Author(s): Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N,
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Abstract PURPOSE: 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 AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00769704. © 2015 by American Society of Clinical Oncology.
This article was published in J Clin Oncol
and referenced in Immunotherapy: Open Access