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Following a phase III, open-label trial conducted by Andtbacka et al (J Clin Oncol. 2015;33:2780-2788), the US Food and Drug Administration recently approved the first oncolytic immunotherapy talimogene laherparepvec (T-VEC) for the treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with advanced melanoma (stage IIIB/C–stage IV) following initial surgery.
A group of 436 patients with injectable melanomas (melanomas that are accessible via a percutaneous injection) that were not surgically resectable were randomly assigned (2:1) to treatment with intralesional T-VEC or subcutaneous granulocyte macrophage colony-stimulating factor (GM-CSF). The primary endpoint of the study was durable response rate (DRR), defined as objective response lasting continuously for 6 months or longer. Secondary endpoints included overall survival (OS) and overall response rate.
Talimogene laherparepvec was shown to extend DRRs compared to GM-CSF. Durable response rates were significantly higher with T-VEC (16.3%; 95% confidence interval [CI], 12.1%–20.5%) versus GM-CSF (2.1%; 95% CI, 0%–4.5%)(odds ratio, 8.9; P<.001).
In the OS analysis, a 4.4-month extension with T-VEC was observed; however, this was not deemed to be statistically significant (P=.051). The median OS was 23.3 months (95% CI, 19.5–29.6 months) with T-VEC and 18.9 months (95% CI, 16.0–23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62–1.00; P=.051). Overall response rate also was higher in the T-VEC arm (26.4%; 95% CI, 21.4%–31.5%) versus GM-CSF (5.7%; 95% CI, 1.9%–9.5%).
Talimogene laherparepvec is a herpes simplex virus type 1–derived oncolytic immunotherapy designed to replicate within tumors and produce GM-CSF, which enhances systemic antitumor immune responses and induces tumor lysis.
In this study, T-VEC efficacy was greatest in patients with stage IIIB, IIIC, or IVM1a melanomas and in patients with treatment-naive disease. Differences in DRRs in patients with stage IIIB/C melanomas were 33% in the T-VEC group versus 0% for patients treated with GM-CSF alone. In the stage IVM1a group, DRR was 16% with T-VEC versus 2% with GM-CSF. The difference between both treatments was smaller in more advanced melanomas (IVM1b group, 3% vs 4%; IVM1c, 7% vs 3%). In the first-line treatment, the DRR with T-VEC was 24% versus 0% with GM-CSF. In the second-line and beyond, the DRR with T-VEC was 10% compared to 4% for GM-CSF.
The main adverse events seen in this study were fatigue, chills, and pyrexia. Serious adverse events occurred in 25.7% and 13.4% of participants in the T-VEC and GM-CSF arms, respectively, with disease progression (3.1% vs 1.6%) and cellulitis (2.4% vs 0.8%) being the most common. Six immune-mediated events occurred in the T-VEC group compared to 3 in the GM-CSF group.
Twelve patient deaths occurred within 30 days of the last dose of T-VEC; 9 were associated with progressive disease and the other 3 were associated with myocardial infarction, cardiac arrest, and sepsis, respectively. Four patient deaths were reported in the GM-CSF arm within the same 30 days.
What’s the Issue?
Immunotherapy represents a promising treatment option for metastatic melanoma. These promising results along with the US Food and Drug Administration’s approval of T-VEC will lead to further studies of the uses of T-VEC in combination with other therapies, including a phase I/II study to assess T-VEC in combination with ipilimumab for unresected melanomas (NCT01740297) and a phase III study of T-VEC in combination with pembrolizumab for unresected melanomas (NCT02263508). It is important for dermatologists to be familiar with the new frontier of melanoma treatments. How will these new immunotherapies affect your treatment of melanoma?
Following a phase III, open-label trial conducted by Andtbacka et al (J Clin Oncol. 2015;33:2780-2788), the US Food and Drug Administration recently approved the first oncolytic immunotherapy talimogene laherparepvec (T-VEC) for the treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with advanced melanoma (stage IIIB/C–stage IV) following initial surgery.
A group of 436 patients with injectable melanomas (melanomas that are accessible via a percutaneous injection) that were not surgically resectable were randomly assigned (2:1) to treatment with intralesional T-VEC or subcutaneous granulocyte macrophage colony-stimulating factor (GM-CSF). The primary endpoint of the study was durable response rate (DRR), defined as objective response lasting continuously for 6 months or longer. Secondary endpoints included overall survival (OS) and overall response rate.
Talimogene laherparepvec was shown to extend DRRs compared to GM-CSF. Durable response rates were significantly higher with T-VEC (16.3%; 95% confidence interval [CI], 12.1%–20.5%) versus GM-CSF (2.1%; 95% CI, 0%–4.5%)(odds ratio, 8.9; P<.001).
In the OS analysis, a 4.4-month extension with T-VEC was observed; however, this was not deemed to be statistically significant (P=.051). The median OS was 23.3 months (95% CI, 19.5–29.6 months) with T-VEC and 18.9 months (95% CI, 16.0–23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62–1.00; P=.051). Overall response rate also was higher in the T-VEC arm (26.4%; 95% CI, 21.4%–31.5%) versus GM-CSF (5.7%; 95% CI, 1.9%–9.5%).
Talimogene laherparepvec is a herpes simplex virus type 1–derived oncolytic immunotherapy designed to replicate within tumors and produce GM-CSF, which enhances systemic antitumor immune responses and induces tumor lysis.
