanoma but is a difficult area for patients to self-inspect. In recognition of skin cancer awareness month in May, the American Academy of Dermatology (AAD) has released a new infographic emphasizing sun protection and examination of suspicious lesions on the back.

Melanoma has a high cure rate when spotted early, but research has shown that thicker melanomas, which can require more advanced treatment, are more frequently found on parts of the body that are difficult to self-inspect such as the back. Results from a 2015 survey conducted by the AAD indicated that many people do not regularly check the back for suspicious lesions. Only 36% of 1019 survey respondents said they examined the back for signs of skin cancer at least once a year, and only 35% asked someone else to help them examine hard-to-see areas of the body.

Sun protection on the back also is commonly neglected because this area can be difficult to reach, according to the AAD. Survey results indicated that 37% of respondents rarely or never applied sunscreen on the back during sun exposure, and 43% rarely or never asked someone else to help them apply sunscreen on the back. Although 1 of 3 melanomas in men is found on the back, survey results indicated that men were less likely than women to use sunscreen on the back or ask someone else to help them apply sunscreen.

In their patient education campaign “Who’s Got Your Back?” the AAD recommends checking all areas of the skin regularly and asking a family member or friend to help examine the back and other hard-to-see areas. Also, apply a broad-spectrum, water-resistant, SPF 30+ sunscreen on the back with the help of a family member or friend.

If there is no one else around to help apply sunscreen on the back, Dr. Vincent A. DeLeo, Cutis Editor-in-Chief, suggests using spray sunscreens that work when held in an upside-down position or applying sunscreen to gauze or a cloth pad that can be attached to a back scratcher or wooden spoon to act as an extension of the arm. Photoprotective clothing also is important, according to Dr. DeLeo. “It doesn’t have to be specially made clothing. Just a T-shirt with a close weave. Hold it up to the light, and if you can’t see light through it, it will probably block UV rays,” he notes.

Throughout the year, remind your patients to watch their back. Share the new AAD infographic with them, which can be obtained on the AAD Web site.

The first-in-class immunotherapy IMCgp100 was active in late-stage melanoma, particularly ocular melanoma, in an ongoing, phase I/IIa trial.

Four of 14 patients treated with a weekly regimen in the phase IIa portion of the trial had a partial or complete response by RECIST 1.1, including two partial responses persisting more than 18 months.

© 2015 AACR/Todd Buchanan

Responses were observed across a variety of anatomical sites including liver and lung, and in patients refractory to ipilimumab (Yervoy) and pembrolizumab (Keytruda), “suggesting efficacy beyond the use of emerging and licensed treatments for melanoma,” principal investigator Dr. Mark Middleton said at the annual meeting of the American Association for Cancer Research.

The two shorter-lived responses – a partial response for 5.9 months and a complete response for 4.7 months – were in patients with ocular melanoma. One had been treated with surgery only, but the other had significant prior therapy and progressed through surgery, chemotherapy, radiation, and ipilimumab, he said. A third uveal melanoma patient left the trial after receiving what was later determined to be a nontolerated dose.

Progression-free survival in the two ocular melanoma responders was 9 months and 12 months, which bears up very well, compared with chemotherapy and data reported last year with MEK inhibition (JAMA 2014;311:2397-2405), said Dr. Middleton of the University of Oxford, England.

Invited discussant Dr. Antoni Ribas of the University of California Los Angeles Jonsson Comprehensive Cancer Center, commented that the responses were impressive.

“Anyone who’s treated ocular melanoma knows that if there’s a bad disease out there, this is one,” Dr. Ribas said. “It’s the subtype of melanoma that would not respond to any of the other immunotherapies and now we’re seeing responses here.”

The study enrolled patients with stage IV or unresectable stage III melanoma who were HLA-A2 (human leukocyte antigen-A2) positive and had no standard therapeutic options or had an appropriate window between alternative therapeutic options.

