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

Robert H I Andtbacka; Merrick Ross; Igor Puzanov; Mohammed Milhem; Frances Collichio; Keith A Delman; Thomas Amatruda; Jonathan S Zager; Lee Cranmer; Eddy Hsueh; Lisa Chen; Mark Shilkrut; Howard L Kaufman

doi:10.1245/s10434-016-5286-0

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

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

Robert H I Andtbacka, Merrick Ross, Igor Puzanov, Mohammed Milhem, Frances Collichio, Keith A Delman, Thomas Amatruda, Jonathan S Zager, Lee Cranmer, Eddy Hsueh, …

Annals of surgical oncology, Vol.23(13), pp.4169-4177

12/2016

DOI: 10.1245/s10434-016-5286-0

PMCID: PMC5090012

PMID: 27342831

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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.

Skin Neoplasms - pathology

Splenic Neoplasms - therapy

Skin Neoplasms - therapy

Humans

Male

Survival Rate

Treatment Outcome

Liver Neoplasms - therapy

Lung Neoplasms - therapy

Lymphatic Metastasis

Gastrointestinal Neoplasms - therapy

Tumor Burden

Granulocyte-Macrophage Colony-Stimulating Factor - therapeutic use

Melanoma - secondary

Oncolytic Virotherapy

Thyroid Neoplasms - therapy

Time Factors

Injections, Intralesional

Female

Herpesvirus 1, Human - immunology

Melanoma - therapy

Kidney Neoplasms - therapy

Adrenal Gland Neoplasms - therapy

Pancreatic Neoplasms - therapy

Details

Title: Subtitle: Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial
Creators: Robert H I Andtbacka - Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. Robert.Andtbacka@hci.utah.edu
Merrick Ross - University of Texas MD Anderson Cancer Center, Houston, TX, USA
Igor Puzanov - Vanderbilt University Medical Center, Nashville, TN, USA
Mohammed Milhem - University of Iowa Hospitals and Clinics, Iowa City, IA, USA
Frances Collichio - University of North Carolina, Chapel Hill, NC, USA
Keith A Delman - Emory University, Atlanta, GA, USA
Thomas Amatruda - Minnesota Oncology, Fridley, MN, USA
Jonathan S Zager - Moffitt Cancer Center, Tampa, FL, USA
Lee Cranmer - University of Washington School of Medicine, Seattle, WA, USA
Eddy Hsueh - Saint Louis University Cancer Center, St Louis, MO, USA
Lisa Chen - Amgen Inc., Thousand Oaks, CA, USA
Mark Shilkrut - Amgen Inc., Thousand Oaks, CA, USA
Howard L Kaufman - Rutgers Cancer Institute of New Jersey, Rutgers, NJ, USA
Resource Type: Journal article
Publication Details: Annals of surgical oncology, Vol.23(13), pp.4169-4177
DOI: 10.1245/s10434-016-5286-0
PMID: 27342831
PMCID: PMC5090012
NLM abbreviation: Ann Surg Oncol
ISSN: 1068-9265
eISSN: 1534-4681
Grant note: P30 CA086862 / NCI NIH HHS
Language: English
Date published: 12/2016
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094215102771

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