ESMO consensus conference recommendations on the management of locoregional melanoma: under the auspices of the ESMO Guidelines Committee

Abstract

The European Society for Medical Oncology (ESMO) held a consensus conference on melanoma on 5e7 September 2019 in Amsterdam, The Netherlands. The conference included a multidisciplinary panel of 32 leading experts in the management of melanoma. The aim of the conference was to develop recommendations on topics that are not covered in detail in the current ESMO Clinical Practice Guideline and where available evidence is either limited or conflicting. The main topics identified for discussion were: (i) the management of locoregional disease; (ii) targeted versus immunotherapies in the adjuvant setting; (iii) targeted versus immunotherapies for the first-line treatment of metastatic melanoma; (iv) when to stop immunotherapy or targeted therapy in the metastatic setting; and (v) systemic versus local treatment of brain metastases. The expert panel was divided into five working groups in order to each address questions relating to one of the five topics outlined above. Relevant scientific literature was reviewed in advance. Recommendations were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the results relating to the management of locoregional melanoma, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation. All participants approved the final manuscript.

How we treat locoregional melanoma

“…Few trials specifically addressed the treatment of these lesions, but radical surgery can be considered in cases of few, small, and nonrapidly recurrent lesions. 8 By contrast, bulky lesions belonging to this category must be treated with systemic therapy (stage III inoperable). An additional type of therapy such as talimogene laherparepvec (T-VEC), PV-10, and regional chemotherapy has shown moderate efficacy in several trials but must to be practiced only in experienced centers.…”

Molecular Aspects of the Isolated Limb Infusion Procedure

“…These measures, and the mild hyperthermia, improve the take up of the cytotoxic agents by the exposed tissues, augmenting tumour responses. In case locally advanced melanomas or sarcomas are confined to a limb, these patients can often be effectively treated by high-dose loco-regional chemotherapy administered by either hyperthermic isolated limb perfusion (HILP) or isolated limb infusion (ILI), although these procedures are not uniformly recommended by current American, European and Australian guidelines [1,[4][5][6][7][8][9][10][11]. Both HILP and ILI are well-established treatments in the neoadjuvant setting to improve resectability for sarcoma, as well as an adjuvant or palliative treatment when melanoma ITMs or local recurrences of sarcoma are present.…”

Applying adjuvant therapy for melanoma into clinical practice

“…There are no direct comparator studies of these two approaches in the adjuvant setting. The European Society of Medical Oncology (ESMO) consensus conference recommendations compare the results from the Keynote-054 and COMBI-AD trials, as these have similar study populations and were conducted at similar times [16]. Treatment with 12 months of targeted therapy has a proven RFS benefit and a suggestion of an OS benefit in the adjuvant setting, although this didn't meet pre-specified P value for significance [10].…”

“…Given that the risk of further (distant) recurrence is high and that there is no evidence to suggest that patients become cross-resistant to both targeted and immunotherapies, BRAF mutant patients who recur despite one therapy should be considered for the alternative 'second adjuvant' therapy (e.g. initial immunotherapy, subsequent targeted therapy) [16,20].…”