Patients had an ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1, three-fourths had M1c disease, and 16 had prior exposure to immunotherapy.

The phase I portion of the trial was designed to determine the maximum tolerated dose (MTD) of IMCgp100, with results reported at last year’s AACR.

IMCgp100 was dosed using a weekly regimen or a high-intensity regimen consisting of four consecutive daily doses in 3-week cycles. The maximum tolerated dose (MTD) for weekly administration was 600 nanograms/kilogram, which was converted to a flat dose of 50 mcg. Dose escalation of the high-intensity regimen is ongoing.

IMCgp100 contains an enhanced T-cell receptor and an anti-CD3 antibody fragment and is designed to redirect T cells to kill gp100-positive melanoma cells.

There is no clear correlation as yet between gp100 expression as measured by immunohistochemistry in the tumors because one patient who measured negative has a response at one of the lower dose levels, Dr. Middleton said.

“This isn’t a CLIA [Clinical Laboratory Improvement Amendments]-validated test, so the value of this, in particular, when taking relatively small samples is uncertain, and our working hypothesis has to be that gp100 expression is required in order to see an effective therapeutic response, albeit the ability to measure it remains uncertain,” he said.

Four dose-limiting toxicities, predominantly grade 3 or 4 hypotension, have been reported and emerged first at the 405 mg/kg dose. Most events resolved within 1-3 days.

One grade 4 hypotension was associated with associated acute respiratory distress syndrome and severe dyspnea in a patient on the MTD and resolved after intensive supportive care. With additional experience managing the potential for hypotension, however, there has been no significant hypotension at the MTD in the expansion phase, Dr. Middleton observed.

A phase 1b/II trial is being planned to evaluate IMCgp100 in combination with the anti–programmed death ligand-1 antibody MEDI4736 and/or the anti-CTLA-4 antibody tremelimumab in metastatic melanoma, according to a recent joint statement from Immunocore, developer of IMCgp100, and MedImmune.

[email protected]

On Twitter @pwendl

The first-in-class immunotherapy IMCgp100 was active in late-stage melanoma, particularly ocular melanoma, in an ongoing, phase I/IIa trial.

Four of 14 patients treated with a weekly regimen in the phase IIa portion of the trial had a partial or complete response by RECIST 1.1, including two partial responses persisting more than 18 months.

© 2015 AACR/Todd Buchanan

Responses were observed across a variety of anatomical sites including liver and lung, and in patients refractory to ipilimumab (Yervoy) and pembrolizumab (Keytruda), “suggesting efficacy beyond the use of emerging and licensed treatments for melanoma,” principal investigator Dr. Mark Middleton said at the annual meeting of the American Association for Cancer Research.

The two shorter-lived responses – a partial response for 5.9 months and a complete response for 4.7 months – were in patients with ocular melanoma. One had been treated with surgery only, but the other had significant prior therapy and progressed through surgery, chemotherapy, radiation, and ipilimumab, he said. A third uveal melanoma patient left the trial after receiving what was later determined to be a nontolerated dose.

Progression-free survival in the two ocular melanoma responders was 9 months and 12 months, which bears up very well, compared with chemotherapy and data reported last year with MEK inhibition (JAMA 2014;311:2397-2405), said Dr. Middleton of the University of Oxford, England.

Invited discussant Dr. Antoni Ribas of the University of California Los Angeles Jonsson Comprehensive Cancer Center, commented that the responses were impressive.

“Anyone who’s treated ocular melanoma knows that if there’s a bad disease out there, this is one,” Dr. Ribas said. “It’s the subtype of melanoma that would not respond to any of the other immunotherapies and now we’re seeing responses here.”

The study enrolled patients with stage IV or unresectable stage III melanoma who were HLA-A2 (human leukocyte antigen-A2) positive and had no standard therapeutic options or had an appropriate window between alternative therapeutic options.

Patients had an ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1, three-fourths had M1c disease, and 16 had prior exposure to immunotherapy.

