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J Clin Oncol. 2015 Sep 1;33(25):2780-8. doi: 10.1200/JCO.2014.58.3377. Epub 2015 May 26.

Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma.

Author information

  • 1Robert H.I. Andtbacka, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Howard L. Kaufman, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Frances Collichio, University of North Carolina Medical Center, Chapel Hill, NC; Thomas Amatruda, Minnesota Oncology, Fridley, MN; Neil Senzer, Mary Crowley Cancer Research Center, Dallas; Merrick Ross, University of Texas MD Anderson Cancer Center, Houston, TX; Jason Chesney, University of Louisville, Louisville, KY; Keith A. Delman, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA; Lynn E. Spitler, Northern California Melanoma Center, San Francisco; Gregory A. Daniels, University of California San Diego Medical Center, Moores Cancer Center, La Jolla; Yining Ye, Bin Yao, Ai Li, Ari Vander Walde, and Jennifer Gansert, Amgen, Thousand Oaks, CA; Igor Puzanov, Vanderbilt University, Nashville, TN; Sanjiv S. Agarwala, St Luke's University Hospital and Health Network, Bethlehem, and Temple University School of Medicine, Philadelphia, PA; Mohammed Milhem, University of Iowa Hospitals and Clinics, Iowa City, IA; Lee Cranmer, University of Arizona, Tucson, AZ; Brendan Curti, Earle A. Chiles Research Institute, Portland, OR; Karl Lewis, University of Colorado Cancer Center, Aurora, CO; Troy Guthrie, Baptist Cancer Institute, Jacksonville; Jonathan S. Zager, Moffitt Cancer Center, Tampa, FL; Gerald P. Linette, Washington University School of Medicine, St Louis, MO; Kevin Harrington, Institute of Cancer Research, Royal Marsden Hospital, London; Mark R. Middleton, National Institute for Health Research Biomedical Research Centre, Oxford, United Kingdom; Wilson H. Miller Jr, McGill University, Montreal, Quebec, Canada; and Susan Doleman and Robert S. Coffin, Amgen, Woburn, MA.
  • 2Robert H.I. Andtbacka, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Howard L. Kaufman, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Frances Collichio, University of North Carolina Medical Center, Chapel Hill, NC; Thomas Amatruda, Minnesota Oncology, Fridley, MN; Neil Senzer, Mary Crowley Cancer Research Center, Dallas; Merrick Ross, University of Texas MD Anderson Cancer Center, Houston, TX; Jason Chesney, University of Louisville, Louisville, KY; Keith A. Delman, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA; Lynn E. Spitler, Northern California Melanoma Center, San Francisco; Gregory A. Daniels, University of California San Diego Medical Center, Moores Cancer Center, La Jolla; Yining Ye, Bin Yao, Ai Li, Ari Vander Walde, and Jennifer Gansert, Amgen, Thousand Oaks, CA; Igor Puzanov, Vanderbilt University, Nashville, TN; Sanjiv S. Agarwala, St Luke's University Hospital and Health Network, Bethlehem, and Temple University School of Medicine, Philadelphia, PA; Mohammed Milhem, University of Iowa Hospitals and Clinics, Iowa City, IA; Lee Cranmer, University of Arizona, Tucson, AZ; Brendan Curti, Earle A. Chiles Research Institute, Portland, OR; Karl Lewis, University of Colorado Cancer Center, Aurora, CO; Troy Guthrie, Baptist Cancer Institute, Jacksonville; Jonathan S. Zager, Moffitt Cancer Center, Tampa, FL; Gerald P. Linette, Washington University School of Medicine, St Louis, MO; Kevin Harrington, Institute of Cancer Research, Royal Marsden Hospital, London; Mark R. Middleton, National Institute for Health Research Biomedical Research Centre, Oxford, United Kingdom; Wilson H. Miller Jr, McGill University, Montreal, Quebec, Canada; and Susan Doleman and Robert S. Coffin, Amgen, Woburn, MA. howard.kaufman@rutgers.edu.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00769704.

PMID:
26014293
DOI:
10.1200/JCO.2014.58.3377
[PubMed - indexed for MEDLINE]
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