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Introduction: 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., Methods: 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., Results: 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., Conclusion: 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.

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 December 2016, 48 eligible patients started treatment at the Netherlands Cancer Institute. We included 26 patients in this study with a follow up time ≥6 months, reporting Overall Response Rate (ORR), Disease Control Rate (DCR), Adverse Events (AE), prior treatment for melanoma and baseline characteristics, documented in a prospectively maintained database. In house developed treatment protocol consists of clinical evaluation, periodic PET-CT and histological biopsies for response evaluation. Median follow-up was 12.5 months. Of 26 patients, 16 (61.5%) had a Complete Response (CR) as their best response. Seven (26.9%) patients had a Partial Response (PR) as their best response, 1 (3.8%) patient Stable Disease (SD) and 2 (7.7%) patients Progressive Disease (PD). Best ORR was 88.5%. DCR was 92.3%. Grade 1-2 AEs occurred in all patients. Mostly, these consisted of fatigue, influenza-like symptoms and injection site erythema. All patients underwent prior treatment. Prior treatment did not influence response or toxicity of T-VEC. Best ORR for T-VEC monotherapy at our institute was 88.5% with 61.5% 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., (© 2019 UICC.)

Background: Non-sentinel node (NSN) positivity impacts the prognosis of melanoma patients; however, the benefits of completion lymph node dissection in patients with positive sentinel nodes (SNs) are limited., Objective: We aimed to present a predictive nomogram for NSN positivity in melanoma patients with a positive SN biopsy., Methods: This retrospective analysis from patients who underwent SN biopsy in a Brazilian institution from 2000 to 2015 was used for the construction and internal validation of the nomogram. This nomogram was then externally validated in a cohort of Dutch patients., Results: The Brazilian cohort comprised 1213 patients, with a mean follow-up of 5.11 years. Breslow thickness (odds ratio [OR] 1.170, 95% confidence interval [CI] 1.043-1.314]; p = 0.008), number of positive SNs (OR 1.092, 95% CI 1.034-1.153; p = 0.001), and largest diameter of the metastatic deposit (OR 3.217, 95% CI 1.551-6.674; p = 0.002) were statistically significant for NSN positivity. Internal validation was performed using a bootstrapping technique. A good performance was observed (Brier score 0.097) and an excellent power of discrimination was achieved (area under the curve [AUC] 0.822). The nomogram was then applied to the Dutch cohort, and its overall performance (Brier score 0.085), calibration (Hosmer-Lemeshow goodness-of-fit test; p = 0.198), and discriminatory power (AUC 0.752, 95% CI 0.615-0.890) were all adequate., Conclusions: We presented a nomogram for assessing NSN probability that should not only be used for surgical considerations but also for risk stratification and clinical decisions. Internal validation has shown that this is an adequate model, while external validation increases the model's reliability and suggests that it can be globally incorporated.