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 D Cranmer, Eddy Hsueh, Lisa Chen, Mark Shilkrut, Howard L. Kaufman

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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.

Original languageEnglish (US)
Pages (from-to)4169-4177
Number of pages9
JournalAnnals of Surgical Oncology
Volume23
Issue number13
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

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Phase III Clinical Trials
Melanoma
Immunotherapy
Immunity
Neoplasms
Skin
Survival

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial. / Andtbacka, Robert H I; Ross, Merrick; Puzanov, Igor; Milhem, Mohammed; Collichio, Frances; Delman, Keith A.; Amatruda, Thomas; Zager, Jonathan S.; Cranmer, Lee D; Hsueh, Eddy; Chen, Lisa; Shilkrut, Mark; Kaufman, Howard L.

In: Annals of Surgical Oncology, Vol. 23, No. 13, 01.12.2016, p. 4169-4177.

Research output: Contribution to journalArticle

Andtbacka, RHI, Ross, M, Puzanov, I, Milhem, M, Collichio, F, Delman, KA, Amatruda, T, Zager, JS, Cranmer, LD, Hsueh, E, Chen, L, Shilkrut, M & Kaufman, HL 2016, 'Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial', Annals of Surgical Oncology, vol. 23, no. 13, pp. 4169-4177. https://doi.org/10.1245/s10434-016-5286-0
Andtbacka, Robert H I ; Ross, Merrick ; Puzanov, Igor ; Milhem, Mohammed ; Collichio, Frances ; Delman, Keith A. ; Amatruda, Thomas ; Zager, Jonathan S. ; Cranmer, Lee D ; Hsueh, Eddy ; Chen, Lisa ; Shilkrut, Mark ; Kaufman, Howard L. / Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial. In: Annals of Surgical Oncology. 2016 ; Vol. 23, No. 13. pp. 4169-4177.
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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.",
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T1 - Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial

AU - Andtbacka, Robert H I

AU - Ross, Merrick

AU - Puzanov, Igor

AU - Milhem, Mohammed

AU - Collichio, Frances

AU - Delman, Keith A.

AU - Amatruda, Thomas

AU - Zager, Jonathan S.

AU - Cranmer, Lee D

AU - Hsueh, Eddy

AU - Chen, Lisa

AU - Shilkrut, Mark

AU - Kaufman, Howard L.

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N2 - 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.

AB - 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.

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