Dummer et al. reported the safety, efficacy, and biomarker analysis results from an open label, phase 2 trial of neoadjuvant talimogene laherparepvec (T-VEC) followed by surgery (arm 1, n= 76) or only surgery (arm 2, n=74) in patients with advanced resectable melanoma. The two-year RFS was 29.9% in arm 1 and 16.5% in arm 2, and the two-year OS estimate was 88.9% for arm 1 and 77.4% for arm 2. Neoadjuvant T-VEC was well tolerated, consistent with its known safety profile, and increased intralesional CD8+ T cell density, which correlated with improved therapy response. The RFS and OS results at 3 years were consistent with those at 2 years.
Contributed by Shishir Pant
ABSTRACT: Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-based intralesional oncolytic immunotherapy approved for the treatment of unresectable melanoma. The present, ongoing study aimed to estimate the treatment effect of neoadjuvant T-VEC on recurrence-free survival (RFS) of patients with advanced resectable melanoma. An open-label, phase 2 trial (NCT02211131) was conducted in 150 patients with resectable stage IIIB-IVM1a melanoma who were randomized to receive T-VEC followed by surgery (arm 1, n = 76) or surgery alone (arm 2, n = 74). The primary endpoint was a 2-year RFS in the intention-to-treat population. Secondary and exploratory endpoints included overall survival (OS), pathological complete response (pCR), safety and biomarker analyses. The 2-year RFS was 29.5% in arm 1 and 16.5% in arm 2 (overall hazard ratio (HR) = 0.75, 80% confidence interval (CI) = 0.58-0.96). The 2-year OS was 88.9% for arm 1 and 77.4% for arm 2 (overall HR = 0.49, 80% CI = 0.30-0.79). The RFS and OS differences between arms persisted at 3 years. In arm 1, 17.1% achieved a pCR. Increased CD8+ density correlated with clinical outcomes in an exploratory analysis. Arm 1 adverse events were consistent with previous reports for T-VEC. The present study met its primary endpoint and estimated a 25% reduction in the risk of disease recurrence for neoadjuvant T-VEC plus surgery versus upfront surgery for patients with resectable stage IIIB-IVM1a melanoma.
Author Info: (1) University Hospital of Zurich, Zurich, Switzerland. Reinhard.Dummer@usz.ch. (2) Olivia Newton-John Cancer Centre, Austin Health, Heidelberg, Victoria, Australia. (3) University
Author Info: (1) University Hospital of Zurich, Zurich, Switzerland. Reinhard.Dummer@usz.ch. (2) Olivia Newton-John Cancer Centre, Austin Health, Heidelberg, Victoria, Australia. (3) University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA. (4) Thomas Jefferson University Hospitals, Philadelphia, PA, USA. Cancer Institute of New Jersey, New Brunswick, NJ, USA. (5) University of Alabama School of Medicine, Birmingham, AL, USA. (6) N.N. Blokhin Russian Cancer Research Center, Moscow, Russia. (7) Amgen Inc., Thousand Oaks, CA, USA. (8) Amgen Inc., South San Francisco, CA, USA. (9) Amgen Inc., Uxbridge, UK. (10) Amgen Inc., South San Francisco, CA, USA. (11) Amgen Inc., Thousand Oaks, CA, USA. (12) Amgen Inc., Thousand Oaks, CA, USA. (13) John Wayne Cancer Institute, Santa Monica, CA, USA. The Angeles Clinic and Research Institute, Los Angeles, CA, USA. (14) University of Texas MD Anderson Cancer Center, Houston, TX, USA.
