[HTML][HTML] Talimogene laherparepvec improves durable response rate in patients with advanced melanoma

RHI Andtbacka, HL Kaufman, F Collichio… - Journal of clinical …, 2015 - iro.uiowa.edu
RHI Andtbacka, HL Kaufman, F Collichio, T Amatruda, N Senzer, J Chesney, KA Delman…
Journal of clinical oncology, 2015iro.uiowa.edu
Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic
immunotherapy designed to selectively replicate within tumors and produce granulocyte
macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune
responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV
melanoma in a randomized open-label phase III trial. Patients with injectable melanoma that
was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T …
Abstract
Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial. Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously≥ 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate. Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P<. 001). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=. 051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in≥ 2% of T-VEC-treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred. T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P<. 001) and longer median OS (P=. 051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma.
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