Melanoma

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.

[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.

[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]

Clarke et al published a study online on March 2 in the Journal of Cutaneous Pathology regarding a novel diagnostic test for melanoma. Using quantitative reverse transcriptase–polymerase chain reaction targeting 23 preselected genes, biopsy samples from a variety of melanocytic skin lesions—464 lesions in a training set and 437 lesions in a separate validation set—were analyzed. The test assigned a single numeric score favoring either benign or malignant with sensitivity and specificity of 89% and 93%, respectively (training set), and 90% and 91%, respectively (validation set), when compared to expert consensus dermatopathology review.

What’s the issue?

Any clinician who biopsies multiple melanocytic lesions per day daydreams about a modality that will consistently and accurately distinguish the neoplasms that haunt us the most: the ones with no clear diagnosis and the lesions where intra- and interdepartmental histopathology results vary across the board. In fact, a patient recently told me that I “missed” her “dangerous” melanoma when our dermatopathology and outside consultant opinions stated that the lesion was a dysplastic nevus. The patient personally took the slides to another institution where they were deemed an “evolving” melanoma in situ. Are they all correct? How do we know that something is evolving? Which tumors will eventually be the sinister ones? If we don’t know, then how can a patient understand his/her predicament? What’s a clinician to do?

Reassuringly, in perusing the exhibit hall at the 73rd Annual Meeting of the American Academy of Dermatology, the climate has shifted somewhat. A new zone of molecular and genetic technology has emerged between the rows of pharmaceutical innovation and office supply hardware. The reverse transcriptase–polymerase chain reaction melanoma diagnostic test distinguishes itself with its large study set and measurement parameters, as it quantifies gene expression. Other adjunctive diagnostic modalities have been proven useful in atypical melanocytic proliferations, such as fluorescence in situ hybridization, comparative genomic hybridization, and DNA microarray technology, with focus on physical chromosomal copy alterations; however, it seems as though this new test provides a functional measure and straightforward plus/minus result that may be more universally and objectively relevant and interpretable from a simple skin biopsy. Perhaps the diagnostic technology has now outpaced our limited and confusing vocabulary for melanocytic lesions. Nonetheless, further clinical follow-up, prospective prognostic data, and cost analysis will define its evolving role. How do you think this gene signature test will ultimately influence our interpretation of melanocytic biopsy results?

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

Clarke et al published a study online on March 2 in the Journal of Cutaneous Pathology regarding a novel diagnostic test for melanoma. Using quantitative reverse transcriptase–polymerase chain reaction targeting 23 preselected genes, biopsy samples from a variety of melanocytic skin lesions—464 lesions in a training set and 437 lesions in a separate validation set—were analyzed. The test assigned a single numeric score favoring either benign or malignant with sensitivity and specificity of 89% and 93%, respectively (training set), and 90% and 91%, respectively (validation set), when compared to expert consensus dermatopathology review.

What’s the issue?

Any clinician who biopsies multiple melanocytic lesions per day daydreams about a modality that will consistently and accurately distinguish the neoplasms that haunt us the most: the ones with no clear diagnosis and the lesions where intra- and interdepartmental histopathology results vary across the board. In fact, a patient recently told me that I “missed” her “dangerous” melanoma when our dermatopathology and outside consultant opinions stated that the lesion was a dysplastic nevus. The patient personally took the slides to another institution where they were deemed an “evolving” melanoma in situ. Are they all correct? How do we know that something is evolving? Which tumors will eventually be the sinister ones? If we don’t know, then how can a patient understand his/her predicament? What’s a clinician to do?

Reassuringly, in perusing the exhibit hall at the 73rd Annual Meeting of the American Academy of Dermatology, the climate has shifted somewhat. A new zone of molecular and genetic technology has emerged between the rows of pharmaceutical innovation and office supply hardware. The reverse transcriptase–polymerase chain reaction melanoma diagnostic test distinguishes itself with its large study set and measurement parameters, as it quantifies gene expression. Other adjunctive diagnostic modalities have been proven useful in atypical melanocytic proliferations, such as fluorescence in situ hybridization, comparative genomic hybridization, and DNA microarray technology, with focus on physical chromosomal copy alterations; however, it seems as though this new test provides a functional measure and straightforward plus/minus result that may be more universally and objectively relevant and interpretable from a simple skin biopsy. Perhaps the diagnostic technology has now outpaced our limited and confusing vocabulary for melanocytic lesions. Nonetheless, further clinical follow-up, prospective prognostic data, and cost analysis will define its evolving role. How do you think this gene signature test will ultimately influence our interpretation of melanocytic biopsy results?

