title: Systematic review of the use of granulocyte-macrophage colony-stimulating factor in patients with advanced melanoma.
abstract: Several immunomodulatory checkpoint inhibitors have been approved for the treatment of patients with advanced melanoma, including ipilimumab, nivolumab and pembrolizumab. Talimogene laherparepvec is the first oncolytic virus to gain regulatory approval in the USA; it is also approved in Europe. Talimogene laherparepvec expresses granulocyte-macrophage colony-stimulating factor (GM-CSF), and with other GM-CSF-expressing oncolytic viruses in development, understanding the clinical relevance of this cytokine in treating advanced melanoma is important. Results of trials of GM-CSF in melanoma have been mixed, and while GM-CSF has the potential to promote anti-tumor responses, some preclinical data suggest that GM-CSF may sometimes promote tumor growth. GM-CSF has not been approved as a melanoma treatment. We undertook a systematic literature review of studies of GM-CSF in patients with advanced melanoma (stage IIIB-IV). Of the 503 articles identified, 26 studies met the eligibility criteria. Most studies investigated the use of GM-CSF in combination with another treatment, such as peptide vaccines or chemotherapy, or as an adjuvant to surgery. Some clinical benefit was reported in patients who received GM-CSF as an adjuvant to surgery, or in combination with other treatments. In general, outcomes for patients receiving peptide vaccines were not improved with the addition of GM-CSF. GM-CSF may be a valuable therapeutic adjuvant; however, further studies are needed, particularly head-to-head comparisons, to confirm the optimal dosing regimen and clinical effectiveness in patients with advanced melanoma.
authors.affiliation: Department of Dermatology, Medical University Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. christoph.hoeller@meduniwien.ac.at.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hoeller
authors.affiliation: Department of Oncology, Lausanne University Hospital, Champ de l'Air, Rue du Bugnon 21, 1011, Lausanne, Switzerland.|Ludwig Centre and Swiss Institute of Bioinformatics, Génopode Building, 1015, Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Michielin
authors.affiliation: Istituto Nazionale Tumori, Fondazione 'G. Pascale', Via Mariano Semmola, 52, 80131, Naples, Italy.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.affiliation: Clinical Development, Amgen Europe GmbH, Dammstrasse 23, 6300, Zug, Switzerland.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szabo
authors.affiliation: Division of Immunology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands.
authors.forename: Christian U
authors.initials: CU
authors.lastname: Blank
mesh_terms: D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Efficacy; GM-CSF; Granulocyte–macrophage colony-stimulating factor; Immunotherapy; Melanoma