The phase I portion of the trial was designed to determine the maximum tolerated dose (MTD) of IMCgp100, with results reported at last year’s AACR.

IMCgp100 was dosed using a weekly regimen or a high-intensity regimen consisting of four consecutive daily doses in 3-week cycles. The maximum tolerated dose (MTD) for weekly administration was 600 nanograms/kilogram, which was converted to a flat dose of 50 mcg. Dose escalation of the high-intensity regimen is ongoing.

IMCgp100 contains an enhanced T-cell receptor and an anti-CD3 antibody fragment and is designed to redirect T cells to kill gp100-positive melanoma cells.

There is no clear correlation as yet between gp100 expression as measured by immunohistochemistry in the tumors because one patient who measured negative has a response at one of the lower dose levels, Dr. Middleton said.

“This isn’t a CLIA [Clinical Laboratory Improvement Amendments]-validated test, so the value of this, in particular, when taking relatively small samples is uncertain, and our working hypothesis has to be that gp100 expression is required in order to see an effective therapeutic response, albeit the ability to measure it remains uncertain,” he said.

Four dose-limiting toxicities, predominantly grade 3 or 4 hypotension, have been reported and emerged first at the 405 mg/kg dose. Most events resolved within 1-3 days.

One grade 4 hypotension was associated with associated acute respiratory distress syndrome and severe dyspnea in a patient on the MTD and resolved after intensive supportive care. With additional experience managing the potential for hypotension, however, there has been no significant hypotension at the MTD in the expansion phase, Dr. Middleton observed.

A phase 1b/II trial is being planned to evaluate IMCgp100 in combination with the anti–programmed death ligand-1 antibody MEDI4736 and/or the anti-CTLA-4 antibody tremelimumab in metastatic melanoma, according to a recent joint statement from Immunocore, developer of IMCgp100, and MedImmune.

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The first-in-class immunotherapy IMCgp100 was active in late-stage melanoma, particularly ocular melanoma, in an ongoing, phase I/IIa trial.

Four of 14 patients treated with a weekly regimen in the phase IIa portion of the trial had a partial or complete response by RECIST 1.1, including two partial responses persisting more than 18 months.

© 2015 AACR/Todd Buchanan

Responses were observed across a variety of anatomical sites including liver and lung, and in patients refractory to ipilimumab (Yervoy) and pembrolizumab (Keytruda), “suggesting efficacy beyond the use of emerging and licensed treatments for melanoma,” principal investigator Dr. Mark Middleton said at the annual meeting of the American Association for Cancer Research.

The two shorter-lived responses – a partial response for 5.9 months and a complete response for 4.7 months – were in patients with ocular melanoma. One had been treated with surgery only, but the other had significant prior therapy and progressed through surgery, chemotherapy, radiation, and ipilimumab, he said. A third uveal melanoma patient left the trial after receiving what was later determined to be a nontolerated dose.

Progression-free survival in the two ocular melanoma responders was 9 months and 12 months, which bears up very well, compared with chemotherapy and data reported last year with MEK inhibition (JAMA 2014;311:2397-2405), said Dr. Middleton of the University of Oxford, England.

Invited discussant Dr. Antoni Ribas of the University of California Los Angeles Jonsson Comprehensive Cancer Center, commented that the responses were impressive.

“Anyone who’s treated ocular melanoma knows that if there’s a bad disease out there, this is one,” Dr. Ribas said. “It’s the subtype of melanoma that would not respond to any of the other immunotherapies and now we’re seeing responses here.”

The study enrolled patients with stage IV or unresectable stage III melanoma who were HLA-A2 (human leukocyte antigen-A2) positive and had no standard therapeutic options or had an appropriate window between alternative therapeutic options.

Patients had an ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1, three-fourths had M1c disease, and 16 had prior exposure to immunotherapy.

The phase I portion of the trial was designed to determine the maximum tolerated dose (MTD) of IMCgp100, with results reported at last year’s AACR.

