Oncolytic Immunotherapy With Talimogene Laherparepvec Improves Durable Response Rate in Advanced Melanoma


Key Points

  • Talimogene laherparepvec was associated with a greater durable response rate vs granulocyte-macrophage colony-stimulating factor in advanced melanoma.
  • Efficacy was marked more in patients with stage IIIB/C or IV M1a disease and in treatment-naive patients.

In a phase III trial reported in the Journal of Clinical Oncology, Andtbacka et al found that talimogene laherparepvec (T-VEC) treatment improved the durable response rate vs granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with unresectable stage IIIB to IV melanoma. T-VEC is a herpes simplex virus (HSV) type 1–derived oncolytic immunotherapy designed to selectively replicate within tumors and produce GM-CSF to enhance the systemic antitumor immune response.  

Study Details

In this open-label trial, 436 patients with injectable melanoma from 64 centers in the United States, United Kingdom, Canada, and South Africa were randomly assigned 2:1 between May 2009 and July 2011 to intralesional T-VEC (n = 295) or subcutaneous GM-CSF (n = 141). The first dose of T-VEC was given at 106 pfu/mL (to seroconvert HSV-seronegative patients), followed by doses of 108 pfu/mL given 3 weeks after the first dose and then every 2 weeks. GM-CSF 125 µg/m2 was given once daily for 14 days in 28-day cycles. The primary endpoint was the rate of durable response rate, defined as an objective response lasting continuously for at least 6 months on independent assessment.


The durable response rate was 16.3% in the T-VEC group vs 2.1% in the GM-CSF group (odds ratio = 8.9, P < .001). The overall response rate was 26.4% vs 5.7% (P < .001), with complete response observed in 10.8% vs < 1%. The durable response benefit was marked more in patients with stage IIIB/C disease (33.0% vs 0%) or stage IV M1a disease (16.0% vs 2.3%) and in treatment-naive patients (23.9% vs 0%). Median overall survival was 23.3 months (95% confidence interval [CI] = 19.5–29.6 months) vs 18.9 months (95% CI = 16.0–23.7 months; hazard ratio = 0.79, P = .051).

Adverse Events

The most common adverse events of any grade in the T-VEC group were fatigue (50% vs 36% in the GM-CSF group), chills (49% vs 9%), pyrexia (43% vs 9%), and nausea (36% vs 20%). The only grade 3 or 4 adverse event occurring in > 2% of T-VEC patients was cellulitis (2.1%). Adverse events led to discontinuation of treatment in 4% vs 2% of patients. There were no fatal treatment-related adverse events.

The investigators concluded: “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 [durable response rate] (P < .001) and longer median [overall survival] (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.”

Howard L. Kaufman, MD, of Rutgers Cancer Institute of New Jersey, is the corresponding author of the Journal of Clinical Oncology article.

The study was supported by Amgen. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.