1. Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma
- Author
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Isabella A. J. van Duin, Sjoerd G. Elias, Alfonsus J. M. van den Eertwegh, Jan Willem B. de Groot, Willeke A. M. Blokx, Paul J. van Diest, Tim Leiner, Joost J. C. Verhoeff, Rik J. Verheijden, Olivier J. van Not, Maureen J. B. Aarts, Franchette W. P. J. van den Berkmortel, Christian U. Blank, John B. A. G. Haanen, Geke A. P. Hospers, Anna M. Kamphuis, Djura Piersma, Rozemarijn S. van Rijn, Astrid A. M. van der Veldt, Gerard Vreugdenhil, Michel W. J. M. Wouters, Marion A. M. Stevense‐den Boer, Marye J. Boers‐Sonderen, Ellen Kapiteijn, Karijn P. M. Suijkerbuijk, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), Internal medicine, Medical oncology, AII - Cancer immunology, CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), and Radiology & Nuclear Medicine
- Subjects
Mitogen-Activated Protein Kinase Kinases ,Cancer Research ,Oncology ,Antineoplastic Combined Chemotherapy Protocols/adverse effects ,Proto-Oncogene Proteins B-raf/genetics ,BRAF(/MEK) inhibition ,melanoma ,SURVIVAL ,Humans ,immune checkpoint inhibition ,immunotherapy ,prognosis ,Retrospective Studies - Abstract
Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune-surveillance. We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing first-line systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression-free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti-PD-1-based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI-treated patients with a TFDR 5 years (P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR 5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first-line ICI or targeted therapy.
- Published
- 2023
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