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

Clarke et al published a study online on March 2 in the Journal of Cutaneous Pathology regarding a novel diagnostic test for melanoma. Using quantitative reverse transcriptase–polymerase chain reaction targeting 23 preselected genes, biopsy samples from a variety of melanocytic skin lesions—464 lesions in a training set and 437 lesions in a separate validation set—were analyzed. The test assigned a single numeric score favoring either benign or malignant with sensitivity and specificity of 89% and 93%, respectively (training set), and 90% and 91%, respectively (validation set), when compared to expert consensus dermatopathology review.

What’s the issue?

Any clinician who biopsies multiple melanocytic lesions per day daydreams about a modality that will consistently and accurately distinguish the neoplasms that haunt us the most: the ones with no clear diagnosis and the lesions where intra- and interdepartmental histopathology results vary across the board. In fact, a patient recently told me that I “missed” her “dangerous” melanoma when our dermatopathology and outside consultant opinions stated that the lesion was a dysplastic nevus. The patient personally took the slides to another institution where they were deemed an “evolving” melanoma in situ. Are they all correct? How do we know that something is evolving? Which tumors will eventually be the sinister ones? If we don’t know, then how can a patient understand his/her predicament? What’s a clinician to do?

Reassuringly, in perusing the exhibit hall at the 73rd Annual Meeting of the American Academy of Dermatology, the climate has shifted somewhat. A new zone of molecular and genetic technology has emerged between the rows of pharmaceutical innovation and office supply hardware. The reverse transcriptase–polymerase chain reaction melanoma diagnostic test distinguishes itself with its large study set and measurement parameters, as it quantifies gene expression. Other adjunctive diagnostic modalities have been proven useful in atypical melanocytic proliferations, such as fluorescence in situ hybridization, comparative genomic hybridization, and DNA microarray technology, with focus on physical chromosomal copy alterations; however, it seems as though this new test provides a functional measure and straightforward plus/minus result that may be more universally and objectively relevant and interpretable from a simple skin biopsy. Perhaps the diagnostic technology has now outpaced our limited and confusing vocabulary for melanocytic lesions. Nonetheless, further clinical follow-up, prospective prognostic data, and cost analysis will define its evolving role. How do you think this gene signature test will ultimately influence our interpretation of melanocytic biopsy results?

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

KISSIMMEE, FLA. – Using a needle-free device to inject nodular basal cell carcinomas with intralesional 5-aminolevulinic acid before photodynamic therapy led to complete, years-long remissions and few side effects in a small case series.

“This approach represents an interesting alternative to Mohs, for sure,” Dr. Daniel Barolet said at the annual meeting of the American Society for Laser Medicine and Surgery. “The secret is in the injector nozzle, which lets you inject with multiple openings to get the best uniformity around the tumor.”

Mohs micrographic surgery remains the standard for basal cell carcinoma (BCC) in high-risk sites, and the number of Mohs surgeries has approximately doubled since 2001, said Dr. Barolet, adjunct professor of dermatology at McGill University in Montreal.

Mohs, however, can cause scarring, and BCCs recur in about 4% of patients. In contrast, photodynamic therapy (PDT) is associated with less scarring and pain, fewer complications, shorter recovery times, and lower costs, although the recurrence rate is about 14%, he noted.

Since PDT alone does not efficiently penetrate thick tumor volumes, it works best with pretreatment using agents such as aminolevulinic acid (ALA).

Using needles to inject the tumor, however, can cause pain, vascular damage, vasoconstriction, deep purpura, necrosis, and infection. “Because of this, no-needle injection is an interesting avenue for PDT,” he noted. Needle-free devices currently are used to inject insulin and to administer some vaccines. They are “virtually painless,” noninvasive, and tissue sparing, he said.

