Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

J Clin Oncol. 2015 Sep 1;33(25):2780-8. doi: 10.1200/JCO.2014.58.3377. Epub 2015 May 26.

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.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Granulocyte-Macrophage Colony-Stimulating Factor

Associated data

  • ClinicalTrials.gov/NCT00769704