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Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma
Journal article   Peer reviewed

Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

Robert H I Andtbacka, Howard L Kaufman, Frances Collichio, Thomas Amatruda, Neil Senzer, Jason Chesney, Keith A Delman, Lynn E Spitler, Igor Puzanov, Sanjiv S Agarwala, …
Journal of clinical oncology, Vol.33(25), pp.2780-2788
09/01/2015
DOI: 10.1200/JCO.2014.58.3377
PMID: 26014293

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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.
 Adjuvants, Immunologic - administration & dosage Adjuvants, Immunologic - adverse effects Adjuvants, Immunologic - therapeutic use Adult Aged Aged, 80 and over Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Antineoplastic Agents - therapeutic use Chills - chemically induced Fatigue - chemically induced Female Fever - chemically induced Granulocyte-Macrophage Colony-Stimulating Factor - drug effects Granulocyte-Macrophage Colony-Stimulating Factor - immunology Herpesvirus 1, Human Humans Immunotherapy - methods Injections, Intralesional Male Melanoma - drug therapy Melanoma - immunology Melanoma - mortality Melanoma - prevention & control Melanoma - secondary Middle Aged Neoplasm Staging Odds Ratio Oncolytic Virotherapy Oncolytic Viruses Skin Neoplasms - drug therapy Skin Neoplasms - immunology Skin Neoplasms - mortality Skin Neoplasms - pathology Skin Neoplasms - prevention & control Survival Analysis Time Factors Treatment Outcome United States - epidemiology

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