To explore the potential role for needle-free injection in ALA-PDT, Dr. Barolot used a prototype high-speed jet to deliver intralesional 5-ALA in the nodular facial BCCs of four patients. He then performed photoactivation with a red light–emitting diode, with continuous wave at 630 nm, irradiance at 50 mW/cm², and total fluence 50-100 J/cm².

Patients had no evidence of clinical or histopathologic recurrence for up to 7 years after treatment, Dr. Barolet reported. They experienced mild crusting at treated sites for up to a week after treatment, but no other adverse effects. Two patients needed a second treatment 2 months after the initial treatment to achieve complete remission. “Excellent cosmesis was obtained,” he added, pointing to before and after photos that showed no evidence of lesions several months after treatment.

Multicenter clinical trials are needed to further evaluate the modality, but the preliminary data suggest that intralesional PDT is a reasonable alternative to Mohs for BCCs in high-risk body sites, as long as lesions are few in number and do not affect large areas of the body, Dr. Barolet said.

The modality is especially well suited to “tricky” areas of the body that are difficult to treat with Mohs, he said.

“Developing a user-friendly, disposable no-needle injector will make it much easier for users,” he added. For low-risk BCCs in low-risk sites, conventional treatments such as surgical excision remain the best option, he said.

Dr. Barolet reported no funding sources for the study and said he had no relevant financial disclosures.

KISSIMMEE, FLA. – Using a needle-free device to inject nodular basal cell carcinomas with intralesional 5-aminolevulinic acid before photodynamic therapy led to complete, years-long remissions and few side effects in a small case series.

“This approach represents an interesting alternative to Mohs, for sure,” Dr. Daniel Barolet said at the annual meeting of the American Society for Laser Medicine and Surgery. “The secret is in the injector nozzle, which lets you inject with multiple openings to get the best uniformity around the tumor.”

Mohs micrographic surgery remains the standard for basal cell carcinoma (BCC) in high-risk sites, and the number of Mohs surgeries has approximately doubled since 2001, said Dr. Barolet, adjunct professor of dermatology at McGill University in Montreal.

Mohs, however, can cause scarring, and BCCs recur in about 4% of patients. In contrast, photodynamic therapy (PDT) is associated with less scarring and pain, fewer complications, shorter recovery times, and lower costs, although the recurrence rate is about 14%, he noted.

Since PDT alone does not efficiently penetrate thick tumor volumes, it works best with pretreatment using agents such as aminolevulinic acid (ALA).

Using needles to inject the tumor, however, can cause pain, vascular damage, vasoconstriction, deep purpura, necrosis, and infection. “Because of this, no-needle injection is an interesting avenue for PDT,” he noted. Needle-free devices currently are used to inject insulin and to administer some vaccines. They are “virtually painless,” noninvasive, and tissue sparing, he said.

To explore the potential role for needle-free injection in ALA-PDT, Dr. Barolot used a prototype high-speed jet to deliver intralesional 5-ALA in the nodular facial BCCs of four patients. He then performed photoactivation with a red light–emitting diode, with continuous wave at 630 nm, irradiance at 50 mW/cm², and total fluence 50-100 J/cm².

Patients had no evidence of clinical or histopathologic recurrence for up to 7 years after treatment, Dr. Barolet reported. They experienced mild crusting at treated sites for up to a week after treatment, but no other adverse effects. Two patients needed a second treatment 2 months after the initial treatment to achieve complete remission. “Excellent cosmesis was obtained,” he added, pointing to before and after photos that showed no evidence of lesions several months after treatment.

Multicenter clinical trials are needed to further evaluate the modality, but the preliminary data suggest that intralesional PDT is a reasonable alternative to Mohs for BCCs in high-risk body sites, as long as lesions are few in number and do not affect large areas of the body, Dr. Barolet said.

The modality is especially well suited to “tricky” areas of the body that are difficult to treat with Mohs, he said.

“Developing a user-friendly, disposable no-needle injector will make it much easier for users,” he added. For low-risk BCCs in low-risk sites, conventional treatments such as surgical excision remain the best option, he said.

Dr. Barolet reported no funding sources for the study and said he had no relevant financial disclosures.