In this study, T-VEC efficacy was greatest in patients with stage IIIB, IIIC, or IVM1a melanomas and in patients with treatment-naive disease. Differences in DRRs in patients with stage IIIB/C melanomas were 33% in the T-VEC group versus 0% for patients treated with GM-CSF alone. In the stage IVM1a group, DRR was 16% with T-VEC versus 2% with GM-CSF. The difference between both treatments was smaller in more advanced melanomas (IVM1b group, 3% vs 4%; IVM1c, 7% vs 3%). In the first-line treatment, the DRR with T-VEC was 24% versus 0% with GM-CSF. In the second-line and beyond, the DRR with T-VEC was 10% compared to 4% for GM-CSF.
The main adverse events seen in this study were fatigue, chills, and pyrexia. Serious adverse events occurred in 25.7% and 13.4% of participants in the T-VEC and GM-CSF arms, respectively, with disease progression (3.1% vs 1.6%) and cellulitis (2.4% vs 0.8%) being the most common. Six immune-mediated events occurred in the T-VEC group compared to 3 in the GM-CSF group.
Twelve patient deaths occurred within 30 days of the last dose of T-VEC; 9 were associated with progressive disease and the other 3 were associated with myocardial infarction, cardiac arrest, and sepsis, respectively. Four patient deaths were reported in the GM-CSF arm within the same 30 days.
What’s the Issue?
Immunotherapy represents a promising treatment option for metastatic melanoma. These promising results along with the US Food and Drug Administration’s approval of T-VEC will lead to further studies of the uses of T-VEC in combination with other therapies, including a phase I/II study to assess T-VEC in combination with ipilimumab for unresected melanomas (NCT01740297) and a phase III study of T-VEC in combination with pembrolizumab for unresected melanomas (NCT02263508). It is important for dermatologists to be familiar with the new frontier of melanoma treatments. How will these new immunotherapies affect your treatment of melanoma?
Following a phase III, open-label trial conducted by Andtbacka et al (J Clin Oncol. 2015;33:2780-2788), the US Food and Drug Administration recently approved the first oncolytic immunotherapy talimogene laherparepvec (T-VEC) for the treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with advanced melanoma (stage IIIB/C–stage IV) following initial surgery.
A group of 436 patients with injectable melanomas (melanomas that are accessible via a percutaneous injection) that were not surgically resectable were randomly assigned (2:1) to treatment with intralesional T-VEC or subcutaneous granulocyte macrophage colony-stimulating factor (GM-CSF). The primary endpoint of the study was durable response rate (DRR), defined as objective response lasting continuously for 6 months or longer. Secondary endpoints included overall survival (OS) and overall response rate.
Talimogene laherparepvec was shown to extend DRRs compared to GM-CSF. Durable response rates were significantly higher with T-VEC (16.3%; 95% confidence interval [CI], 12.1%–20.5%) versus GM-CSF (2.1%; 95% CI, 0%–4.5%)(odds ratio, 8.9; P<.001).
In the OS analysis, a 4.4-month extension with T-VEC was observed; however, this was not deemed to be statistically significant (P=.051). The median OS was 23.3 months (95% CI, 19.5–29.6 months) with T-VEC and 18.9 months (95% CI, 16.0–23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62–1.00; P=.051). Overall response rate also was higher in the T-VEC arm (26.4%; 95% CI, 21.4%–31.5%) versus GM-CSF (5.7%; 95% CI, 1.9%–9.5%).
Talimogene laherparepvec is a herpes simplex virus type 1–derived oncolytic immunotherapy designed to replicate within tumors and produce GM-CSF, which enhances systemic antitumor immune responses and induces tumor lysis.
In this study, T-VEC efficacy was greatest in patients with stage IIIB, IIIC, or IVM1a melanomas and in patients with treatment-naive disease. Differences in DRRs in patients with stage IIIB/C melanomas were 33% in the T-VEC group versus 0% for patients treated with GM-CSF alone. In the stage IVM1a group, DRR was 16% with T-VEC versus 2% with GM-CSF. The difference between both treatments was smaller in more advanced melanomas (IVM1b group, 3% vs 4%; IVM1c, 7% vs 3%). In the first-line treatment, the DRR with T-VEC was 24% versus 0% with GM-CSF. In the second-line and beyond, the DRR with T-VEC was 10% compared to 4% for GM-CSF.
The main adverse events seen in this study were fatigue, chills, and pyrexia. Serious adverse events occurred in 25.7% and 13.4% of participants in the T-VEC and GM-CSF arms, respectively, with disease progression (3.1% vs 1.6%) and cellulitis (2.4% vs 0.8%) being the most common. Six immune-mediated events occurred in the T-VEC group compared to 3 in the GM-CSF group.
Twelve patient deaths occurred within 30 days of the last dose of T-VEC; 9 were associated with progressive disease and the other 3 were associated with myocardial infarction, cardiac arrest, and sepsis, respectively. Four patient deaths were reported in the GM-CSF arm within the same 30 days.
What’s the Issue?
Immunotherapy represents a promising treatment option for metastatic melanoma. These promising results along with the US Food and Drug Administration’s approval of T-VEC will lead to further studies of the uses of T-VEC in combination with other therapies, including a phase I/II study to assess T-VEC in combination with ipilimumab for unresected melanomas (NCT01740297) and a phase III study of T-VEC in combination with pembrolizumab for unresected melanomas (NCT02263508). It is important for dermatologists to be familiar with the new frontier of melanoma treatments. How will these new immunotherapies affect your treatment of melanoma?
