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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Institute of Cancer Research/The Royal Marsden Hospital NIHR Biomedical Research Centre, London, UK.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Harrington
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
authors.forename: Robert Hi
authors.initials: RH
authors.lastname: Andtbacka
authors.affiliation: Division of Hematology and Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Frances
authors.initials: F
authors.lastname: Collichio
authors.affiliation: Amgen Ltd, Cambridge, UK.
authors.forename: Gerald
authors.initials: G
authors.lastname: Downey
authors.affiliation: Amgen Inc, Thousand Oaks, CA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Chen
authors.affiliation: Amgen GmbH, Zug, Switzerland.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szabo
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
keywords: benefit–risk; clinical trial; durable response rate; immunotherapy; oncolytic virus; talimogene laherparepvec