title: Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial.
abstract: Talimogene laherparepvec (T-VEC) is an oncolytic immunotherapy designed to induce tumor regression of injected lesions through direct lytic effects, and of uninjected lesions through induction of systemic antitumor immunity. In this study, we describe the patterns and time course of response to T-VEC from the phase III OPTiM trial of 436 patients with unresected stages IIIB-IV melanoma.
  
  
  
  Lesion-level response analyses were performed based on the type of lesion (injected or uninjected cutaneous, subcutaneous, or nodal lesions; or visceral lesions [uninjected]), and the best percentage change from baseline of the sum of products of the longest diameters was calculated. Patients randomized to T-VEC (n = 295) who experienced a durable response (continuous partial or complete response for ≥6 months) were evaluated for progression prior to response (PPR), defined as the appearance of a new lesion or >25 % increase in total baseline tumor area.
  
  
  
  T-VEC resulted in a decrease in size by ≥50 % in 64 % of injected lesions (N = 2116), 34 % of uninjected non-visceral lesions (N = 981), and 15 % of visceral lesions (N = 177). Complete resolution of lesions occurred in 47 % of injected lesions, 22 % of uninjected non-visceral lesions, and 9 % of visceral lesions. Of 48 patients with durable responses, 23 (48 %) experienced PPR, including 14 who developed new lesions only. No difference in overall survival was observed, and median duration of response was not reached in patients with PPR versus those without PPR.
  
  
  
  Responses in uninjected lesions provide validation of T-VEC-induced systemic immunotherapeutic effects against melanoma. PPR did not negatively impact the clinical effectiveness of T-VEC.
authors.affiliation: Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. Robert.Andtbacka@hci.utah.edu.
authors.forename: Robert H I
authors.initials: RH
authors.lastname: Andtbacka
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Merrick
authors.initials: M
authors.lastname: Ross
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.affiliation: University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Milhem
authors.affiliation: University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Frances
authors.initials: F
authors.lastname: Collichio
authors.affiliation: Emory University, Atlanta, GA, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Delman
authors.affiliation: Minnesota Oncology, Fridley, MN, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Amatruda
authors.affiliation: Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Zager
authors.affiliation: University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Cranmer
authors.affiliation: Saint Louis University Cancer Center, St Louis, MO, USA.
authors.forename: Eddy
authors.initials: E
authors.lastname: Hsueh
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Chen
authors.affiliation: Amgen Inc., Thousand Oaks, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Shilkrut
authors.affiliation: Rutgers Cancer Institute of New Jersey, Rutgers, NJ, USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000628:therapy; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000628:therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D015552:Injections, Intralesional; D007680:Kidney Neoplasms / Q000628:therapy; D008113:Liver Neoplasms / Q000628:therapy; D008175:Lung Neoplasms / Q000628:therapy; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D050130:Oncolytic Virotherapy; D010190:Pancreatic Neoplasms / Q000628:therapy; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*; D013160:Splenic Neoplasms / Q000628:therapy; D015996:Survival Rate; D013964:Thyroid Neoplasms / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor