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, Mohammed Milhem, Lee Cranmer, Brendan Curti, Karl Lewis, Merrick Ross, Troy Guthrie, Gerald P. Linette, Gregory A. Daniels, Kevin Harrington, Mark R. MiddletonWilson H. Miller, Jonathan S. Zager, Yining Ye, Bin Yao, Ai Li, Susan Doleman, Ari Van Der Walde, Jennifer Gansert, Robert S. Coffin

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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). Overal 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.

Original languageEnglish (US)
Pages (from-to)2780-2788
Number of pages9
JournalJournal of Clinical Oncology
Volume33
Issue number25
DOIs
StatePublished - Sep 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Andtbacka, R. H. I., Kaufman, H. L., Collichio, F., Amatruda, T., Senzer, N., Chesney, J., Delman, K. A., Spitler, L. E., Puzanov, I., Agarwala, S. S., Milhem, M., Cranmer, L., Curti, B., Lewis, K., Ross, M., Guthrie, T., Linette, G. P., Daniels, G. A., Harrington, K., ... Coffin, R. S. (2015). Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. Journal of Clinical Oncology, 33(25), 2780-2788. https://doi.org/10.1200/JCO.2014.58.3377