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 - Van Der Walde, Ari
AU - Gansert, Jennifer
AU - Coffin, Robert S.
N1 - Publisher Copyright:
© 2015 by American Society of Clinical Oncology.
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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U2 - 10.1200/JCO.2014.58.3377
DO - 10.1200/JCO.2014.58.3377
M3 - Article
C2 - 26014293
AN - SCOPUS:84933586864
SN - 0732-183X
VL - 33
SP - 2780
EP - 2788
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 25
ER -