title: Disease kinetics for decision-making in advanced melanoma: a call for scenario-driven strategy trials.
abstract: In the past 5 years, the treatment of metastatic melanoma has changed from almost no effective treatment to the use of targeted and immune therapies with proven improvements in survival. The time has now come to define the optimal drug combinations, sequence of treatment, and drug regimens (intermittent vs continuous dosing) in the treatment of patients with metastatic melanoma. In view of the prevalence of advanced melanoma, finite resources, and the heterogeneity of disease characteristics, not all possibilities can be tested in therapeutic trials starting from an unselected population of patients with metastatic melanoma. In practice, clinicians rely on a few clinically derived signals, especially dynamic signals, to categorise patients into scenarios, from fast disease kinetics to slow disease kinetics, which drive clinicians' therapeutic decision making. The realistic goals of therapy are different in each scenario. We recommend that these scenarios are incorporated into clinical trials as either patient inclusion criteria or stratification factors. This approach is not only feasible but is also the only way to generate evidence for more effective and individualised treatment strategies for patients with metastatic melanoma.
authors.affiliation: Aix-Marseille University and APHM Hospital CHU Timone, Marseille, France. Electronic address: jean-jacques.grob@ap-hm.fr.
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Grob
authors.affiliation: Melanoma Institute Australia, University of Sydney, and Mater Hospital, Sydney, NSW, Australia.
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
authors.affiliation: University Hospital Essen and German Cancer Consortium, Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Flaherty
mesh_terms: D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods*; D019091:Critical Pathways; D003661:Decision Support Techniques; D018450:Disease Progression; D006801:Humans; D007700:Kinetics; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D011237:Predictive Value of Tests; D011379:Prognosis; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology