Systemic Therapy in Advanced Nodular Melanoma versus Superficial Spreading Melanoma: A Nation-Wide Study of the Dutch Melanoma Treatment Registry

Daan Jan Willem Rauwerdink*, Remco van Doorn, Jos van der Hage, Alfonsus J M Van den Eertwegh, John B A G Haanen, Maureen Aarts, Franchette Berkmortel, Christian U Blank, Marye J Boers-Sonderen, Jan Willem B De Groot, Geke A P Hospers, Melissa de Meza, Djura Piersma, Rozemarijn S Van Rijn, Marion Stevense, Astrid Van der Veldt, Gerard Vreugdenhil, Michel W J M Wouters, Karijn Suijkerbuijk, Monique van der KooijEllen Kapiteijn

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Nodular melanoma (NM) is associated with a higher locoregional and distant recurrence rate compared with superficial spreading melanoma (SSM); it is unknown whether the efficacy of systemic therapy is limited. Here, we compare the efficacy of immunotherapy and BRAF/MEK inhibitors (BRAF/MEKi) in advanced NM to SSM. Patients with advanced stage IIIc and stage IV NM and SSM treated with anti-CTLA-4 and/or anti-PD-1, or BRAF/MEKi in the first line, were included from the prospective Dutch Melanoma Treatment Registry. The primary objectives were distant metastasis-free survival (DMFS) and overall survival (OS). In total, 1086 NM and 2246 SSM patients were included. DMFS was significantly shorter for advanced NM patients at 1.9 years (CI 95% 0.7–4.2) compared with SSM patients at 3.1 years (CI 95% 1.3–6.2) (p < 0.01). Multivariate survival analysis for immunotherapy and BRAF/MEKi demonstrated a hazard ratio for immunotherapy of 1.0 (CI 95% 0.85–1.17) and BRAF/MEKi of 0.95 (CI 95% 0.81–1.11). A shorter DMFS for NM patients developing advanced disease compared with SSM patients was observed, while no difference was observed in the efficacy of systemic immunotherapy or BRAF/MEKi between NM and SSM patients. Our results suggests that the worse overall survival of NM is mainly driven by propensity of metastatic outgrowth of NM after primary diagnosis.

Original languageEnglish
Article number5694
Issue number22
Publication statusPublished - 19 Nov 2022

Bibliographical note

For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical
Auditing foundation received a start-up grant from governmental organization The Netherlands
Organization for Health Research and Development (ZonMW, project number 836002002). The
DMTR is structurally funded by Bristol Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche
Pharma. Roche Pharma stopped funding in 2019, and Pierre Fabre started funding the DMTR in 2019.
For this work, no funding was granted.

Publisher Copyright:
© 2022 by the authors.


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