Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma
| Autor: | Neil Senzer, Igor Puzanov, Bin Yao, Gerald P. Linette, Lynn E. Spitler, Sanjiv S. Agarwala, Susan Doleman, Troy H. Guthrie, Jason Chesney, Ari M. Vanderwalde, Robert Coffin, Keith A. Delman, Lee D. Cranmer, Kevin J. Harrington, Karl D. Lewis, Gregory A. Daniels, Jennifer Gansert, Jonathan S. Zager, Merrick I. Ross, Brendan D. Curti, Ai Li, Mark R. Middleton, Howard L. Kaufman, Wilson H. Miller, Mohammed M. Milhem, Thomas Amatruda, Yining Ye, Frances A. Collichio, Robert H.I. Andtbacka |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Skin Neoplasms Time Factors Fever Antineoplastic Agents Herpesvirus 1 Human Injections Intralesional Gastroenterology Oncolytic herpes virus Adjuvants Immunologic Internal medicine Clinical endpoint Odds Ratio Medicine Humans Adverse effect Melanoma Survival analysis Fatigue Aged Neoplasm Staging Aged 80 and over Oncolytic Virotherapy business.industry Hazard ratio Granulocyte-Macrophage Colony-Stimulating Factor Odds ratio Middle Aged Survival Analysis Chills United States Surgery Oncolytic Viruses Treatment Outcome Oncology Female Immunotherapy medicine.symptom business Talimogene laherparepvec |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 33(25) |
| ISSN: | 1527-7755 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|