Cargando…

Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial

OBJECTIVES: Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage...

Descripción completa

Detalles Bibliográficos
Autores principales: Harrington, Kevin J, Andtbacka, Robert HI, Collichio, Frances, Downey, Gerald, Chen, Lisa, Szabo, Zsolt, Kaufman, Howard L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119624/
https://www.ncbi.nlm.nih.gov/pubmed/27895500
http://dx.doi.org/10.2147/OTT.S115245
_version_ 1782469103500394496
author Harrington, Kevin J
Andtbacka, Robert HI
Collichio, Frances
Downey, Gerald
Chen, Lisa
Szabo, Zsolt
Kaufman, Howard L
author_facet Harrington, Kevin J
Andtbacka, Robert HI
Collichio, Frances
Downey, Gerald
Chen, Lisa
Szabo, Zsolt
Kaufman, Howard L
author_sort Harrington, Kevin J
collection PubMed
description OBJECTIVES: Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage colony-stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB–IVM1c melanoma. The median overall survival (OS) was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB–IVM1a). Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB–IVM1a disease. PATIENTS AND METHODS: The patients were randomized (2:1 ratio) to intralesional talimogene laherparepvec or subcutaneous GM-CSF and were evaluated for DRR, overall response rate (ORR), OS, safety, benefit–risk and numbers needed to treat. Descriptive statistics were used for subgroup comparisons. RESULTS: Among 249 evaluated patients with stage IIIB–IVM1a melanoma, DRR was higher with talimogene laherparepvec compared with GM-CSF (25.2% versus 1.2%; P<0.0001). ORR was also higher in the talimogene laherparepvec arm (40.5% versus 2.3%; P<0.0001), and 27 patients in the talimogene laherparepvec arm had a complete response, compared with none in GM-CSF-treated patients. The incidence rates of exposure-adjusted adverse events (AE) and serious AEs were similar with both treatments. CONCLUSION: The subgroup of patients with stage IIIB, IIIC and IVM1a melanoma (57.1% of the OPTiM intent-to-treat population) derived greater benefit in DRR and ORR from talimogene laherparepvec compared with GM-CSF. Talimogene laherparepvec was well tolerated.
format Online
Article
Text
id pubmed-5119624
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Dove Medical Press
record_format MEDLINE/PubMed
spelling pubmed-51196242016-11-28 Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial Harrington, Kevin J Andtbacka, Robert HI Collichio, Frances Downey, Gerald Chen, Lisa Szabo, Zsolt Kaufman, Howard L Onco Targets Ther Original Research OBJECTIVES: Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage colony-stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB–IVM1c melanoma. The median overall survival (OS) was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB–IVM1a). Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB–IVM1a disease. PATIENTS AND METHODS: The patients were randomized (2:1 ratio) to intralesional talimogene laherparepvec or subcutaneous GM-CSF and were evaluated for DRR, overall response rate (ORR), OS, safety, benefit–risk and numbers needed to treat. Descriptive statistics were used for subgroup comparisons. RESULTS: Among 249 evaluated patients with stage IIIB–IVM1a melanoma, DRR was higher with talimogene laherparepvec compared with GM-CSF (25.2% versus 1.2%; P<0.0001). ORR was also higher in the talimogene laherparepvec arm (40.5% versus 2.3%; P<0.0001), and 27 patients in the talimogene laherparepvec arm had a complete response, compared with none in GM-CSF-treated patients. The incidence rates of exposure-adjusted adverse events (AE) and serious AEs were similar with both treatments. CONCLUSION: The subgroup of patients with stage IIIB, IIIC and IVM1a melanoma (57.1% of the OPTiM intent-to-treat population) derived greater benefit in DRR and ORR from talimogene laherparepvec compared with GM-CSF. Talimogene laherparepvec was well tolerated. Dove Medical Press 2016-11-16 /pmc/articles/PMC5119624/ /pubmed/27895500 http://dx.doi.org/10.2147/OTT.S115245 Text en © 2016 Harrington et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Harrington, Kevin J
Andtbacka, Robert HI
Collichio, Frances
Downey, Gerald
Chen, Lisa
Szabo, Zsolt
Kaufman, Howard L
Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial
title Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial
title_full Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial
title_fullStr Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial
title_full_unstemmed Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial
title_short Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial
title_sort efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage iiib/c and ivm1a melanoma: subanalysis of the phase iii optim trial
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119624/
https://www.ncbi.nlm.nih.gov/pubmed/27895500
http://dx.doi.org/10.2147/OTT.S115245
work_keys_str_mv AT harringtonkevinj efficacyandsafetyoftalimogenelaherparepvecversusgranulocytemacrophagecolonystimulatingfactorinpatientswithstageiiibcandivm1amelanomasubanalysisofthephaseiiioptimtrial
AT andtbackaroberthi efficacyandsafetyoftalimogenelaherparepvecversusgranulocytemacrophagecolonystimulatingfactorinpatientswithstageiiibcandivm1amelanomasubanalysisofthephaseiiioptimtrial
AT collichiofrances efficacyandsafetyoftalimogenelaherparepvecversusgranulocytemacrophagecolonystimulatingfactorinpatientswithstageiiibcandivm1amelanomasubanalysisofthephaseiiioptimtrial
AT downeygerald efficacyandsafetyoftalimogenelaherparepvecversusgranulocytemacrophagecolonystimulatingfactorinpatientswithstageiiibcandivm1amelanomasubanalysisofthephaseiiioptimtrial
AT chenlisa efficacyandsafetyoftalimogenelaherparepvecversusgranulocytemacrophagecolonystimulatingfactorinpatientswithstageiiibcandivm1amelanomasubanalysisofthephaseiiioptimtrial
AT szabozsolt efficacyandsafetyoftalimogenelaherparepvecversusgranulocytemacrophagecolonystimulatingfactorinpatientswithstageiiibcandivm1amelanomasubanalysisofthephaseiiioptimtrial
AT kaufmanhowardl efficacyandsafetyoftalimogenelaherparepvecversusgranulocytemacrophagecolonystimulatingfactorinpatientswithstageiiibcandivm1amelanomasubanalysisofthephaseiiioptimtrial