133898-144

Primary overall survival (OS) from OPTiM, a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

Subcategory: 
Category: 
Melanoma/Skin Cancers
Session Type and Session Title: 
Oral Abstract Session, Melanoma/Skin Cancers
Abstract Number: 
9008a
Citation: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 9008a)
Author(s): 
Howard L Kaufman, Robert Hans Ingemar Andtbacka, Frances A. Collichio, Thomas Amatruda, Neil N. Senzer, Jason Chesney, Keith A. Delman, Lynn E. Spitler, Igor Puzanov, Yining Ye, Ai Li, Jennifer L. Gansert, Robert Coffin, Merrick I. Ross; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC; Minnesota Oncology, Fridley, MN; Mary Crowley Cancer Research Centers, Dallas, TX; University of Louisville, Louisville, KY; Department of Surgery, Emory University, Atlanta, GA; Northern California Melanoma Center, San Francisco, CA; Vanderbilt-Ingram Cancer Center, Vanderbilt University, School of Medicine, Nashville, TN; Department of Biostatistics and Epidemiology, Amgen Inc., South San Francisco, CA; Department of Biostatistics and Epidemiology, Amgen Inc., Thousand Oaks, CA; Amgen Inc., Thousand Oaks, CA; Amgen Woburn, Woburn, MA; The University of Texas MD Anderson Cancer Center, Houston, TX

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

Background: T-VEC is an oncolytic immunotherapy derived from herpes simplex virus type-1 designed to selectively replicate in tumors and produce GM-CSF to enhance systemic antitumor immune responses. OPTiM is a randomized, phase 3 trial of T-VEC or GM-CSF in patients (pts) with unresected melanoma with regional or distant metastases (NCT00769704). OPTiM met the primary endpoint of a statistically significant improvement in durable response rate (DRR) with T-VEC vs GM-CSF (Andtbacka et al. ASCO 2013). The primary analysis of OS is reported here. Methods: Key entry criteria were age ≥ 18 yrs, ECOG ≤1, unresectable melanoma stage IIIB/C or IV, injectable cutaneous, SC, or nodal lesions, LDH ≤1.5X ULN, ≤ 3 visceral lesions (excluding lung), none > 3 cm. Pts were randomized 2:1 to intralesional T-VEC (initially ≤ 4 mL x106 pfu/mL then after 3 wks, ≤ 4 mL x108 pfu/mL Q2W) or SC GM-CSF (125 µg/m2qd x 14 days q28d). The primary endpoint was DRR: partial or complete response continuously for ≥ 6 mos starting within 12 mos. Responses were per modified WHO by blinded central review. The primary analysis of OS (290 planned events) had 90% power to detect a HR of 0.67 with two sided α=0.05. Results: 436 pts are in the ITT set: 295 (68%) T-VEC, 141 (32%) GM-CSF. 57% were men; median age was 63 yrs. An increase of 4.4 mos in OS with T-VEC vs GM-CSF was observed (p =0.051): HR 0.787 (95% CI: 0.62, 1.00); median (95% CI) OS was 23.3 (19.5, 29.6) mos with T-VEC vs 18.9 (16.0, 23.7) mos with GM-CSF. Objective response rate with T-VEC was 26% (95% CI: 21%, 32%) with 11% CR, and with GM-CSF was 6% (95% CI: 2%, 10%) with 1% CR. DRR for T-VEC was 16% (95% CI: 12%, 21%) and 2% for GM-CSF (95% CI: 0%, 5%), p<0.0001. Most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. No ≥ grade 3 AE occurred in ≥ 3% of pts in either arm. Conclusions: In pts with unresectable Stage IIIB-IV melanoma, T-VEC demonstrated a significant improvement in the DRR vs GM-CSF with a tolerable safety profile. An improvement in OS approaching statistical significance was seen in the ITT population. Clinical trial information: NCT00769704.