IMCgp100 was dosed using a weekly regimen or a high-intensity regimen consisting of four consecutive daily doses in 3-week cycles. The maximum tolerated dose (MTD) for weekly administration was 600 nanograms/kilogram, which was converted to a flat dose of 50 mcg. Dose escalation of the high-intensity regimen is ongoing.

IMCgp100 contains an enhanced T-cell receptor and an anti-CD3 antibody fragment and is designed to redirect T cells to kill gp100-positive melanoma cells.

There is no clear correlation as yet between gp100 expression as measured by immunohistochemistry in the tumors because one patient who measured negative has a response at one of the lower dose levels, Dr. Middleton said.

“This isn’t a CLIA [Clinical Laboratory Improvement Amendments]-validated test, so the value of this, in particular, when taking relatively small samples is uncertain, and our working hypothesis has to be that gp100 expression is required in order to see an effective therapeutic response, albeit the ability to measure it remains uncertain,” he said.

Four dose-limiting toxicities, predominantly grade 3 or 4 hypotension, have been reported and emerged first at the 405 mg/kg dose. Most events resolved within 1-3 days.

One grade 4 hypotension was associated with associated acute respiratory distress syndrome and severe dyspnea in a patient on the MTD and resolved after intensive supportive care. With additional experience managing the potential for hypotension, however, there has been no significant hypotension at the MTD in the expansion phase, Dr. Middleton observed.

A phase 1b/II trial is being planned to evaluate IMCgp100 in combination with the anti–programmed death ligand-1 antibody MEDI4736 and/or the anti-CTLA-4 antibody tremelimumab in metastatic melanoma, according to a recent joint statement from Immunocore, developer of IMCgp100, and MedImmune.

[email protected]

On Twitter @pwendl

SILVER SPRING, MD. – A Food and Drug Administration advisory panel supports approval of talimogene laherparepvec (T-VEC), an oncolytic immunotherapy, voting 22-1 that the overall risk-benefit profile is favorable for treatment of patients with injectable regionally or distantly metastatic melanoma.

At a joint meeting of the FDA’s Oncologic Drugs Advisory Committee and the Cellular, Tissue and Gene Therapies Advisory Committee on April 29, panelists agreed that it was clear that at least some subpopulations of patients can benefit from this treatment, but cautioned that while nonvisceral metastases may respond to treatment, it was not clear whether visceral metastases responded, and that it should not be used to treat visceral disease. They also recommended that labeling should discourage clinicians from using this treatment in patients with substantial metastatic disease.

T-VEC is a first-in-class oncolytic immunotherapy derived from herpes simplex virus type 1 (HSV-1) the virus that causes most cold sores. It has been genetically modified to attenuate its virulence and engineered to express granulocyte-macrophage colony-stimulating factor (GM-CSF), while remaining susceptible to antiviral treatments such as acyclovir. T-VEC is injected directly into cutaneous, subcutaneous, or nodal lesions, “resulting in selective lysis of the injected tumor cells (and not normal tissue),” which “results in the release and presentation of tumor-derived antigens and local expression of GM-CSF to initiate a systemic anti-tumor immune response that also induces regression of non-injected and distant lesions,” according to the Amgen briefing documents. If approved, this would be the first virus-based cancer treatment, the company noted.

The FDA panel looked at a phase III, open-label, multicenter randomized study that compared treatment with T-VEC to GM-CSF (administered subcutaneously) in 436 people with melanoma (stage IIIB/C or stage IV with limited visceral disease burden that was considered unresectable); the trial began before several targeted and biologic treatments that are now available for advanced melanoma were approved. About half the patients had been treated previously for melanoma and more than 20% were older than 75 years; 292 patients were treated with T-VEC (up to 4 mL injected into one or more subcutaneous or nodal melanoma lesions every 1 or 2 weeks until clinically relevant disease progression occurred or there was no more residual tumor to inject) and 141 received GM-CSF daily in the control arm (for 14 days and off for 14 days).

