Clinical Significance of Distant Metastasis-Free Survival (DMFS) in Melanoma: A Narrative Review from Adjuvant Clinical Trials

Abstract

Cutaneous melanoma is the most dangerous skin cancer, with high death rates in advanced stages. To assess the impact of each treatment on patient outcomes, most studies use relapse-free survival (RFS) as a primary endpoint and distant metastasis-free survival (DMFS) as a secondary endpoint. The aim of this narrative review of the main adjuvant studies for resected stage III/IV melanoma, with a specific focus on DMFS, is to evaluate DMFS trends and their potential association with RFS, identify which treatments are possibly associated with better outcomes in terms of DMFS and their potential predictive factors, and discuss DMFS trends in terms of patient management in daily practice. We outline the impact of each available treatment option on DMFS and RFS according to the years of follow-up and compare data from different studies. Overall, the trends of DMFS closely follow those of RFS, with most patients relapsing at visceral rather than regional sites. As it captures the burden of patients who develop distant relapse, DMFS could be considered a primary endpoint, in addition to RFS, in adjuvant trials, identifying patients whose relapse is associated with a worse prognosis and who may need further systemic treatment.

Explained variation and degrees of necessity and of sufficiency for competing risks survival data

“…In our reanalysis, we are interested in the role of prognostic factors for the occurrence of distant metastases (which also is nowadays considered the most clinically relevant end point; Amabile et al., 2021; Lambertini et al., 2020), taking into account death as a CE. Further recorded events, such as local recurrence, are ignored here.…”

Phenotypic and Dermoscopic Patterns of Familial Melanocytic Lesions: A Pilot Study in A Third-Level Center

“…Concurrent with rising incidence trends, the mortality rate in most of the world has been rising, yet the therapeutic landscape of unresectable stage III and IV melanoma has been recently revolutionized by immunotherapies and targeted therapies, which have markedly improved survival, compared to traditional chemotherapy regimens [9][10][11]. Similar to other cancers, melanoma has a multifactorial etiology, as its genesis results from the association of intrinsic and extrinsic risk factors [12,13]. Intrinsic (or constitutional) risk factors are represented by positive personal and/or family history, immunodepression, race, phototype, the presence of numerous and atypical nevi, and genetic mutations which are responsible for familial clusters of melanomas.…”

Visual symptoms in a patient treated with MEK inhibitors

“…1,2 This combined targeted therapy acts by inhibiting the proliferative pathway induced by an altered protein encoded by the BRAF gene, found in approximately 50 − 60% of melanoma patients, which provides the tumour with an externally independent proliferative stimulus. 3 Overall, these drugs are well tolerated, with mild to moderate toxicities which can be generally handled rapidly. 3 As for MEK inhibitors, such as Trametinib, Cobimetinib and Binimetinib, the association with subretinal fluid (SRF) accumulation has been documented and its relatively benign nature has been described in the literature.…”

“…3 Overall, these drugs are well tolerated, with mild to moderate toxicities which can be generally handled rapidly. 3 As for MEK inhibitors, such as Trametinib, Cobimetinib and Binimetinib, the association with subretinal fluid (SRF) accumulation has been documented and its relatively benign nature has been described in the literature. 4,5 Herein, we describe the uncommon development of intermittent visual symptoms, with and without concomitant funduscopic and OCT findings, in a patient treated with MEK inhibitors.…”