Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial

• Type of Material: Article
• Authors: Robert H.I. Andtbacka, University of Utah; Merrick Ross, MD Anderson Cancer Center; Igor Puzanov, Vanderbilt University; Mohammed Milhem, University of Iowa; Frances Collichio, University of North Carolina; Keith Delman, Emory University; Thomas Amatruda, Minnesota Oncology; Jonathan S. Zager, Moffitt Cancer Center; Lee Cranmer, University of Washington; Eddy Hsueh, Saint Louis University; Lisa Chen, Amgen Inc.; Mark Shilkrut, Amgen Inc.; Howard L. Kaufman, Rutgers Cancer Institute of New Jersey
• Language: English
• Date: 2016-12-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Final Published Version
• Copyright Statement: © 2016, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1245/s10434-016-5286-0
• Title of Journal or Parent Work: Annals of Surgical Oncology
• ISSN: 1068-9265
• Volume: 23
• Issue: 13
• Start Page: 4169
• End Page: 4177
• Keywords: CRITERIA; Life Sciences & Biomedicine; HERPES-SIMPLEX-VIRUS; Science & Technology; SOLID TUMORS; IMMUNE-RELATED RESPONSE; Surgery; Oncology
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.