The primary efficacy endpoint was the durable response rate (DRR), defined as the proportion of patients with responses (complete or partial) “maintained continuously for 6 or more months and beginning at any point within 12 months of initiating therapy,” as assessed by a blinded independent committee. That endpoint was met by 16.3% of those treated with T-VEC vs. 2.1% of those on GM-CSF, a significant difference (P < .0001).

Other results included the overall response rate – complete or partial – which was 26.4% in the T-VEC group vs. 5.7% in the control group; Complete response was 10.8% among those on T-VEC, vs. 0.7% among those on GM-CSF.

Among the approximately 400 patients treated with T-VEC in this and five other studies, the most common adverse events were expected, namely, cellulitis and flu-like symptoms, and most adverse events were mild or moderate.

Disease progression and cellulitis were the most common serious adverse events and occurred more often among those on T-VEC (3.1% vs. 1.6%, and 2.4% vs. 0.8%, respectively). Fatal adverse events were higher among those on T-VEC (3.4% vs. 1.6%); disease progression was the most commonly reported.

Almost 6% of those on T-VEC reported herpetic events, mostly oral herpes, but there were no serious herpes complications or cases of secondary transmission. Amgen has proposed a risk management plan to address the risks of the treatment, including herpetic lesions, accidental exposures to health care professionals, and secondary transmission, and postmarketing studies.

Several panelists pointed out that the company‘s claims that T-VEC has a systemic effect was not necessarily substantiated by the data, and that the unresectable disease qualifier should be added to the indication. Other points made by panel members were that the dosing instructions were not sufficient, and that while the safety profile was acceptable, the risks of cellulitis and of shedding on family members, pregnant women, children, health care professionals, and other cancer patients were concerns. Panelists also noted that it is unclear how T-VEC compares to the other treatments that have been approved for advanced melanoma over the past several years.

“What’s very, very clear is there is a response of the injected lesions.” and local control of lesions is important to patients, said panelist Dr. Patrick Hwu, professor in the department of melanoma medical oncology, University of Texas M.D. Anderson Cancer Center, Houston. Based on the data, “this clearly ... will be among the least toxic agents for cancer given in the [melanoma] clinic,” compared to other treatments, he added.

The FDA usually follows advisory panels’ recommendations. An FDA decision on approval is expected by Oct. 27, 2015, according to Amgen. Panelists had no potential conflicts of interest related to this meeting.

[email protected]

SILVER SPRING, MD. – A Food and Drug Administration advisory panel supports approval of talimogene laherparepvec (T-VEC), an oncolytic immunotherapy, voting 22-1 that the overall risk-benefit profile is favorable for treatment of patients with injectable regionally or distantly metastatic melanoma.

At a joint meeting of the FDA’s Oncologic Drugs Advisory Committee and the Cellular, Tissue and Gene Therapies Advisory Committee on April 29, panelists agreed that it was clear that at least some subpopulations of patients can benefit from this treatment, but cautioned that while nonvisceral metastases may respond to treatment, it was not clear whether visceral metastases responded, and that it should not be used to treat visceral disease. They also recommended that labeling should discourage clinicians from using this treatment in patients with substantial metastatic disease.

T-VEC is a first-in-class oncolytic immunotherapy derived from herpes simplex virus type 1 (HSV-1) the virus that causes most cold sores. It has been genetically modified to attenuate its virulence and engineered to express granulocyte-macrophage colony-stimulating factor (GM-CSF), while remaining susceptible to antiviral treatments such as acyclovir. T-VEC is injected directly into cutaneous, subcutaneous, or nodal lesions, “resulting in selective lysis of the injected tumor cells (and not normal tissue),” which “results in the release and presentation of tumor-derived antigens and local expression of GM-CSF to initiate a systemic anti-tumor immune response that also induces regression of non-injected and distant lesions,” according to the Amgen briefing documents. If approved, this would be the first virus-based cancer treatment, the company noted.

The FDA panel looked at a phase III, open-label, multicenter randomized study that compared treatment with T-VEC to GM-CSF (administered subcutaneously) in 436 people with melanoma (stage IIIB/C or stage IV with limited visceral disease burden that was considered unresectable); the trial began before several targeted and biologic treatments that are now available for advanced melanoma were approved. About half the patients had been treated previously for melanoma and more than 20% were older than 75 years; 292 patients were treated with T-VEC (up to 4 mL injected into one or more subcutaneous or nodal melanoma lesions every 1 or 2 weeks until clinically relevant disease progression occurred or there was no more residual tumor to inject) and 141 received GM-CSF daily in the control arm (for 14 days and off for 14 days).

The primary efficacy endpoint was the durable response rate (DRR), defined as the proportion of patients with responses (complete or partial) “maintained continuously for 6 or more months and beginning at any point within 12 months of initiating therapy,” as assessed by a blinded independent committee. That endpoint was met by 16.3% of those treated with T-VEC vs. 2.1% of those on GM-CSF, a significant difference (P < .0001).

Other results included the overall response rate – complete or partial – which was 26.4% in the T-VEC group vs. 5.7% in the control group; Complete response was 10.8% among those on T-VEC, vs. 0.7% among those on GM-CSF.

Among the approximately 400 patients treated with T-VEC in this and five other studies, the most common adverse events were expected, namely, cellulitis and flu-like symptoms, and most adverse events were mild or moderate.

Disease progression and cellulitis were the most common serious adverse events and occurred more often among those on T-VEC (3.1% vs. 1.6%, and 2.4% vs. 0.8%, respectively). Fatal adverse events were higher among those on T-VEC (3.4% vs. 1.6%); disease progression was the most commonly reported.

Almost 6% of those on T-VEC reported herpetic events, mostly oral herpes, but there were no serious herpes complications or cases of secondary transmission. Amgen has proposed a risk management plan to address the risks of the treatment, including herpetic lesions, accidental exposures to health care professionals, and secondary transmission, and postmarketing studies.

Several panelists pointed out that the company‘s claims that T-VEC has a systemic effect was not necessarily substantiated by the data, and that the unresectable disease qualifier should be added to the indication. Other points made by panel members were that the dosing instructions were not sufficient, and that while the safety profile was acceptable, the risks of cellulitis and of shedding on family members, pregnant women, children, health care professionals, and other cancer patients were concerns. Panelists also noted that it is unclear how T-VEC compares to the other treatments that have been approved for advanced melanoma over the past several years.

“What’s very, very clear is there is a response of the injected lesions.” and local control of lesions is important to patients, said panelist Dr. Patrick Hwu, professor in the department of melanoma medical oncology, University of Texas M.D. Anderson Cancer Center, Houston. Based on the data, “this clearly ... will be among the least toxic agents for cancer given in the [melanoma] clinic,” compared to other treatments, he added.

The FDA usually follows advisory panels’ recommendations. An FDA decision on approval is expected by Oct. 27, 2015, according to Amgen. Panelists had no potential conflicts of interest related to this meeting.

[email protected]

SILVER SPRING, MD. – A Food and Drug Administration advisory panel supports approval of talimogene laherparepvec (T-VEC), an oncolytic immunotherapy, voting 22-1 that the overall risk-benefit profile is favorable for treatment of patients with injectable regionally or distantly metastatic melanoma.

At a joint meeting of the FDA’s Oncologic Drugs Advisory Committee and the Cellular, Tissue and Gene Therapies Advisory Committee on April 29, panelists agreed that it was clear that at least some subpopulations of patients can benefit from this treatment, but cautioned that while nonvisceral metastases may respond to treatment, it was not clear whether visceral metastases responded, and that it should not be used to treat visceral disease. They also recommended that labeling should discourage clinicians from using this treatment in patients with substantial metastatic disease.

