Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial

Kevin J Harrington,¹ Robert HI Andtbacka,² Frances Collichio,³ Gerald Downey,⁴ Lisa Chen,⁵ Zsolt Szabo,⁶ Howard L Kaufman<sup>7

1</sup>The Institute of Cancer Research/The Royal Marsden Hospital NIHR Biomedical Research Centre, London, UK; ²Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; ³Division of Hematology and Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; ⁴Amgen Ltd, Cambridge, UK; ⁵Amgen Inc, Thousand Oaks, CA, USA; ⁶Amgen GmbH, Zug, Switzerland; ⁷Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

Objectives: Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage colony-stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB–IVM1c melanoma. The median overall survival (OS) was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB–IVM1a). Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB–IVM1a disease.
Patients and methods: The patients were randomized (2:1 ratio) to intralesional talimogene laherparepvec or subcutaneous GM-CSF and were evaluated for DRR, overall response rate (ORR), OS, safety, benefit–risk and numbers needed to treat. Descriptive statistics were used for subgroup comparisons.
Results: Among 249 evaluated patients with stage IIIB–IVM1a melanoma, DRR was higher with talimogene laherparepvec compared with GM-CSF (25.2% versus 1.2%; P<0.0001). ORR was also higher in the talimogene laherparepvec arm (40.5% versus 2.3%; P<0.0001), and 27 patients in the talimogene laherparepvec arm had a complete response, compared with none in GM-CSF-treated patients. The incidence rates of exposure-adjusted adverse events (AE) and serious AEs were similar with both treatments.
Conclusion: The subgroup of patients with stage IIIB, IIIC and IVM1a melanoma (57.1% of the OPTiM intent-to-treat population) derived greater benefit in DRR and ORR from talimogene laherparepvec compared with GM-CSF. Talimogene laherparepvec was well tolerated.

Keywords: benefit–risk, clinical trial, durable response rate, immunotherapy, oncolytic virus, talimogene laherparepvec