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

• Published in: Cancers 2022-11, Vol.14 (22), p.5694
• Main Authors: Rauwerdink, Daan Jan Willem, van Doorn, Remco, van der Hage, Jos, Van den Eertwegh, Alfonsus J M, Haanen, John B A G, Aarts, Maureen, Berkmortel, Franchette, Blank, Christian U, Boers-Sonderen, Marye J, De Groot, Jan Willem B, Hospers, Geke A P, de Meza, Melissa, Piersma, Djura, Van Rijn, Rozemarijn S, Stevense, Marion, Van der Veldt, Astrid, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn, van der Kooij, Monique, Kapiteijn, Ellen
• Format: Article
• Language: English
• Subjects: CTLA-4 protein; Diagnosis; Immunotherapy; Invasiveness; MEK inhibitors; Melanoma; Metastases; Metastasis; Mutation; Patients; PD-1 protein; Satellites; Survival
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14225694

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.