T-VEC is a first-in-class oncolytic immunotherapy derived from herpes simplex virus type 1 (HSV-1) the virus that causes most cold sores. It has been genetically modified to attenuate its virulence and engineered to express granulocyte-macrophage colony-stimulating factor (GM-CSF), while remaining susceptible to antiviral treatments such as acyclovir. T-VEC is injected directly into cutaneous, subcutaneous, or nodal lesions, “resulting in selective lysis of the injected tumor cells (and not normal tissue),” which “results in the release and presentation of tumor-derived antigens and local expression of GM-CSF to initiate a systemic anti-tumor immune response that also induces regression of non-injected and distant lesions,” according to the Amgen briefing documents. If approved, this would be the first virus-based cancer treatment, the company noted.

The FDA panel looked at a phase III, open-label, multicenter randomized study that compared treatment with T-VEC to GM-CSF (administered subcutaneously) in 436 people with melanoma (stage IIIB/C or stage IV with limited visceral disease burden that was considered unresectable); the trial began before several targeted and biologic treatments that are now available for advanced melanoma were approved. About half the patients had been treated previously for melanoma and more than 20% were older than 75 years; 292 patients were treated with T-VEC (up to 4 mL injected into one or more subcutaneous or nodal melanoma lesions every 1 or 2 weeks until clinically relevant disease progression occurred or there was no more residual tumor to inject) and 141 received GM-CSF daily in the control arm (for 14 days and off for 14 days).

The primary efficacy endpoint was the durable response rate (DRR), defined as the proportion of patients with responses (complete or partial) “maintained continuously for 6 or more months and beginning at any point within 12 months of initiating therapy,” as assessed by a blinded independent committee. That endpoint was met by 16.3% of those treated with T-VEC vs. 2.1% of those on GM-CSF, a significant difference (P < .0001).

Other results included the overall response rate – complete or partial – which was 26.4% in the T-VEC group vs. 5.7% in the control group; Complete response was 10.8% among those on T-VEC, vs. 0.7% among those on GM-CSF.

Among the approximately 400 patients treated with T-VEC in this and five other studies, the most common adverse events were expected, namely, cellulitis and flu-like symptoms, and most adverse events were mild or moderate.

Disease progression and cellulitis were the most common serious adverse events and occurred more often among those on T-VEC (3.1% vs. 1.6%, and 2.4% vs. 0.8%, respectively). Fatal adverse events were higher among those on T-VEC (3.4% vs. 1.6%); disease progression was the most commonly reported.

Almost 6% of those on T-VEC reported herpetic events, mostly oral herpes, but there were no serious herpes complications or cases of secondary transmission. Amgen has proposed a risk management plan to address the risks of the treatment, including herpetic lesions, accidental exposures to health care professionals, and secondary transmission, and postmarketing studies.

Several panelists pointed out that the company‘s claims that T-VEC has a systemic effect was not necessarily substantiated by the data, and that the unresectable disease qualifier should be added to the indication. Other points made by panel members were that the dosing instructions were not sufficient, and that while the safety profile was acceptable, the risks of cellulitis and of shedding on family members, pregnant women, children, health care professionals, and other cancer patients were concerns. Panelists also noted that it is unclear how T-VEC compares to the other treatments that have been approved for advanced melanoma over the past several years.

“What’s very, very clear is there is a response of the injected lesions.” and local control of lesions is important to patients, said panelist Dr. Patrick Hwu, professor in the department of melanoma medical oncology, University of Texas M.D. Anderson Cancer Center, Houston. Based on the data, “this clearly ... will be among the least toxic agents for cancer given in the [melanoma] clinic,” compared to other treatments, he added.

The FDA usually follows advisory panels’ recommendations. An FDA decision on approval is expected by Oct. 27, 2015, according to Amgen. Panelists had no potential conflicts of interest related to this meeting.

[email protected]