KISSIMMEE, FLA. – Using a needle-free device to inject nodular basal cell carcinomas with intralesional 5-aminolevulinic acid before photodynamic therapy led to complete, years-long remissions and few side effects in a small case series.

“This approach represents an interesting alternative to Mohs, for sure,” Dr. Daniel Barolet said at the annual meeting of the American Society for Laser Medicine and Surgery. “The secret is in the injector nozzle, which lets you inject with multiple openings to get the best uniformity around the tumor.”

Mohs micrographic surgery remains the standard for basal cell carcinoma (BCC) in high-risk sites, and the number of Mohs surgeries has approximately doubled since 2001, said Dr. Barolet, adjunct professor of dermatology at McGill University in Montreal.

Mohs, however, can cause scarring, and BCCs recur in about 4% of patients. In contrast, photodynamic therapy (PDT) is associated with less scarring and pain, fewer complications, shorter recovery times, and lower costs, although the recurrence rate is about 14%, he noted.

Since PDT alone does not efficiently penetrate thick tumor volumes, it works best with pretreatment using agents such as aminolevulinic acid (ALA).

Using needles to inject the tumor, however, can cause pain, vascular damage, vasoconstriction, deep purpura, necrosis, and infection. “Because of this, no-needle injection is an interesting avenue for PDT,” he noted. Needle-free devices currently are used to inject insulin and to administer some vaccines. They are “virtually painless,” noninvasive, and tissue sparing, he said.

To explore the potential role for needle-free injection in ALA-PDT, Dr. Barolot used a prototype high-speed jet to deliver intralesional 5-ALA in the nodular facial BCCs of four patients. He then performed photoactivation with a red light–emitting diode, with continuous wave at 630 nm, irradiance at 50 mW/cm², and total fluence 50-100 J/cm².

Patients had no evidence of clinical or histopathologic recurrence for up to 7 years after treatment, Dr. Barolet reported. They experienced mild crusting at treated sites for up to a week after treatment, but no other adverse effects. Two patients needed a second treatment 2 months after the initial treatment to achieve complete remission. “Excellent cosmesis was obtained,” he added, pointing to before and after photos that showed no evidence of lesions several months after treatment.

Multicenter clinical trials are needed to further evaluate the modality, but the preliminary data suggest that intralesional PDT is a reasonable alternative to Mohs for BCCs in high-risk body sites, as long as lesions are few in number and do not affect large areas of the body, Dr. Barolet said.

The modality is especially well suited to “tricky” areas of the body that are difficult to treat with Mohs, he said.

“Developing a user-friendly, disposable no-needle injector will make it much easier for users,” he added. For low-risk BCCs in low-risk sites, conventional treatments such as surgical excision remain the best option, he said.

Dr. Barolet reported no funding sources for the study and said he had no relevant financial disclosures.

Of all drugs to be released in 2015, the melanoma drug Opdivo (nivolumab) is expected to have the brightest future, according to a report from Thomson Reuters.

With sales forecast to reach nearly $5.7 billion by 2019, Opdivo is at the head of a large 2015 “blockbuster” drug class. Opdivo is followed by a pair of drugs for the cardiovascular system: Praluent (alirocumab) for hypercholesterolemia with projected sales of $4.4 billion and LCZ-696 (sacubitril and valsartan) for chronic heart failure with projected 2019 sales of $3.7 billion, Thomson Reuters said.

With estimated sales of $2.8 billion, the breast cancer drug Ibrance (palbociclib) is the second oncologic drug making the blockbuster list, with the first noncancer or non-CV drug – lumacaftor plus ivacaftor for cystic fibrosis – rounding out the Top 5 with projected sales of $2.7 billion by 2019.

Next comes Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets, copackaged with dasabuvir tablets), a hepatitis C virus drug with estimated 2019 sales of $2.5 billion, followed by the hypercholesterolemia/hyperlipidemia drug evolocumab, with projected sales of $1.9 billion. This $2.5 billion disparity between evolocumab and Praluent may be explained by Praluent’s arrival on the market a month sooner, and also because Praluent had a reduced rate of cardiac death, heart attack, and stroke in a phase III trial, a point likely to be relevant to most patients, according to the report.

