Patterns of durable response with intralesional talimogene laherparepvec (T-VEC): Results from a phase III trial in patients with stage IIIb-IV melanoma.

Melanoma/Skin Cancers
Session Type and Session Title: 
Poster Highlights Session, Melanoma/Skin Cancers
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 9026)
Merrick I. Ross, Robert Hans Ingemar Andtbacka, Igor Puzanov, Mohammed M. Milhem, Frances A. Collichio, Keith A. Delman, R Dirk Noyes, Jonathan S. Zager, Lee D. Cranmer, Lynn E. Spitler, Eddy C. Hsueh, David W. Ollila, Thomas Amatruda, Lisa Chen, Jennifer L. Gansert, Howard L Kaufman; The University of Texas MD Anderson Cancer Center, Houston, TX; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Vanderbilt-Ingram Cancer Center, Vanderbilt University, School of Medicine, Nashville, TN; University of Iowa Hospitals and Clinics, Iowa City, IA; The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC; Department of Surgery, Emory University, Atlanta, GA; University of Utah, School of Medicine, Salt Lake City, UT; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; The University of Arizona Cancer Center, Tucson, AZ; Northern California Melanoma Center, San Francisco, CA; St. Louis University, St. Louis, MO; The University of North Carolina at Chapel Hill, Chapel Hill, NC; Minnesota Oncology, Fridley, MN; Amgen Inc., Thousand Oaks, CA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ

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Abstract Disclosures


Background: T-VEC is an intralesional oncolytic immunotherapy comprising a modified HSV-type 1. In the randomized OPTiM phase 3 trial, T-VEC significantly improved DR rate (DRR, continuous partial or complete response for ≥6 mo) by 16% vs 2% and overall RR by 26% vs 6% vs subcutaneous (SC) GM-CSF in patients (pts) with advanced melanoma. We hypothesized that some pts progressed on treatment (tx) prior to DR and sought to determine how such events impacted the durability of response. Here we describe response patterns in T-VEC-treated pts with a DR. Methods: 436 pts with Stage IIIB-IV melanoma were randomized 2:1 to receive intralesional T-VEC or SC GM-CSF until clinically significant PD, intolerability, or lack of injectable lesions. Tx was to continue for at least 6 mo during which tx discontinuation for PD was not required. PD prior to response (PPR) was defined as the appearance of a new lesion or >25% increase in baseline tumor burden. Injection of new lesions was allowed. Responders were grouped as 1) PPR or 2) no PPR. PPR was grouped by a) existing lesions (± new lesions) or b) new lesions only. Pts without PPR were grouped by DR onset at ≤6 mo or >6 mo. Results: Of 48 T-VEC pts with a DR, 23 (48%) had PPR: 9 (39%) pts had PD in existing lesions (± new lesions) and 14 (61%) had new lesions only. For 25 pts with no PPR, 21 (84%) had a DR beginning within the first 6 mo. 40 (83%) of the DRs remain in remission with a median follow up of over 18.4 mo. Conclusions: Similar to other immunotherapies, PPR was common in T-VEC-treated pts. Most PPRs included the development of new lesions, thus T-VEC tx should continue through PD. The quality of DR does not seem to be negatively affected by PPR or the timing of achieving DR. These data reinforce the evolving new paradigm of response criteria when treating pts with melanoma with immunotherapeutic agents. Clinical trial information: NCT00769704.

DR by PPR Status.
Without PPR
With PPR
Median (Min, Max) time to DR (mo)a 3.1 (1.2, 9.5) 5.8 (1.3, 10.6)
Median (Min, Max) duration of DR (mo) NE (6.2+, NE) NE (6.3, NE)
DR maintained at end of follow-up, n (%)b 22 (88%) 18 (78%)

aP=0.004, Wilcoxon rank sum test; bP=0.27, log rank test; NE, Not evaluable, median not reached; +censored.