Talimogene laherparepvec (T-VEC; IMLYGIC®, Amgen Inc.) is an oncolytic immunotherapy approved in Europe for the treatment of unresectable metastatic melanoma (stage IIIB-IVM1a). This study characterised real-world use of T-VEC in four European countries.
Data on demographics, treatment pattern, safety, and clinical effectiveness were examined in a retrospective chart review of patients with stage IIIB-IVM1a unresectable melanoma treated with T-VEC in surgical (the Netherlands) and medical (Austria, Germany, UK) oncology settings.
Overall, 66 patients were included (the Netherlands: n = 31; Austria, Germany, UK: n = 35). The median age was 69 years and 59.1% were female. At the time of T-VEC initiation, 47 patients (71.2%) had stage IIIB/C disease; of these, 30 were from the Netherlands. Although 72.7% patients overall received T-VEC as first-line therapy, this was higher in the Netherlands than the other countries (93.5% vs 54.3%). Of the 47 patients who discontinued T-VEC, 26 (55.3%) had no remaining injectable lesions (potentially indicating complete response); 20/26 of these patients were from the Netherlands. One patient discontinued T-VEC due to toxicity.
This study is the first comprehensive multinational evaluation of the use of T-VEC to treat unresectable stage IIIB/C-IVM1a melanoma in real-world clinical practice in Europe. The differences between European countries were apparent, with physicians in the Netherlands using T-VEC in patients with earlier advanced disease stage and in the first-line setting compared with other countries.

OBJECTIVE: Talimogene laherparepvec (T-VEC) is an intralesional therapy for unresectable, metastatic melanoma. T-VEC real-world use in the context of anti-PD1-based therapy requires further characterization.
METHODS: A retrospective review of T-VEC use from 1 January 2017 and 31 March 2018 for melanoma patients was conducted at seven US institutions.
RESULTS: Among 83 patients, three categories of T-VEC and anti-PD-1 therapy were identified: T-VEC used without anti-PD-1 (n = 29, 35%), T-VEC after anti-PD-1-based therapy (n = 22, 27%) and concurrent T-VEC and anti-PD-1-based therapy (n = 32, 39%). 25% of patients discontinued T-VEC therapy due to no remaining injectable lesions, 37% discontinued T-VEC due to progressive disease. Discontinuation of T-VEC did not differ by anti-PD-1-based therapy use or timing.
CONCLUSIONS: In real-world settings, T-VEC may be used concurrently with or after anti-PD-1-based therapy.

Aim: There is a growing body of data on real-world use of talimogene laherparepvec (T-VEC). We aimed to characterize real-world T-VEC use using a nationally representative German prescription database covering 60% of prescriptions reimbursed. Patients & methods: A retrospective analysis was conducted using the German IMS® LRx prescription database, analyzing patients aged ≥18 years with an initial T-VEC prescription at 106 plaque-forming units (PFU)/ml and ≥1 subsequent prescription at 108 PFU/ml. Median time on T-VEC treatment, patient characteristics and patterns of T-VEC use were described. Results: Of 127 patients prescribed T-VEC, 72 patients (57%) met study criteria. About two-thirds of these patients initiated T-VEC in 2017. Median age at T-VEC initiation was 74 years (range: 44 to 91). Most prescriptions (88%) were dispensed from hospitals. At study end, 26 (36%) patients remained on T-VEC; 46 (64%) had ended treatment. Median duration of T-VEC treatment for all patients was 18.7 weeks (95% CI: 15.3-26.9) and was longer among those who initiated treatment in 2017 versus 2016 (26.7 vs 15.6 weeks, respectively). Median volume administered for the first 106 PFU/ml and second 108 PFU/ml was 4 ml; the volume decreased for subsequent administrations (2 ml by the eighth administration and 1 ml by the 16th administration). Conclusion: This real-world prescription database study showed that patients who initiated treatment in 2017 had a treatment duration in clinical practice that corresponded with the European Summary of Product Characteristics guideline of continuing T-VEC for ≥6 months. Additional long-term data linking drug use with clinical outcomes are needed.

UNASSIGNED: Talimogene laherparepvec (T-VEC) is an intralesional treatment for unresectable cutaneous, subcutaneous and nodal melanoma. COSMUS-1 was conducted to examine how T-VEC is used in US clinical practice.
UNASSIGNED: A chart review was conducted at seven centers, with 78 patients screened and 76 eligible.
UNASSIGNED: Patients began treatment with T-VEC between October 2015 and December 2016. Median follow-up was 9.4 months. Twenty percent of patients (n = 15) completed T-VEC treatment with no remaining injectable lesions or pathologic complete response. Flu-like symptoms were the most commonly reported adverse events (n = 8; 10.5%), followed by lesion ulceration (n = 4; 5.3%). No herpetic lesions or infections were reported.
UNASSIGNED: T-VEC was well tolerated and showed clinical utility.

Oncolytic viruses selectively target and kill cancer cells in an immunogenic fashion, thus supporting the establishment of therapeutically relevant tumor-specific immune responses. In 2015, the US Food and Drug Administration (FDA) approved the oncolytic herpes simplex virus T-VEC for use in advanced melanoma patients. Since then, a plethora of trials has been initiated to assess the safety and efficacy of multiple oncolytic viruses in patients affected with various malignancies. Here, we summarize recent preclinical and clinical progress in the field of oncolytic virotherapy.

BACKGROUND: We previously reported that talimogene laherparepvec, an oncolytic herpes virus encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), resulted in an objective response rate of 26 % in patients with advanced melanoma in a phase II clinical trial. The response of individual lesions, however, was not reported. Since talimogene laherparepvec is thought to mediate anti-tumor activity through both direct tumor cytolysis and induction of systemic tumor-specific immunity, we sought to determine the independent response rate in virus-injected and non-injected lesions.
METHODS: Fifty patients with stage IIIC or IV melanoma were treated with talimogene laherparepvec in a multi-institutional single-arm open-label phase II clinical trial. In this study patients were treated until a complete response was achieved, all accessible tumors disappeared, clinically significant disease progression, or unacceptable toxicity. This report is a post hoc analysis of the systemic effects of talimogene laherparepvec in injected lesions and two types of uninjected lesions-non-visceral lesions and visceral lesions.
RESULTS: Eleven of 23 patients (47.8 %) had a ≥ 30 % reduction in the total burden of uninjected non-visceral lesions, and 2 of 12 patients (16.7 %) had a ≥ 30 % reduction in the total burden of visceral lesions. Among 128 evaluable lesions directly injected with talimogene laherparepvec, 86 (67.2 %) decreased in size by ≥ 30 % and 59 (46.1 %) completely resolved. Of 146 uninjected non-visceral lesions, 60 (41.1 %) decreased in size by ≥ 30 %, the majority of which (44 [30.1 %]) completely resolved. Of 32 visceral lesions, 4 (12.5 %) decreased in size by ≥ 30 %, and 3 (9.4 %) completely resolved. The median time to lesion response was shortest for lesions that were directly injected (18.4 weeks), followed by uninjected non-visceral lesions (23.1 weeks) and visceral lesions (51.3 weeks), consistent with initiation of a delayed regional and systemic anti-tumor immune response to talimogene laherparepvec.
CONCLUSIONS: These results support a regional and systemic effect of talimogene laherparepvec immunotherapy in patients with advanced melanoma.