Overall, 11 drugs are expected to reach $1 billion in sales by 2019, many more than the three blockbusters predicted from the 2014 stock of drugs. However, the two highest-selling new drugs from 2014, Sovaldi (sofosbuvir) and Harvoni (sofosbuvir plus ledipasvir) – both HCV drugs – are each predicted to reach sales of more than $10 billion by 2017, far exceeding anything from 2015, the report said.

The Thomson Reuters Market Insight Report used data collected from 2013 through early February 2015.

[email protected]

Of all drugs to be released in 2015, the melanoma drug Opdivo (nivolumab) is expected to have the brightest future, according to a report from Thomson Reuters.

With sales forecast to reach nearly $5.7 billion by 2019, Opdivo is at the head of a large 2015 “blockbuster” drug class. Opdivo is followed by a pair of drugs for the cardiovascular system: Praluent (alirocumab) for hypercholesterolemia with projected sales of $4.4 billion and LCZ-696 (sacubitril and valsartan) for chronic heart failure with projected 2019 sales of $3.7 billion, Thomson Reuters said.

With estimated sales of $2.8 billion, the breast cancer drug Ibrance (palbociclib) is the second oncologic drug making the blockbuster list, with the first noncancer or non-CV drug – lumacaftor plus ivacaftor for cystic fibrosis – rounding out the Top 5 with projected sales of $2.7 billion by 2019.

Next comes Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets, copackaged with dasabuvir tablets), a hepatitis C virus drug with estimated 2019 sales of $2.5 billion, followed by the hypercholesterolemia/hyperlipidemia drug evolocumab, with projected sales of $1.9 billion. This $2.5 billion disparity between evolocumab and Praluent may be explained by Praluent’s arrival on the market a month sooner, and also because Praluent had a reduced rate of cardiac death, heart attack, and stroke in a phase III trial, a point likely to be relevant to most patients, according to the report.

Overall, 11 drugs are expected to reach $1 billion in sales by 2019, many more than the three blockbusters predicted from the 2014 stock of drugs. However, the two highest-selling new drugs from 2014, Sovaldi (sofosbuvir) and Harvoni (sofosbuvir plus ledipasvir) – both HCV drugs – are each predicted to reach sales of more than $10 billion by 2017, far exceeding anything from 2015, the report said.

The Thomson Reuters Market Insight Report used data collected from 2013 through early February 2015.

[email protected]

Of all drugs to be released in 2015, the melanoma drug Opdivo (nivolumab) is expected to have the brightest future, according to a report from Thomson Reuters.

With sales forecast to reach nearly $5.7 billion by 2019, Opdivo is at the head of a large 2015 “blockbuster” drug class. Opdivo is followed by a pair of drugs for the cardiovascular system: Praluent (alirocumab) for hypercholesterolemia with projected sales of $4.4 billion and LCZ-696 (sacubitril and valsartan) for chronic heart failure with projected 2019 sales of $3.7 billion, Thomson Reuters said.

With estimated sales of $2.8 billion, the breast cancer drug Ibrance (palbociclib) is the second oncologic drug making the blockbuster list, with the first noncancer or non-CV drug – lumacaftor plus ivacaftor for cystic fibrosis – rounding out the Top 5 with projected sales of $2.7 billion by 2019.

Next comes Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets, copackaged with dasabuvir tablets), a hepatitis C virus drug with estimated 2019 sales of $2.5 billion, followed by the hypercholesterolemia/hyperlipidemia drug evolocumab, with projected sales of $1.9 billion. This $2.5 billion disparity between evolocumab and Praluent may be explained by Praluent’s arrival on the market a month sooner, and also because Praluent had a reduced rate of cardiac death, heart attack, and stroke in a phase III trial, a point likely to be relevant to most patients, according to the report.

Overall, 11 drugs are expected to reach $1 billion in sales by 2019, many more than the three blockbusters predicted from the 2014 stock of drugs. However, the two highest-selling new drugs from 2014, Sovaldi (sofosbuvir) and Harvoni (sofosbuvir plus ledipasvir) – both HCV drugs – are each predicted to reach sales of more than $10 billion by 2017, far exceeding anything from 2015, the report said.

The Thomson Reuters Market Insight Report used data collected from 2013 through early February 2015.

[email protected]