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29 mei 2015: Bron: Journal of Clinical Oncology
Talimogene laherparepvec, geheten,
Studieresultaten:
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.
Het volledige studierapport: Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma is tegen betaling in te zien.
Hier het abstract van de studie:
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.
- © 2015 by American Society of Clinical Oncology
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,
- Wilson H. Miller Jr,
- Jonathan S. Zager,
- Yining Ye,
- Bin Yao,
- Ai Li,
- Susan Doleman,
- Ari VanderWalde,
- Jennifer Gansert and
- Robert Coffin
+ Author Affiliations
- Corresponding author: Howard L. Kaufman, MD, FACS, Rutgers Cancer Institute of New Jersey, 195 Little Albany St, New Brunswick, NJ 08901; e-mail: howard.kaufman@rutgers.edu.
-
Presented in part at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013, and 50th ASCO Annual Meeting, Chicago, IL, May 30-June 3, 2014.
-
R.H.I.A. and H.L.K. contributed equally to this work.
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.
Footnotes
-
Written on behalf of the OPTiM investigators.
-
Supported by Amgen, which also funded medical writing assistance.
-
Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.
-
Clinical trial information: NCT00769704.
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