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. Middleton & 9 others Wilson H. Miller, Jonathan S. Zager, Yining Ye, Bin Yao, Ai Li, Susan Doleman, Vanderwalde Ari, Jennifer Gansert, Robert S. Coffin

Research output: Contribution to journalArticle

710 Citations (Scopus)

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
Externally publishedYes

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Melanoma
Granulocyte-Macrophage Colony-Stimulating Factor
Immunotherapy
Survival
Chills
Phase III Clinical Trials
Cellulitis
Human Herpesvirus 1
Therapeutics
Fatigue
Fever
Odds Ratio
Injections
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Andtbacka, R. H. I., Kaufman, H. L., Collichio, F., Amatruda, T., Senzer, N., Chesney, J., ... 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

Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. / Andtbacka, Robert H.I.; Kaufman, Howard L.; Collichio, Frances; Amatruda, Thomas; Senzer, Neil; Chesney, Jason; Delman, Keith A.; Spitler, Lynn E.; Puzanov, Igor; Agarwala, Sanjiv S.; Milhem, Mohammed; Cranmer, Lee; Curti, Brendan; Lewis, Karl; Ross, Merrick; Guthrie, Troy; Linette, Gerald P.; Daniels, Gregory A.; Harrington, Kevin; Middleton, Mark R.; Miller, Wilson H.; Zager, Jonathan S.; Ye, Yining; Yao, Bin; Li, Ai; Doleman, Susan; Ari, Vanderwalde; Gansert, Jennifer; Coffin, Robert S.

In: Journal of Clinical Oncology, Vol. 33, No. 25, 01.09.2015, p. 2780-2788.

Research output: Contribution to journalArticle

Andtbacka, RHI, Kaufman, HL, Collichio, F, Amatruda, T, Senzer, N, Chesney, J, Delman, KA, Spitler, LE, Puzanov, I, Agarwala, SS, Milhem, M, Cranmer, L, Curti, B, Lewis, K, Ross, M, Guthrie, T, Linette, GP, Daniels, GA, Harrington, K, Middleton, MR, Miller, WH, Zager, JS, Ye, Y, Yao, B, Li, A, Doleman, S, Ari, V, Gansert, J & Coffin, RS 2015, 'Talimogene laherparepvec improves durable response rate in patients with advanced melanoma', Journal of Clinical Oncology, vol. 33, no. 25, pp. 2780-2788. https://doi.org/10.1200/JCO.2014.58.3377
Andtbacka RHI, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. Journal of Clinical Oncology. 2015 Sep 1;33(25):2780-2788. https://doi.org/10.1200/JCO.2014.58.3377
Andtbacka, Robert H.I. ; Kaufman, Howard L. ; Collichio, Frances ; Amatruda, Thomas ; Senzer, Neil ; Chesney, Jason ; Delman, Keith A. ; Spitler, Lynn E. ; Puzanov, Igor ; Agarwala, Sanjiv S. ; Milhem, Mohammed ; Cranmer, Lee ; Curti, Brendan ; Lewis, Karl ; Ross, Merrick ; Guthrie, Troy ; Linette, Gerald P. ; Daniels, Gregory A. ; Harrington, Kevin ; Middleton, Mark R. ; Miller, Wilson H. ; Zager, Jonathan S. ; Ye, Yining ; Yao, Bin ; Li, Ai ; Doleman, Susan ; Ari, Vanderwalde ; Gansert, Jennifer ; Coffin, Robert S. / Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 25. pp. 2780-2788.
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title = "Talimogene laherparepvec improves durable response rate in patients with advanced melanoma",
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.",
author = "Andtbacka, {Robert H.I.} and Kaufman, {Howard L.} and Frances Collichio and Thomas Amatruda and Neil Senzer and Jason Chesney and Delman, {Keith A.} and Spitler, {Lynn E.} and Igor Puzanov and Agarwala, {Sanjiv S.} and Mohammed Milhem and Lee Cranmer and Brendan Curti and Karl Lewis and Merrick Ross and Troy Guthrie and Linette, {Gerald P.} and Daniels, {Gregory A.} and Kevin Harrington and Middleton, {Mark R.} and Miller, {Wilson H.} and Zager, {Jonathan S.} and Yining Ye and Bin Yao and Ai Li and Susan Doleman and Vanderwalde Ari and Jennifer Gansert and Coffin, {Robert S.}",
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TY - JOUR

T1 - Talimogene laherparepvec improves durable response rate in patients with advanced melanoma

AU - Andtbacka, Robert H.I.

AU - Kaufman, Howard L.

AU - Collichio, Frances

AU - Amatruda, Thomas

AU - Senzer, Neil

AU - Chesney, Jason

AU - Delman, Keith A.

AU - Spitler, Lynn E.

AU - Puzanov, Igor

AU - Agarwala, Sanjiv S.

AU - Milhem, Mohammed

AU - Cranmer, Lee

AU - Curti, Brendan

AU - Lewis, Karl

AU - Ross, Merrick

AU - Guthrie, Troy

AU - Linette, Gerald P.

AU - Daniels, Gregory A.

AU - Harrington, Kevin

AU - Middleton, Mark R.

AU - Miller, Wilson H.

AU - Zager, Jonathan S.

AU - Ye, Yining

AU - Yao, Bin

AU - Li, Ai

AU - Doleman, Susan

AU - Ari, Vanderwalde

AU - Gansert, Jennifer

AU - Coffin, Robert S.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

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