Current and emerging opportunities for deintensification of systemic therapies in melanoma: A scoping review

There is growing interest in optimising melanoma management to reduce over-treatment and improve patient safety and quality-of-life, yet clinical guidance on deintensification is minimal. This scoping review characterises the role of systemic therapies and biomarkers in current and emerging melanoma deintensification strategies. Study types, funding sources, and use of patient-reported outcomes (PRO) were also summarised.

MEDLINE, EMBASE and PubMed searches identified studies on deintensification in adult patients with cutaneous melanoma (January 2013 to June 2023). Additional texts were sourced via Google Scholar and backward citation searches. Three extraction tools were tailored to accommodate the breadth of articles included: A) deintensification approaches including biomarkers in late-phase development; B) non-systematic reviews; and C) early-phase biomarkers. Screening and data extraction were performed by two reviewers using Covidence. Data were analysed using descriptive statistics with results reported as per PRISMA-ScR guidelines.

Of 3721 articles screened, 301 articles were included: 31 non-systematic reviews, 198 early-phase biomarker studies, and 72 studies on deintensification approaches. Five key approaches emerged: shortened duration of therapy, dose attenuation, biomarker-informed, neoadjuvant and/or response-adapted, and miscellaneous. Most data were retrospective; only five randomised controlled trials were included in Category A (two were trial protocols). Early-phase biomarker studies comprised 66 % (n = 198/301) of articles - few progressed to trials of clinical validation/utility. PRO were reported in 11 % (n = 5/45) of Category A studies.

Shortened duration of anti-PD-1 therapy and neoadjuvant approaches hold substantial promise in deintensification. Future trials should prioritise consistent incorporation of PRO and focus on determining clinical utility of biomarkers.