Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus, type 1 (HSV-1), which can be administered intralesionally in patients with stage IIIB/C-IVM1a unresectable melanoma (EMA label). The phase 3 OPTiM registration study showed an overall response rate (ORR) of 26%.
Since approval of T-VEC in the Netherlands in December 2016, 35 eligible patients started treatment with T-VEC monotherapy at the Netherlands Cancer Institute. We included 23 patients with a follow up time ≥6 months. Analysis of overall response rate (ORR), adverse events (AE), prior treatment for melanoma and baseline characteristics, documented in a prospectively maintained database. Besides clinical evaluation, in this study we used PET-CT and histological biopsies for response evaluation.
The median follow-up was 11.3 months. Of 23 patients, 12 (52.2%) had a complete response (CR) as their best response, all except for one ongoing after stopping treatment. As their best response, 7 (30.4%) patients had a partial response (PR), 2 (8.7%) patients had a mixed response and 2 (8.7%) patients showed progressive disease (PD). ORR for the analyzed cohort was 82.6%. Disease Control Rate (DCR) was 91.3%. At baseline, the mean number of lesions was between 5 and 50 lesions. Grade 1-2 AE’s occurred in all patients. Mostly, these consisted of fatigue, influenza-like symptoms and injection site pain. 1 patient had to pause treatment due to ≥grade 3 AE (colitis). Prior treatment was documented: all 23 patients underwent surgical resection, 13 isolated limb perfusion (56.5%), 1 targeted therapy (4.3%), 2 immunotherapy (8.7%), 2 radiotherapy (8.7%). Prior treatment did not influence response or toxicity of T-VEC. PET-CT and biopsies proved to be a clinically useful tool to evaluate treatment response for T-VEC monotherapy, confirming pCR or PD to stage IV disease requiring systemic treatment.
ORR for T-VEC monotherapy at our institute was 82.6% with 52.2% achieving a CR. This prospective study for T-VEC in early metastatic (stage IIIB/C-IVM1a) melanoma demonstrated superior results to the phase 3 OPTiM study and confirms the role of oncolytic immunotherapy for melanoma.
Clinical trial identification
Legal entity responsible for the study
Alexander C.J. van Akkooi.
Has not received any funding.
V. Franke: Travel grant, Research funding: Amgen. A.C.J. van Akkooi: Honoraria: Amgen, Novartis, MSD/Merck; Travel cost: Amgen, Novartis, MSD/Merck. All other authors have declared no conflicts of interest.